Cell death is one of the most important mechanisms of maintaining homeostasis in our body. Ferroptosis and pyroptosis are forms of necrosis-like cell death. These cell death modalities play key roles in the pathophysiology of cancer, cardiovascular, neurological diseases, and other pathologies. Transition metals are abundant group of elements in all living organisms. This paper presents a summary of ferroptosis and pyroptosis pathways and their connection to significant transition metals, namely zinc (Zn), copper (Cu), molybdenum (Mo), lead (Pb), cobalt (Co), iron (Fe), cadmium (Cd), nickel (Ni), mercury (Hg), uranium (U), platinum (Pt), and one crucial element, selenium (Se). Authors aim to summarize the up-to-date knowledge of this topic.In this review, there are categorized and highlighted the most common patterns in the alterations of ferroptosis and pyroptosis by transition metals. Special attention is given to zinc since collected data support its dual nature of action in both ferroptosis and pyroptosis. All findings are presented together with a brief description of major biochemical pathways involving mentioned metals and are visualized in attached comprehensive figures.This work concludes that the majority of disruptions in the studied metals' homeostasis impacts cell fate, influencing both death and survival of cells in the complex system of altered pathways. Therefore, this summary opens up the space for further research.

1st Faculty of Medicine BIOCEV Charles University Prumyslova 595 Vestec CZ 252 50 Czech Republic

Department of Pathological Physiology Faculty of Medicine Masaryk University Kamenice 5 Brno CZ 625 00 Czech Republic

Department of Physiology Faculty of Medicine Masaryk University Kamenice 5 Brno CZ 625 00 Czech Republic

Regional Centre for Applied Molecular Oncology Masaryk Memorial Cancer Institute Zluty kopec 7 Brno 656 53 Czech Republic

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Dolma S, Lessnick SL, Hahn WC, Stockwell BR. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell. 2003;3(3):285–96. 10.1016/S1535-6108(03)00050-3 PubMed DOI

Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–72. 10.1016/j.cell.2012.03.042 PubMed DOI PMC

Gao M, Jiang X. To eat or not to eat-the metabolic flavor of ferroptosis. Curr Opin Cell Biol. 2018;51:58–64. 10.1016/j.ceb.2017.11.001 PubMed DOI PMC

Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, et al. Ferroptosis: a regulated cell death Nexus linking metabolism, Redox Biology, and Disease. Cell. 2017;171(2):273–85. 10.1016/j.cell.2017.09.021 PubMed DOI PMC

Kuang F, Liu J, Tang D, Kang R. Oxidative damage and antioxidant defense in Ferroptosis. Front Cell Dev Biology. 2020;8. PubMed PMC

Ward JPT. From physiological Redox Signalling to oxidant stress. Adv Exp Med Biol. 2017;967:335–42. PubMed

Chen X, Li J, Kang R, Klionsky DJ, Tang D. Ferroptosis: machinery and regulation. Autophagy. 2021;17(9):2054–81. 10.1080/15548627.2020.1810918 PubMed DOI PMC

Shintoku R, Takigawa Y, Yamada K, Kubota C, Yoshimoto Y, Takeuchi T, et al. Lipoxygenase-mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3. Cancer Sci. 2017;108(11):2187–94. 10.1111/cas.13380 PubMed DOI PMC

Yuan H, Li X, Zhang X, Kang R, Tang D. Identification of ACSL4 as a biomarker and contributor of ferroptosis. Biochem Biophys Res Commun. 2016;478(3):1338–43. 10.1016/j.bbrc.2016.08.124 PubMed DOI

Doll S, Proneth B, Tyurina YY, Panzilius E, Kobayashi S, Ingold I, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol. 2017;13(1):91–8. 10.1038/nchembio.2239 PubMed DOI PMC

Hsieh H, Vignesh KS, Deepe GS, Choubey D, Shertzer HG, Genter MB. Mechanistic studies of the toxicity of zinc gluconate in the olfactory neuronal cell line Odora. Toxicol vitro: Int J Published Association BIBRA. 2016;35:24–30.10.1016/j.tiv.2016.05.003 PubMed DOI PMC

Wang H, Liu C, Zhao YX, Gao G. Mitochondria regulation in ferroptosis. Eur J Cell Biol. 2020;99(1). PubMed

Gao M, Yi J, Zhu J, Minikes AM, Monian P, Thompson CB, et al. Role of Mitochondria in Ferroptosis. Mol Cell. 2019;73(2):354–e633. 10.1016/j.molcel.2018.10.042 PubMed DOI PMC

Gaschler MM, Hu F, Feng H, Linkermann A, Min W, Stockwell BR. Determination of the Subcellular Localization and Mechanism of Action of Ferrostatins in suppressing ferroptosis. ACS Chem Biol. 2018;13(4):1013–20. 10.1021/acschembio.8b00199 PubMed DOI PMC

Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ, et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol. 2014;2014 16(12):12. PubMed PMC

Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009;417(Pt 1):1. 10.1042/BJ20081386 PubMed DOI PMC

Liu Ye, Lu S, Wu Ll, Yang L, Yang L, Wang J. The diversified role of mitochondria in ferroptosis in cancer. Cell Death Disease 2023. 2023;14(8):8. PubMed PMC

Gao M, Monian P, Quadri N, Ramasamy R, Jiang X. Glutaminolysis and transferrin regulate Ferroptosis. Mol Cell. 2015;59(2):298. 10.1016/j.molcel.2015.06.011 PubMed DOI PMC

Murphy TH, Miyamoto M, Sastre A, Schnaar RL, Coyle JT. Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. Neuron. 1989;2(6):1547–58. 10.1016/0896-6273(89)90043-3 PubMed DOI

Shirlee Tan BSP, David Schubert BSP, Pamela Maher BSP, Oxytosis. A novel form of programmed cell death. Curr Top Med Chem. 2001;1(6):497–506. 10.2174/1568026013394741 PubMed DOI

Hirschhorn T, Stockwell BR. The development of the concept of ferroptosis. Free Radic Biol Med. 2019;133:130–43. 10.1016/j.freeradbiomed.2018.09.043 PubMed DOI PMC

Enke U, Seyfarth L, Schleussner E, Markert UR. Impact of PUFA on early immune and fetal development. Br J Nutr. 2008;100(6):1158–68. 10.1017/S000711450801413X PubMed DOI

Matsushita M, Freigang S, Schneider C, Conrad M, Bornkamm GW, Kopf M. T cell lipid peroxidation induces ferroptosis and prevents immunity to infection. J Exp Med. 2015;212(4):555–68. 10.1084/jem.20140857 PubMed DOI PMC

Gujja P, Rosing DR, Tripodi DJ, Shizukuda Y. Iron overload cardiomyopathy: better understanding of an increasing disorder. J Am Coll Cardiol. 2010;56(13):1001–12. 10.1016/j.jacc.2010.03.083 PubMed DOI PMC

Yuan H, Pratte J, Giardina C. Ferroptosis and its potential as a therapeutic target. Biochem Pharmacol. 2021;186:114486. 10.1016/j.bcp.2021.114486 PubMed DOI

Zhang Y, Sun C, Zhao C, Hao J, Zhang Y, Fan B, et al. Ferroptosis inhibitor SRS 16–86 attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury. Brain Res. 2019;1706:48–57. 10.1016/j.brainres.2018.10.023 PubMed DOI

Magtanong L, Dixon SJ. Ferroptosis and Brain Injury. Dev Neurosci. 2018;40(5–6):382–95. 10.1159/000496922 PubMed DOI PMC

Cassier-Chauvat C, Marceau F, Farci S, Ouchane S, Chauvat F. The glutathione system: a journey from Cyanobacteria to higher eukaryotes. Antioxid (Basel). 2023;12(6). PubMed PMC

Tan M, Yin Y, Ma X, Zhang J, Pan W, Tan M, et al. Glutathione system enhancement for cardiac protection: pharmacological options against oxidative stress and ferroptosis. Cell Death Dis. 2023;14(2):131. 10.1038/s41419-023-05645-y PubMed DOI PMC

Bao WD, Pang P, Zhou XT, Hu F, Xiong W, Chen K, et al. Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer’s disease. Cell Death Differ. 2021;28(5):1548–62. 10.1038/s41418-020-00685-9 PubMed DOI PMC

Zhao Y, Liu Y, Xu Y, Li K, Zhou L, Qiao H, et al. The role of ferroptosis in blood–brain barrier Injury. Cell Mol Neurobiol. 2023;43(1):223–36. 10.1007/s10571-022-01197-5 PubMed DOI

Xu Y, Li K, Zhao Y, Zhou L, Liu Y, Zhao J. Role of ferroptosis in stroke. Cell Mol Neurobiol. 2023;43(1):205–22. 10.1007/s10571-022-01196-6 PubMed DOI

Tian X, Li X, Pan M, Yang LZ, Li Y, Fang W. Progress of ferroptosis in ischemic stroke and therapeutic targets. Cell Mol Neurobiol. 2024;44(1):25. 10.1007/s10571-024-01457-6 PubMed DOI PMC

Lei G, Zhuang L, Gan B. Targeting ferroptosis as a vulnerability in cancer. Nat Rev Cancer. 2022;22(7):381–96. 10.1038/s41568-022-00459-0 PubMed DOI PMC

Feng S, Tang D, Wang Y, Li X, Bao H, Tang C, et al. The mechanism of ferroptosis and its related diseases. Mol Biomed. 2023;4(1):33. 10.1186/s43556-023-00142-2 PubMed DOI PMC

Siegel RM. Caspases at the crossroads of immune-cell life and death. Nat Rev Immunol. 2006;6(4):308–17. 10.1038/nri1809 PubMed DOI

Man SM, Karki R, Kanneganti TD. Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunol Rev. 2017;277(1):61–75. 10.1111/imr.12534 PubMed DOI PMC

Brennan MA, Cookson BT. Salmonella induces macrophage death by caspase-1-dependent necrosis. Mol Microbiol. 2000;38(1):31–40. 10.1046/j.1365-2958.2000.02103.x PubMed DOI

Zychlinsky A, Prevost MC, Sansonetti PJ. Shigella flexneri induces apoptosis in infected macrophages. Nature. 1992;358(6382):167–9. 10.1038/358167a0 PubMed DOI

Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Reviews Immunol 2013. 2013;13(6):6. PubMed PMC

Lamkanfi M, Dixit VM. Mechanisms and functions of inflammasomes. Cell. 2014;157(5):1013–22. 10.1016/j.cell.2014.04.007 PubMed DOI

Rathinam VAK, Fitzgerald KA. Inflammasome complexes: emerging mechanisms and Effector functions. Cell. 2016;165(4):792–800. 10.1016/j.cell.2016.03.046 PubMed DOI PMC

Man SM, Hopkins LJ, Nugent E, Cox S, Glück IM, Tourlomousis P, et al. Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macromolecular complex. Proc Natl Acad Sci USA. 2014;111(20):7403–8. 10.1073/pnas.1402911111 PubMed DOI PMC

Liu S, Du J, Li D, Yang P, Kou Y, Li C, et al. Oxidative stress induced pyroptosis leads to osteogenic dysfunction of MG63 cells. J Mol Histol. 2020;51(3):221–32. 10.1007/s10735-020-09874-9 PubMed DOI

Zhou B, Zhang J, Xs L, Hz C, Yl A, Cheng K, et al. Tom20 senses iron-activated ROS signaling to promote melanoma cell pyroptosis. Cell Res. 2018;28(12):1171–85. 10.1038/s41422-018-0090-y PubMed DOI PMC

Zhao C, Yu D, He Z, Bao L, Feng L, Chen L, et al. Endoplasmic reticulum stress-mediated autophagy activation is involved in cadmium-induced ferroptosis of renal tubular epithelial cells. Free Radic Biol Med. 2021;175:236–48. 10.1016/j.freeradbiomed.2021.09.008 PubMed DOI

Shen B, Mei M, Ai S, Liao X, Li N, Xiang S et al. TRPC6 inhibits renal tubular epithelial cell pyroptosis through regulating zinc influx and alleviates renal ischemia-reperfusion injury. FASEB Journal: Official Publication Federation Am Soc Experimental Biology. 2022;36(10). PubMed

Gu X, Wang Y, He Y, Zhao B, Zhang Q, Li S. MiR-1656 targets GPX4 to trigger pyroptosis in broilers kidney tissues by activating NLRP3 inflammasome under Se deficiency. J Nutr Biochem. 2022;105. PubMed

Liao J, Hu Z, Li Q, Li H, Chen W, Huo H, et al. Endoplasmic reticulum stress contributes to Copper-Induced pyroptosis via regulating the IRE1α-XBP1 pathway in Pig Jejunal epithelial cells. J Agric Food Chem. 2022;70(4):1293–303. 10.1021/acs.jafc.1c07927 PubMed DOI

Pi S, Nie G, Wei Z, Yang F, Wang C, Xing C, et al. Inhibition of ROS/NLRP3/Caspase-1 mediated pyroptosis alleviates excess molybdenum-induced apoptosis in duck renal tubular epithelial cells. Ecotoxicol Environ Saf. 2021;208:111528. 10.1016/j.ecoenv.2020.111528 PubMed DOI

Yan H, Luo B, Wu X, Guan F, Yu X, Zhao L, et al. Cisplatin induces pyroptosis via activation of MEG3/NLRP3/caspase-1/GSDMD pathway in Triple-negative breast Cancer. Int J Biol Sci. 2021;17(10):2606. 10.7150/ijbs.60292 PubMed DOI PMC

Li Y, Xia W, Wu M, Yin J, Wang Q, Li S, et al. Activation of GSDMD contributes to acute kidney injury induced by cisplatin. Am J Physiol - Ren Physiol. 2020;318(1):F96–106.10.1152/ajprenal.00351.2019 PubMed DOI

Li RY, Zheng ZY, Li ZM, Heng JH, Zheng YQ, Deng DX et al. Cisplatin-induced pyroptosis is mediated via the CAPN1/CAPN2-BAK/BAX-caspase-9-caspase-3-GSDME axis in esophageal cancer. Chemico-Biol Interact. 2022;361. PubMed

Zhang Cc L, Cg W, Yf X, Lh H, Xh Z, Qz, et al. Chemotherapeutic paclitaxel and cisplatin differentially induce pyroptosis in A549 lung cancer cells via caspase-3/GSDME activation. Apoptosis. 2019;24(3–4):312–25. 10.1007/s10495-019-01515-1 PubMed DOI

Yu J, Li S, Qi J, Chen Z, Wu Y, Guo J et al. Cleavage of GSDME by caspase-3 determines lobaplatin-induced pyroptosis in colon cancer cells. Cell Death Dis. 2019;10(3). PubMed PMC

Chen J, Ge L, Shi X, Liu J, Ruan H, Heng D, et al. Lobaplatin induces pyroptosis in Cervical Cancer cells via the Caspase-3/GSDME Pathway. Anti-cancer Agents Med Chem. 2022;22(11):2091–7.10.2174/1871520621666211018100532 PubMed DOI

Chen ZD, Xu G, Wu D, Wu SH, Gong L, Li ZH et al. Lobaplatin induces pyroptosis through regulating cIAP1/2, Ripoptosome and ROS in nasopharyngeal carcinoma. Biochem Pharmacol. 2020;177. PubMed

Tang J, Bei M, Zhu J, Xu G, Chen D, Jin X et al. Acute cadmium exposure induces GSDME-mediated pyroptosis in triple-negative breast cancer cells through ROS generation and NLRP3 inflammasome pathway activation. Environ Toxicol Pharmacol. 2021;87. PubMed

Long Y, Liu X, Xz T, Cx J, Sw C. ROS-induced NLRP3 inflammasome priming and activation mediate PCB 118- induced pyroptosis in endothelial cells. Ecotoxicol Environ Saf. 2020;189:109937. 10.1016/j.ecoenv.2019.109937 PubMed DOI

Fang Y, Tian S, Pan Y, Li W, Wang Q, Tang Y, et al. Pyroptosis: a new frontier in cancer. Volume 121. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie; 2020. PubMed

Murao A, Aziz M, Wang H, Brenner M, Wang P. Release mechanisms of major DAMPs. Apoptosis. 2021;26(3):152. 10.1007/s10495-021-01663-3 PubMed DOI PMC

Zindel J, Kubes P. DAMPs, PAMPs, and LAMPs in immunity and sterile inflammation. Annu Rev Pathol. 2020;15:493–518. 10.1146/annurev-pathmechdis-012419-032847 PubMed DOI

Miao EA, Rajan JV, Aderem A. Caspase-1-induced pyroptotic cell death. Immunol Rev. 2011;243(1):206–14. 10.1111/j.1600-065X.2011.01044.x PubMed DOI PMC

Jorgensen I, Rayamajhi M, Miao EA. Programmed cell death as a defence against infection. Nat Reviews Immunol 2017. 2017;17(3):3. PubMed PMC

Ranson N, Kunde D, Eri R. Regulation and sensing of inflammasomes and their impact on Intestinal Health. Int J Mol Sci. 2017;18(11). PubMed PMC

Nagata S, Tanaka M. Programmed cell death and the immune system. Nat Reviews Immunol 2017. 2017;17(5):5. PubMed

An J, Kim SY, Yang EG, Chung HS. A fluorescence-polarization-based lipopolysaccharide-Caspase-4 Interaction Assay for the development of inhibitors. Molecules. 2022;27(8). PubMed PMC

Hu L, Chen M, Chen X, Zhao C, Fang Z, Wang H et al. Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate. Cell Death & Disease 2020 11:4. 2020;11(4):1–17. PubMed PMC

Kostura MJ, Tocci MJ, Limjuco G, Chin J, Cameron P, Hillman AG, et al. Identification of a monocyte specific pre-interleukin 1 beta convertase activity. Proc Natl Acad Sci USA. 1989;86(14):5227–31. 10.1073/pnas.86.14.5227 PubMed DOI PMC

Black RA, Kronheim SR, Sleath PR. Activation of interleukin-1 beta by a co-induced protease. FEBS Lett. 1989;247(2):386–90. 10.1016/0014-5793(89)81376-6 PubMed DOI

Ghayur T, Banerjee S, Hugunin M, Butler D, Herzog L, Carter A, et al. Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production. Nature. 1997;386(6625):619–23. 10.1038/386619a0 PubMed DOI

Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, et al. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature. 1992;356(6372):768–74. 10.1038/356768a0 PubMed DOI

Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H, et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nat 2016. 2016;535(7610):7610. PubMed PMC

Aglietti RA, Estevez A, Gupta A, Ramirez MG, Liu PS, Kayagaki N, et al. GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes. Proc Natl Acad Sci USA. 2016;113(28):7858–63. 10.1073/pnas.1607769113 PubMed DOI PMC

Chen X, He WT, Hu L, Li J, Fang Y, Wang X, et al. Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis. Cell Res 2016. 2016;26(9):9. PubMed PMC

Ding J, Wang K, Liu W, She Y, Sun Q, Shi J, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature. 2016;535(7610):111–6. 10.1038/nature18590 PubMed DOI

Kovacs SB, Miao EA, Gasdermins. Effectors of Pyroptosis. Trends Cell Biol. 2017;27(9):673–84. 10.1016/j.tcb.2017.05.005 PubMed DOI PMC

Lemasters JJ. Molecular mechanisms of cell death. Essent Concepts Mol Pathol. 2020.

Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the nomenclature Committee on Cell Death 2018. Cell Death Differ 2018. 2018;25(3):3. PubMed PMC

Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nat Reviews Immunol 2016. 2016;16(7):7. PubMed

Rogers C, Fernandes-Alnemri T, Mayes L, Alnemri D, Cingolani G, Alnemri ES. Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death. Nat Commun. 2017;8. PubMed PMC

Wang Y, Yin B, Li D, Wang G, Han X, Sun X. GSDME mediates caspase-3-dependent pyroptosis in gastric cancer. Biochem Biophys Res Commun. 2018;495(1):1418–25. 10.1016/j.bbrc.2017.11.156 PubMed DOI

Jiang M, Qi L, Li L, Li Y. The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer. Cell Death Discovery 2020. 2020;6(1):1. PubMed PMC

Taabazuing CY, Okondo MC, Bachovchin DA. Pyroptosis and apoptosis pathways engage in bidirectional crosstalk in Monocytes and macrophages. Cell Chem Biology. 2017;24(4):507–e144.10.1016/j.chembiol.2017.03.009 PubMed DOI PMC

Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol. 2009;27:229–65. 10.1146/annurev.immunol.021908.132715 PubMed DOI

Harijith A, Ebenezer DL, Natarajan V. Reactive oxygen species at the crossroads of inflammasome and inflammation. Front Physiol. 2014;0:352. PubMed PMC

Cridland JA, Curley EZ, Wykes MN, Schroder K, Sweet MJ, Roberts TL et al. The mammalian PYHIN gene family: phylogeny, evolution and expression. BMC Evol Biol. 2012;12(1). PubMed PMC

Bosso M, Kirchhoff F. Emerging role of PYHIN Proteins as antiviral restriction factors. Viruses. 2020;12(12). PubMed PMC

Sanz AB, Sanchez-Niño MD, Izquierdo MC, Gonzalez-Espinoza L, Ucero AC, Poveda J, et al. Macrophages and recently identified forms of cell death. Int Rev Immunol. 2014;33(1):9–22. 10.3109/08830185.2013.771183 PubMed DOI

Harijith A, Ebenezer DL, Natarajan V. Reactive oxygen species at the crossroads of inflammasome and inflammation. Front Physiol. 2014;5. PubMed PMC

Fernandes-Alnemri T, Wu J, Yu JW, Datta P, Miller B, Jankowski W, et al. The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation. Cell Death Differ 2007. 2007;14(9):9. PubMed PMC

Alnemri ES. Sensing cytoplasmic danger signals by the inflammasome. J Clin Immunol. 2010;30(4):512–9. 10.1007/s10875-010-9419-0 PubMed DOI PMC

Bergsbaken T, Fink SL, Cookson BT. Pyroptosis: host cell death and inflammation. Nat Rev Microbiol. 2009;7(2):99–109. 10.1038/nrmicro2070 PubMed DOI PMC

Duncan JA, Gao X, Huang MT-H, O’Connor BP, Thomas CE, Willingham SB et al. Neisseria gonorrhoeae activates the proteinase cathepsin B to mediate the signaling activities of the NLRP3 and ASC-containing inflammasome. Journal of immunology (Baltimore, Md: 1950). 2009;182(10):6460-9. PubMed PMC

Kayagaki N, Stowe IB, Lee BL, O’Rourke K, Anderson K, Warming S, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature. 2015;526(7575):666–71. 10.1038/nature15541 PubMed DOI

Mitchell PS, Sandstrom A, Vance RE. The NLRP1 inflammasome: new mechanistic insights and unresolved mysteries. Curr Opin Immunol. 2019;60:37–45. 10.1016/j.coi.2019.04.015 PubMed DOI PMC

Brydges SD, Broderick L, McGeough MD, Pena CA, Mueller JL, Hoffman HM. Divergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies. J Clin Invest. 2013;123(11):4695–705. 10.1172/JCI71543 PubMed DOI PMC

Papin S, Duquesnoy P, Cazeneuve C, Pantel J, Coppey-Moisan M, Dargemont C, et al. Alternative splicing at the MEFV locus involved in familial Mediterranean fever regulates translocation of the marenostrin/pyrin protein to the nucleus. Hum Mol Genet. 2000;9(20):3001–9. 10.1093/hmg/9.20.3001 PubMed DOI

Moghaddas F, Llamas R, De Nardo D, Martinez-Banaclocha H, Martinez-Garcia JJ, Mesa-Del-Castillo P, et al. A novel pyrin-Associated Autoinflammation with Neutrophilic Dermatosis mutation further defines 14-3-3 binding of pyrin and distinction to familial Mediterranean Fever. Ann Rheum Dis. 2017;76(12):2085–94. 10.1136/annrheumdis-2017-211473 PubMed DOI PMC

Demircan C, Akdogan N, Elmas L. Nicolau Syndrome secondary to Subcutaneous Glatiramer acetate injection. Int J Low Extrem Wounds. 2023;22(1):149–51. 10.1177/1534734620973144 PubMed DOI

Karki R, Sharma BR, Tuladhar S, Williams EP, Zalduondo L, Samir P, et al. Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and Mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell. 2021;184(1):149–e6817. 10.1016/j.cell.2020.11.025 PubMed DOI PMC

Yap JKY, Moriyama M, Iwasaki A. Inflammasomes and Pyroptosis as therapeutic targets for COVID-19. J Immunol. 2020;205(2):307–12. 10.4049/jimmunol.2000513 PubMed DOI PMC

Ratajczak MZ, Kucia M. SARS-CoV-2 infection and overactivation of Nlrp3 inflammasome as a trigger of cytokine storm and risk factor for damage of hematopoietic stem cells. Leukemia. 2020;34(7):1726–9. 10.1038/s41375-020-0887-9 PubMed DOI PMC

Yan Z, Qi W, Zhan J, Lin Z, Lin J, Xue X, et al. Activating Nrf2 signalling alleviates osteoarthritis development by inhibiting inflammasome activation. J Cell Mol Med. 2020;24(22):13046–57. 10.1111/jcmm.15905 PubMed DOI PMC

Wu Y, Zhang J, Yu S, Li Y, Zhu J, Zhang K, et al. Cell pyroptosis in health and inflammatory diseases. Cell Death Discovery. 2022;8(1):191. 10.1038/s41420-022-00998-3 PubMed DOI PMC

Wei X, Xie F, Zhou X, Wu Y, Yan H, Liu T, et al. Role of pyroptosis in inflammation and cancer. Cell Mol Immunol 2022. 2022;19(9):9. PubMed PMC

Chang SC, Yang WV. Hyperglycemia, tumorigenesis, and chronic inflammation. Crit Rev Oncol Hematol. 2016;108:146–53. 10.1016/j.critrevonc.2016.11.003 PubMed DOI

Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357(9255):539–45. 10.1016/S0140-6736(00)04046-0 PubMed DOI

Cowan AE, Moraru II, Schaff JC, Slepchenko BM, Loew LM. Chapter 8 - spatial modeling of Cell Signaling Networks. In: Asthagiri AR, Arkin AP, editors. Methods in Cell Biology. 2012;110:Academic, 195–221. PubMed PMC

Van Cleave C, Crans DC. The first-row transition metals in the periodic table of Medicine. Inorganics. 2019;7(9):111.10.3390/inorganics7090111 DOI

Chang CJ. Searching for harmony in transition-metal signaling. Nature Chemical Biology 2015 11:10. 2015;11(10):744-7. PubMed

Mendel RR, Smith AG, Marquet A, Warren MJ. Metal and cofactor insertion. Nat Prod Rep. 2007;24(5):963–71. 10.1039/b703112m PubMed DOI

Parigi G, Ravera E, Luchinat C. Paramagnetic effects in NMR for protein structures and ensembles: studies of metalloproteins. Curr Opin Struct Biol. 2022;74. PubMed

Baksh KA, Zamble DB. Allosteric control of metal-responsive transcriptional regulators in bacteria. J Biol Chem. 2020;295(6):1673–84. 10.1074/jbc.REV119.011444 PubMed DOI PMC

Yamasaki S, Sakata-Sogawa K, Hasegawa A, Suzuki T, Kabu K, Sato E, et al. Zinc is a novel intracellular second messenger. J Cell Biol. 2007;177(4):637–45. 10.1083/jcb.200702081 PubMed DOI PMC

Ackerman CM, Lee S, Chang CJ. Analytical Methods for Imaging Metals in Biology: from transition metal metabolism to Transition Metal Signaling. Anal Chem. 2017;89(1):22–41. 10.1021/acs.analchem.6b04631 PubMed DOI PMC

Holm RH, Kennepohl P, Solomon EI. Structural and functional aspects of Metal sites in Biology. Chem Rev. 1996;96(7):2239–314. 10.1021/cr9500390 PubMed DOI

Chiarelli R, Roccheri MC. Heavy Metals and Metalloids as Autophagy Inducing Agents: Focus on Cadmium and Arsenic. Cells 2012, Vol 1, Pages 597–616. 2012;1(3):597–616. PubMed PMC

Crichton R. Iron Metabolism: From Molecular Mechanisms to Clinical Consequences: 3rd Edition. Iron Metabolism: From Molecular Mechanisms to Clinical Consequences: 3rd Edition. 2009:1-461.

Dutt S, Hamza I, Bartnikas TB. Molecular mechanisms of Iron and Heme Metabolism. Annu Rev Nutr. 2022;42:311–35. 10.1146/annurev-nutr-062320-112625 PubMed DOI PMC

Zhang M, Liu Z, Le Y, Gu Z, Zhao H. Iron-Sulfur Clusters: A Key Factor of Regulated Cell Death in Cancer. Oxidative medicine and cellular longevity. 2022;2022. PubMed PMC

Hurrell R, Egli I. Iron bioavailability and dietary reference values. Am J Clin Nutr. 2010;91(5). PubMed

Bruzzese A, Martino EA, Mendicino F, Lucia E, Olivito V, Bova C et al. Iron chelation therapy. Eur J Haematol. 2023;110(5). PubMed

Hatcher HC, Singh RN, Torti FM, Torti SV. Synthetic and natural iron chelators: therapeutic potential and clinical use. Future Med Chem. 2009;1(9):1643–70. 10.4155/fmc.09.121 PubMed DOI PMC

Krzywoszyńska K, Witkowska D, Swiatek-kozlowska J, Szebesczyk A, Kozłowski H. General aspects of metal ions as signaling agents in health and disease. Biomolecules. 2020;10(10):1–30.10.3390/biom10101417 PubMed DOI PMC

Duck KA, Connor JR. Iron uptake and transport across physiological barriers. Biometals. 2016;29(4):573. 10.1007/s10534-016-9952-2 PubMed DOI PMC

West AR, Oates PS. Mechanisms of heme iron absorption: current questions and controversies. World J Gastroenterology: WJG. 2008;14(26):4101.10.3748/wjg.14.4101 PubMed DOI PMC

White C, Yuan X, Schmidt PJ, Bresciani E, Samuel TK, Campagna D, et al. HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. Cell Metabol. 2013;17(2):261.10.1016/j.cmet.2013.01.005 PubMed DOI PMC

Rajagopal A, Rao AU, Amigo J, Tian M, Upadhyay SK, Hall C, et al. Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins. Nature. 2008;453(7198):1127. 10.1038/nature06934 PubMed DOI PMC

Uzel C. MEC. Absorption of heme iron. PubMed

Mackenzie B, Garrick MD. Iron imports. II. Iron uptake at the apical membrane in the intestine. Am J Physiol Gastrointest Liver Physiol. 2005;289(6). PubMed

Andrews NC. Forging a field: the golden age of iron biology. Blood. 2008;112(2):219. 10.1182/blood-2007-12-077388 PubMed DOI PMC

Zhang N, Yu X, Xie J, Xu H. New insights into the role of Ferritin in Iron Homeostasis and neurodegenerative diseases. Mol Neurobiol. 2021;58(6):2812–23. 10.1007/s12035-020-02277-7 PubMed DOI

Ganz T. Cellular iron: ferroportin is the only way out. Cell Metabol. 2005;1(3):155–7.10.1016/j.cmet.2005.02.005 PubMed DOI

Vulpe CD, Kuo YM, Murphy TL, Cowley L, Askwith C, Libina N, et al. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet. 1999;21(2):195–9. 10.1038/5979 PubMed DOI

Gomme PT, McCann KB. Transferrin: structure, function and potential therapeutic actions. Drug Discovery Today. 2005;10(4):267–73. 10.1016/S1359-6446(04)03333-1 PubMed DOI

Abbaspour N, Hurrell R, Kelishadi R. Review on iron and its importance for human health. J Res Med Sciences: Official J Isfahan Univ Med Sci. 2014;19(2):164. PubMed PMC

Haber F, Weiss J, Seph JO, Eiss W. The Catalytic Decom position o f hydrogen peroxide by Iron Salts* by F r it z H aber and.

Barbehenn R, Dodick T, Poopat U, Spencer B. Fenton-type reactions and iron concentrations in the midgut fluids of tree-feeding caterpillars. Arch Insect Biochem Physiol. 2005;60(1):32–43. 10.1002/arch.20079 PubMed DOI

Sukhbaatar N, Weichhart T. Iron Regulation: macrophages in control. Pharmaceuticals. 2018;11(4). PubMed PMC

Yang WS, Sriramaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell. 2014;156(1–2):317–31. 10.1016/j.cell.2013.12.010 PubMed DOI PMC

Lei P, Bai T, Sun Y. Mechanisms of ferroptosis and relations with regulated cell death: a review. Front Physiol. 2019;10(FEB):139. 10.3389/fphys.2019.00139 PubMed DOI PMC

Bouchaoui H, Mahoney-Sanchez L, Garçon G, Berdeaux O, Alleman LY, Devos D, et al. ACSL4 and the lipoxygenases 15/15B are pivotal for ferroptosis induced by iron and PUFA dyshomeostasis in dopaminergic neurons. Free Radic Biol Med. 2023;195:145–57. 10.1016/j.freeradbiomed.2022.12.086 PubMed DOI

Hider R, Aviles MV, Chen YL, Latunde-Dada GO. The role of GSH in Intracellular Iron trafficking. Int J Mol Sci. 2021;22(3):1–13.10.3390/ijms22031278 PubMed DOI PMC

Hambright WS, Fonseca RS, Chen L, Na R, Ran Q. Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration. Redox Biol. 2017;12:8–17. 10.1016/j.redox.2017.01.021 PubMed DOI PMC

Ayton S, Faux NG, Bush AI, Weiner MW, Aisen P, Petersen R et al. Ferritin levels in the cerebrospinal fluid predict Alzheimer’s disease outcomes and are regulated by APOE. Nat Commun. 2015;6. PubMed PMC

Ashraf A, Jeandriens J, Parkes HG, So PW. Iron dyshomeostasis, lipid peroxidation and perturbed expression of cystine/glutamate antiporter in Alzheimer’s disease: Evidence of ferroptosis. Redox Biol. 2020;32. PubMed PMC

Wu A, Feng B, Yu J, Yan L, Che L, Zhuo Y et al. Fibroblast growth factor 21 attenuates iron overload-induced liver injury and fibrosis by inhibiting ferroptosis. Redox Biol. 2021;46. PubMed PMC

Adedoyin O, Boddu R, Traylor A, Lever JM, Bolisetty S, George JF, et al. Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells. Am J Physiol Ren Physiol. 2018;314(5):F702–14.10.1152/ajprenal.00044.2017 PubMed DOI PMC

Menon AV, Liu J, Tsai HP, Zeng L, Yang S, Asnani A, et al. Excess heme upregulates heme oxygenase 1 and promotes cardiac ferroptosis in mice with sickle cell disease. Blood. 2022;139(6):936–41. 10.1182/blood.2020008455 PubMed DOI PMC

Ma C, Wu X, Zhang X, Liu X, Deng G. Heme oxygenase-1 modulates ferroptosis by fine-tuning levels of intracellular iron and reactive oxygen species of macrophages in response to Bacillus Calmette-Guerin infection. Front Cell Infect Microbiol. 2022;12. PubMed PMC

Zhang P, Chen L, Zhao Q, Du X, Bi M, Li Y, et al. Ferroptosis was more initial in cell death caused by iron overload and its underlying mechanism in Parkinson’s disease. Free Radic Biol Med. 2020;152:227–34. 10.1016/j.freeradbiomed.2020.03.015 PubMed DOI

Liu Y, Gu W. p53 in ferroptosis regulation: the new weapon for the old guardian. Cell Death Differ. 2022;29(5):895–910. 10.1038/s41418-022-00943-y PubMed DOI PMC

Mancias JD, Wang X, Gygi SP, Harper JW, Kimmelman AC. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nat 2014. 2014;509(7498):7498. PubMed PMC

Kaur J, Debnath J. Autophagy at the crossroads of catabolism and anabolism. Nat Reviews Mol Cell Biology 2015. 2015;16(8):8. PubMed

Gao M, Monian P, Pan Q, Zhang W, Xiang J, Jiang X. Ferroptosis is an autophagic cell death process. Cell Res. 2016;26(9):1021. 10.1038/cr.2016.95 PubMed DOI PMC

Gryzik M, Asperti M, Denardo A, Arosio P, Poli M. NCOA4-mediated ferritinophagy promotes ferroptosis induced by erastin, but not by RSL3 in HeLa cells. Biochim et Biophys acta Mol cell Res. 2021;1868(2). PubMed

Hou W, Xie Y, Song X, Sun X, Lotze MT, Zeh HJ, et al. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy. 2016;12(8):1425–8. 10.1080/15548627.2016.1187366 PubMed DOI PMC

Bellelli R, Federico G, Matte A, Colecchia D, Iolascon A, Chiariello M, et al. NCOA4 Deficiency impairs systemic Iron homeostasis. Cell Rep. 2016;14(3):411–21. 10.1016/j.celrep.2015.12.065 PubMed DOI

Sun K, Li C, Liao S, Yao X, Ouyang Y, Liu Y, et al. Ferritinophagy, a form of autophagic ferroptosis: new insights into cancer treatment. Front Pharmacol. 2022;13:4548.10.3389/fphar.2022.1043344 PubMed DOI PMC

Tang YS, Zhao YH, Zhong Y, Li XZ, Pu JX, Luo YC, et al. Neferine inhibits LPS-ATP-induced endothelial cell pyroptosis via regulation of ROS/NLRP3/Caspase-1 signaling pathway. Inflamm Research: Official J Eur Histamine Res Soc [et al]. 2019;68(9):727–38.10.1007/s00011-019-01256-6 PubMed DOI

Jomova K, Makova M, Alomar SY, Alwasel SH, Nepovimova E, Kuca K et al. Essential metals in health and disease. Chemico-Biol Interact. 2022;367. PubMed

Hübner C, Haase H. Interactions of zinc- and redox-signaling pathways. Redox Biol. 2021;41. PubMed PMC

Kimura T, Kambe T. The functions of Metallothionein and ZIP and ZnT transporters: an overview and perspective. Int J Mol Sci. 2016;17(3). PubMed PMC

Bin BH, Seo J, Kim ST, Function. Structure, and Transport Aspects of ZIP and ZnT Zinc Transporters in Immune Cells. Journal of Immunology Research. 2018;2018. PubMed PMC

Maret W. The redox biology of redox-inert zinc ions. Free Radic Biol Med. 2019;134:311–26. 10.1016/j.freeradbiomed.2019.01.006 PubMed DOI

Kręzel A, Maret W. Dual nanomolar and picomolar zn(II) binding properties of metallothionein. J Am Chem Soc. 2007;129(35):10911–21. 10.1021/ja071979s PubMed DOI

Krężel A, Maret W. The functions of metamorphic metallothioneins in zinc and copper metabolism. Int J Mol Sci. 2017;18(6). PubMed PMC

Thornalley PJ, Vašák M. Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals. Biochim Biophys Acta. 1985;827(1):36–44. 10.1016/0167-4838(85)90098-6 PubMed DOI

Tapiero H, Tew KD. Trace elements in human physiology and pathology: zinc and metallothioneins. Biomed Pharmacotherapy. 2003;57(9):399–411.10.1016/S0753-3322(03)00081-7 PubMed DOI

Maret W. Zinc coordination environments in proteins as redox sensors and signal transducers. Antioxid Redox Signal. 2006;8(9–10):1419–41. 10.1089/ars.2006.8.1419 PubMed DOI

Jacob C, Maret W, Vallee BL. Control of zinc transfer between thionein, metallothionein, and zinc proteins. Proc Natl Acad Sci USA. 1998;95(7):3489–94. 10.1073/pnas.95.7.3489 PubMed DOI PMC

Jiang LJ, Maret W, Vallee BL. The glutathione redox couple modulates zinc transfer from metallothionein to zinc-depleted sorbitol dehydrogenase. Proc Natl Acad Sci USA. 1998;95(7):3483–8. 10.1073/pnas.95.7.3483 PubMed DOI PMC

Maret W, Vallee BL. Thiolate ligands in metallothionein confer redox activity on zinc clusters. Proc Natl Acad Sci USA. 1998;95(7):3478–82. 10.1073/pnas.95.7.3478 PubMed DOI PMC

Samman S. Dietary versus cellular zinc: the antioxidant paradox. Free Radic Biol Med. 1993;14(1):95–6. 10.1016/0891-5849(93)90514-U PubMed DOI

Schrauzer GN. Anticarcinogenic effects of selenium. Cell Mol Life Sci. 2000;57(13–14):1864–73. 10.1007/PL00000668 PubMed DOI PMC

Schrauzer GN. Antioxidant supplementation increases skin cancer risk, or, why zinc should not be considered an antioxidant. J Nutr. 2008;138(4):820. 10.1093/jn/138.4.820 PubMed DOI

Chen PH, Wu J, Xu Y, Ding CKC, Mestre AA, Lin CC et al. Zinc transporter ZIP7 is a novel determinant of ferroptosis. Cell Death Dis. 2021;12(2). PubMed PMC

Ge Mh, Tian H, Mao L, Li D, Jq L, Hs H, et al. Zinc attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury by activating Nrf2/GPX4 defense pathway. CNS Neurosci Ther. 2021;27(9):1023–40. 10.1111/cns.13657 PubMed DOI PMC

Ferrer X, Moreno JJ. Effects of copper, iron and zinc on oedema formation induced by phospholipase A2. Comparative biochemistry and physiology C. Comp Pharmacol Toxicol. 1992;102(2):325–7. PubMed

Zhang Y, Aizenman E, DeFranco DB, Rosenberg PA. Intracellular zinc release, 12-lipoxygenase activation and MAPK dependent neuronal and oligodendroglial death. Mol Med. 2007;13(7–8):350–5. 10.2119/2007-00042.Zhang PubMed DOI PMC

Morita Y, Sawada M, Seno H, Takaishi S, Fukuzawa H, Miyake N, et al. Identification of xanthine dehydrogenase/xanthine oxidase as a rat paneth cell zinc-binding protein. Biochimica et Biophysica Acta (BBA) -. Mol Cell Res. 2001;1540(1):43–9. PubMed

Wang Z, Li X, Du S, Sun X, Huang J, Shao Y. Protective effects of Zinc on Salmonella Invasion, intestinal morphology and Immune Response of Young pigeons infected with Salmonella enterica Serovar Typhimurium. Biol Trace Elem Res. 2022;200(11):4817–27. 10.1007/s12011-021-03057-7 PubMed DOI

Zhao Z, Hu X, Wang J, Wang J, Hou Y, Chen S. Zinc finger E-Box binding homeobox 2 (ZEB2)-induced astrogliosis protected neuron from pyroptosis in cerebral ischemia and reperfusion injury. Bioengineered. 2021;12(2):12917–30. 10.1080/21655979.2021.2012551 PubMed DOI PMC

Mehdi Y, Hornick JL, Istasse L, Dufrasne I. Selenium in the environment, metabolism and involvement in body functions. Molecules. 2013;18(3):3292–311. 10.3390/molecules18033292 PubMed DOI PMC

Ingold I, Berndt C, Schmitt S, Doll S, Poschmann G, Buday K, et al. Selenium utilization by GPX4 is required to Prevent Hydroperoxide-Induced ferroptosis. Cell. 2018;172(3):409–e2221. 10.1016/j.cell.2017.11.048 PubMed DOI

Yin K, Sun X, Zheng Y, Zhang W, Lin H. Bisphenol A exacerbates selenium deficiency-induced pyroptosis via the NF-κB/NLRP3/Caspase-1 pathway in chicken trachea. Comp Biochem Physiol C: Toxicol Pharmacol. 2023;263:109488. PubMed

Conrad M, Proneth B. Selenium: tracing another essential element of ferroptotic cell death. Cell Chem Biology. 2020;27(4):409–19.10.1016/j.chembiol.2020.03.012 PubMed DOI

Hatfield DL, Gladyshev VN. How selenium has altered our understanding of the genetic code. Mol Cell Biol. 2002;22(11):3565–76. 10.1128/MCB.22.11.3565-3576.2002 PubMed DOI PMC

Stoytcheva ZR, Berry MJ. Transcriptional regulation of mammalian selenoprotein expression. Biochim Biophys Acta. 2009;1790(11):1429–40. 10.1016/j.bbagen.2009.05.012 PubMed DOI PMC

Alim I, Caulfield JT, Chen Y, Swarup V, Geschwind DH, Ivanova E, et al. Selenium drives a Transcriptional Adaptive Program to Block Ferroptosis and treat stroke. Cell. 2019;177(5):1262–e7925. 10.1016/j.cell.2019.03.032 PubMed DOI

Yao Y, Chen Z, Zhang H, Chen C, Zeng M, Yunis J, et al. Selenium-GPX4 axis protects follicular helper T cells from ferroptosis. Nat Immunol. 2021;22(9):1127–39. 10.1038/s41590-021-00996-0 PubMed DOI

Fradejas N, Carlson BA, Rijntjes E, Becker NP, Tobe R, Schweizer U. Mammalian Trit1 is a tRNA([Ser]Sec)-isopentenyl transferase required for full selenoprotein expression. Biochem J. 2013;450(2):427–32. 10.1042/BJ20121713 PubMed DOI

Zhang X, Guo Y, Li H, Han L. FIN56, a novel ferroptosis inducer, triggers lysosomal membrane permeabilization in a TFEB-dependent manner in glioblastoma. J Cancer. 2021;12(22):6610. 10.7150/jca.58500 PubMed DOI PMC

Ryu H, Lee J, Zaman K, Kubilis J, Ferrante RJ, Ross BD, et al. Sp1 and Sp3 are oxidative Stress-Inducible, Antideath Transcription Factors in cortical neurons. J Neurosci. 2003;23(9):3597. 10.1523/JNEUROSCI.23-09-03597.2003 PubMed DOI PMC

Müller A, Cadenas E, Graf P, Sies H. A novel biologically active seleno-organic compound–I. glutathione peroxidase-like activity in vitro and antioxidant capacity of PZ 51 (Ebselen). Biochem Pharmacol. 1984;33(20):3235–9. 10.1016/0006-2952(84)90083-2 PubMed DOI

Wu H, Luan Y, Wang H, Zhang P, Liu S, Wang P, et al. Selenium inhibits ferroptosis and ameliorates autistic-like behaviors of BTBR mice by regulating the Nrf2/GPx4 pathway. Brain Res Bull. 2022;183:38–48. 10.1016/j.brainresbull.2022.02.018 PubMed DOI

Tuo QZ, Masaldan S, Southon A, Mawal C, Ayton S, Bush AI, et al. Characterization of Selenium compounds for anti-ferroptotic activity in neuronal cells and after cerebral ischemia-reperfusion Injury. Neurotherapeutics: J Am Soc Experimental Neurother. 2021;18(4):2682–91.10.1007/s13311-021-01111-9 PubMed DOI PMC

Wang L, Yang F, Hu M, Chen G, Wang Y, Xu H et al. GPX4 utilization by selenium is required to alleviate cadmium-induced ferroptosis and pyroptosis in sheep kidney. Environ Toxicol. 2023. PubMed

Feng J, Yang F, Wu H, Xing C, Xue H, Zhang L, et al. Selenium protects against cadmium-induced cardiac injury by attenuating programmed cell death via PI3K/AKT/PTEN signaling. Environ Toxicol. 2022;37(5):1185–97. 10.1002/tox.23475 PubMed DOI

Liu S, Chen Q, Yan L, Ren Y, Fan J, Zhang X et al. Phytosomal tripterine with selenium modification attenuates the cytotoxicity and restrains the inflammatory evolution via inhibiting NLRP3 inflammasome activation and pyroptosis. Int Immunopharmacol. 2022;108. PubMed

Mahan DC, Cline TR, Richert B. Effects of dietary levels of selenium-enriched yeast and sodium selenite as selenium sources fed to growing-finishing pigs on performance, tissue selenium, serum glutathione peroxidase activity, carcass characteristics, and loin quality. J Anim Sci. 1999;77(8):2172–9. 10.2527/1999.7782172x PubMed DOI

Pengcheng X, Xu S, Wei C, Xiaodan H. Yeast selenium exerts an antioxidant effect by regulating the Level of Selenoprotein to Antagonize Cd-Induced pyroptosis of Chicken Liver. Biol Trace Elem Res. 2022;200(9):4079–88. 10.1007/s12011-021-02984-9 PubMed DOI

Song L, Jiang Z, Zhang X, Song Y, Xing Y, Wang G. Selenium Deficiency via the ROS/NLRP3/IL-1β signaling pathway leads to Pyroptosis Injury in Pig Spleen. Biological Trace Element Research; 2023. PubMed

Liu Q, Du P, Zhu Y, Zhang X, Cai J, Zhang Z. Thioredoxin reductase 3 suppression promotes colitis and carcinogenesis via activating pyroptosis and necrosis. Cell Mol Life Sci. 2022;79(2). PubMed PMC

Aliaga ME, López-Alarcón C, Bridi R, Speisky H. Redox-implications associated with the formation of complexes between copper ions and reduced or oxidized glutathione. J Inorg Biochem. 2016;154:78–88. 10.1016/j.jinorgbio.2015.08.005 PubMed DOI

Kozlowski H, Kolkowska P, Watly J, Krzywoszynska K, Potocki S. General aspects of metal toxicity. Curr Med Chem. 2014;21(33):3721–40. 10.2174/0929867321666140716093838 PubMed DOI

Maryon EB, Molloy SA, Ivy K, Yu H, Kaplan JH. Rate and regulation of copper transport by human copper transporter 1 (hCTR1). J Biol Chem. 2013;288(25):18035–46. 10.1074/jbc.M112.442426 PubMed DOI PMC

Scheiber IF, Mercer JFB, Dringen R. Copper accumulation by cultured astrocytes. Neurochem Int. 2010;56(3):451–60. 10.1016/j.neuint.2009.12.002 PubMed DOI

Chen L, Min J, Wang F. Copper homeostasis and cuproptosis in health and disease. Signal Transduct Target Therapy. 2022;7(1). PubMed PMC

Luza SC, Speisky HC. Liver copper storage and transport during development: implications for cytotoxicity. Am J Clin Nutr. 1996;63(5). PubMed

Arredondo M, Núñez MT. Iron and copper metabolism. Mol Aspects Med. 2005;26(4–5):313–27. 10.1016/j.mam.2005.07.010 PubMed DOI

Jeong SY, David S. Glycosylphosphatidylinositol-anchored ceruloplasmin is required for iron efflux from cells in the central nervous system. J Biol Chem. 2003;278(29):27144–8. 10.1074/jbc.M301988200 PubMed DOI

Bento I, Peixoto C, Zaitsev VN, Lindley PF. Ceruloplasmin revisited: structural and functional roles of various metal cation-binding sites. Acta Crystallogr Sect D Biol Crystallogr. 2007;63(Pt 2):240–8. 10.1107/S090744490604947X PubMed DOI PMC

Xue Q, Yan D, Chen X, Li X, Kang R, Klionsky DJ et al. Copper-dependent autophagic degradation of GPX4 drives ferroptosis. Autophagy. 2023. PubMed PMC

Li F, Wu X, Liu H, Liu M, Yue Z, Wu Z et al. Copper depletion strongly enhances ferroptosis via mitochondrial perturbation and reduction in antioxidative mechanisms. Antioxid (Basel Switzerland). 2022;11(11). PubMed PMC

Jhelum P, Santos-Nogueira E, Teo W, Haumont A, Lenoël I, Stys PK, et al. Ferroptosis mediates Cuprizone-Induced loss of oligodendrocytes and demyelination. J Neuroscience: Official J Soc Neurosci. 2020;40(48):9327–41.10.1523/JNEUROSCI.1749-20.2020 PubMed DOI PMC

Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Sci (New York NY). 2022;375(6586):1254–61.10.1126/science.abf0529 PubMed DOI PMC

Xu Y, Yang W, Han Y, Bian K, Zeng W, Hao L et al. Biomimetic Molybdenum Sulfide-Catalyzed Tumor Ferroptosis and Bioimaging. Small (Weinheim an der Bergstrasse, Germany). 2023:2207544. PubMed

Novotny JA, Peterson CA. Molybdenum. Advances in nutrition (Bethesda. Md). 2018;9(3):272–3. PubMed PMC

Gu X, Ali T, Chen R, Hu G, Zhuang Y, Luo J et al. In Vivo Studies of Molybdenum-Induced Apoptosis in Kidney Cells of Caprine. Biological Trace Element Research 2015 165:1. 2015;165(1):51 – 8. PubMed

Burguera JL, Burguera M. Molybdenum in human whole blood of adult residents of the Merida State (Venezuela). J Trace Elem Med Biol. 2007;21(3):178–83. 10.1016/j.jtemb.2007.03.005 PubMed DOI

Hu Z, Nie G, Luo J, Hu R, Li G, Hu G, et al. Molybdenum and cadmium co-induce pyroptosis via inhibiting Nrf2-Mediated antioxidant defense response in the brain of ducks. Biol Trace Elem Res. 2023;201(2):874–87. 10.1007/s12011-022-03170-1 PubMed DOI

Cao P, Nie G, Luo J, Hu R, Li G, Hu G, et al. Cadmium and molybdenum co-induce pyroptosis and apoptosis via the PTEN/PI3K/AKT axis in the livers of Shaoxing ducks (Anas platyrhynchos). Food Function. 2022;13(4):2142–54. 10.1039/D1FO02855C PubMed DOI

Zhuang J, Nie G, Hu R, Wang C, Xing C, Li G et al. Inhibition of autophagy aggravates molybdenum-induced mitochondrial dysfunction by aggravating oxidative stress in duck renal tubular epithelial cells. Ecotoxicol Environ Saf. 2021;209. PubMed

Leyssens L, Vinck B, Van Der Straeten C, Wuyts F, Maes L. Cobalt toxicity in humans-A review of the potential sources and systemic health effects. Toxicology. 2017;387:43–56. 10.1016/j.tox.2017.05.015 PubMed DOI

Liu Y, Zhu W, Ni D, Zhou Z, Gu JH, Zhang W et al. Alpha lipoic acid antagonizes cytotoxicity of cobalt nanoparticles by inhibiting ferroptosis-like cell death. J Nanobiotechnol. 2020;18(1). PubMed PMC

Leonard S, Gannett PM, Rojanasakul Y, Schwegler-Berry D, Castranova V, Vallyathan V, et al. Cobalt-mediated generation of reactive oxygen species and its possible mechanism. J Inorg Biochem. 1998;70(3–4):239–44. 10.1016/S0162-0134(98)10022-3 PubMed DOI

Xue S, Xu Y, Xu S, Zhong Y, Ruan G, Ma J, et al. Mitophagy impairment mediates the pathogenesis of CoCrMo particle-induced osteolysis via NLRP3/caspase-1/GSDMD-dependent pyroptosis in macrophages. Chem Eng J. 2022;435:135115.10.1016/j.cej.2022.135115 DOI

Liu W, Gan Y, Ding Y, Zhang L, Jiao X, Liu L et al. Autophagy promotes GSDME-mediated pyroptosis via intrinsic and extrinsic apoptotic pathways in cobalt chloride-induced hypoxia reoxygenation-acute kidney injury. Ecotoxicol Environ Saf. 2022;242. PubMed

Begum W, Rai S, Banerjee S, Bhattacharjee S, Mondal MH, Bhattarai A, et al. A comprehensive review on the sources, essentiality and toxicological profile of nickel. RSC Adv. 2022;12(15):9139–53. 10.1039/D2RA00378C PubMed DOI PMC

Zambelli B, Ciurli S. Nickel and human health. Metal Ions Life Sci. 2013;13:321–57.10.1007/978-94-007-7500-8_10 PubMed DOI

Barceloux DG, Nickel. J Toxicol Clin Toxicol. 1999;37(2):239–58. 10.1081/CLT-100102423 PubMed DOI

Wei L, Zuo Z, Yang Z, Yin H, Yang Y, Fang J et al. Mitochondria damage and ferroptosis involved in Ni-induced hepatotoxicity in mice. Toxicology. 2022;466. PubMed

Chen P, Wang RR, Ma XJ, Liu Q, Ni JZ. Different forms of selenoprotein M differentially affect Aβ aggregation and ROS generation. Int J Mol Sci 2013. 2013;14(3):4385–99.10.3390/ijms14034385 PubMed DOI PMC

Ma W, Liu Y, Xu L, Gai X, Sun Y, Qiao S, et al. The role of selenoprotein M in nickel-induced pyroptosis in mice spleen tissue via oxidative stress. Environ Sci Pollut Res Int. 2023;30(12):34270–81. 10.1007/s11356-022-24597-y PubMed DOI

Douple EB, Richmond RC. A review of platinum complex biochemistry suggests a rationale for combined platinum-radiotherapy. Int J Radiation Oncology*Biology*Physics. 1979;5(8):1335–9.10.1016/0360-3016(79)90665-5 PubMed DOI

Rinkovec J. Platinum, palladium, and rhodium in airborne particulate matter. Arh Hig Rada Toksikol. 2019;70(4):224–31. 10.2478/aiht-2019-70-3293 PubMed DOI

Guo J, Xu B, Han Q, Zhou H, Xia Y, Gong C, et al. Ferroptosis: a Novel Anti-tumor Action for Cisplatin. Cancer Res Treatment: Official J Korean Cancer Association. 2018;50(2):445.10.4143/crt.2016.572 PubMed DOI PMC

Ikeda Y, Hamano H, Horinouchi Y, Miyamoto L, Hirayama T, Nagasawa H, et al. Role of ferroptosis in cisplatin-induced acute nephrotoxicity in mice. J Trace Elem Med Biol. 2021;67:126798. 10.1016/j.jtemb.2021.126798 PubMed DOI

Li Y, Li K, Zhao W, Wang H, Xue X, Chen X et al. VPA improves ferroptosis in tubular epithelial cells after cisplatin-induced acute kidney injury. Front Pharmacol. 2023;14. PubMed PMC

Li L, Qiu C, Hou M, Wang X, Huang C, Zou J, et al. Ferroptosis in ovarian cancer: a novel therapeutic strategy. Front Oncol. 2021;11:665945. 10.3389/fonc.2021.665945 PubMed DOI PMC

Hu Z, Zhang H, Yi B, Yang S, Liu J, Hu J et al. VDR activation attenuate cisplatin induced AKI by inhibiting ferroptosis. Cell Death & Disease 2020 11:1. 2020;11(1):1–11. PubMed PMC

Fuertes M, Castilla J, Alonso C, Pérez J. Cisplatin biochemical mechanism of action: from cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways. Curr Med Chem. 2003;10(3):257–66. 10.2174/0929867033368484 PubMed DOI

Li L, Shang J, Zhang Y, Liu S, Peng Y, Zhou Z, et al. MEG3 is a prognostic factor for CRC and promotes chemosensitivity by enhancing oxaliplatin-induced cell apoptosis. Oncol Rep. 2017;38(3):1383–92. 10.3892/or.2017.5828 PubMed DOI PMC

Wang G, Wang J-J, Zhi-Min Z, Xu X-N, Shi F, Fu X-L. Targeting critical pathways in ferroptosis and enhancing antitumor therapy of platinum drugs for colorectal cancer. Sci Prog. 2023;106(1):00368504221147173. 10.1177/00368504221147173 PubMed DOI PMC

Yang C, Zhang Y, Lin S, Liu Y, Li W. Suppressing the KIF20A/NUAK1/Nrf2/GPX4 signaling pathway induces ferroptosis and enhances the sensitivity of colorectal cancer to oxaliplatin. Aging. 2021;13(10):13515–34. 10.18632/aging.202774 PubMed DOI PMC

Liu Z, Cai J, Jiang G, Wang M, Wu C, Su K, et al. Novel platinum(IV) complexes intervene oxaliplatin resistance in colon cancer via inducing ferroptosis and apoptosis. Eur J Med Chem. 2024;263:115968. 10.1016/j.ejmech.2023.115968 PubMed DOI

Qi D, Xing L, Shen L, Sun W, Cai C, Xue C, et al. A GSH-depleted platinum(IV) prodrug triggers ferroptotic cell death in breast cancer. Chin Chem Lett. 2022;33(10):4595–9.10.1016/j.cclet.2022.03.105 DOI

Huang ZX, Zhang QY, Wang Y, Chen R, Wang YQ, Huang ZS et al. Inhibition of caspase-3-mediated GSDME-derived pyroptosis aids in noncancerous tissue protection of squamous cell carcinoma patients during cisplatin-based chemotherapy. Am J CANCER Res. 2020;10(12). PubMed PMC

Ling YY, Xia XY, Hao L, Wang WJ, Zhang H, Liu LY, et al. Simultaneous photoactivation of cGAS-STING pathway and pyroptosis by platinum (II) triphenylamine complexes for Cancer Immunotherapy. Angewandte Chemie - Int Ed. 2022;61:43.10.1002/anie.202210988 PubMed DOI

Rahimzadeh MR, Rahimzadeh MR, Kazemi S, Moghadamnia AA. Cadmium toxicity and treatment: an update. Caspian J Intern Med. 2017;8(3):135. PubMed PMC

Genchi G, Sinicropi MS, Lauria G, Carocci A, Catalano A. The effects of Cadmium Toxicity. Int J Environ Res Public Health. 2020;17(11). PubMed PMC

Zhang Y, Guo S, Wang S, Li X, Hou D, Li H et al. LncRNA OIP5-AS1 inhibits ferroptosis in prostate cancer with long-term cadmium exposure through miR-128-3p/SLC7A11 signaling. Ecotoxicol Environ Saf. 2021;220. PubMed

Marisa D, Aflanie I, Muthmainah N, Suhartono E. Interaction of cadmium-cysteine binding and oxidation of protein causes of blood thrombosis. Journal of Physics: Conference Series. 2019;1374(1):012034-.

Zeng L, Zhou J, Wang X, Zhang Y, Wang M, Su P. Cadmium attenuates testosterone synthesis by promoting ferroptosis and blocking autophagosome-lysosome fusion. Free Radic Biol Med. 2021;176:176–88. 10.1016/j.freeradbiomed.2021.09.028 PubMed DOI

He Z, Shen P, Feng L, Hao H, He Y, Fan G et al. Cadmium induces liver dysfunction and ferroptosis through the endoplasmic stress-ferritinophagy axis. Ecotoxicol Environ Saf. 2022;245. PubMed

Wang YJ, Yan J, Yin F, Li L, Qin YG, Meng CY, et al. Role of autophagy in cadmium-induced testicular injury. Hum Exp Toxicol. 2017;36(10):1039–48. 10.1177/0960327116678300 PubMed DOI

Wu X, Guo X, Wang H, Zhou S, Li L, Chen X et al. A brief exposure to cadmium impairs Leydig cell regeneration in the adult rat testis. Sci Rep. 2017;7(1). PubMed PMC

Cupertino MC, Novaes RD, Santos EC, Neves AC, Silva E, Oliveira JA et al. Differential Susceptibility of Germ and Leydig Cells to Cadmium-Mediated Toxicity: Impact on Testis Structure, Adiponectin Levels, and Steroidogenesis. Oxidative medicine and cellular longevity. 2017;2017. PubMed PMC

Ji YL, Wang H, Meng C, Zhao XF, Zhang C, Zhang Y, et al. Melatonin alleviates cadmium-induced cellular stress and germ cell apoptosis in testes. J Pineal Res. 2012;52(1):71–9. 10.1111/j.1600-079X.2011.00921.x PubMed DOI

Mathur PP, D’Cruz SC. The effect of environmental contaminants on testicular function. Asian J Androl. 2011;13(4):585. 10.1038/aja.2011.40 PubMed DOI PMC

Hu Y, Wu H, Lu C, Xu H, Li B, Guan W et al. Cadmium chloride exposure impairs the growth and behavior of Drosophila via ferroptosis. Sci Total Environ. 2023;865. PubMed

Chen PY, Ho YR, Wu MJ, Huang SP, Chen PK, Tai MH et al. Cytoprotective effects of fisetin against hypoxia-induced cell death in PC12 cells.6(1):287–96. PubMed

Hong H, Lin X, Xu Y, Tong T, Zhang J, He H et al. Cadmium induces ferroptosis mediated inflammation by activating Gpx4/Ager/p65 axis in pancreatic β-cells. Sci Total Environ. 2022;849. PubMed

Darwish WS, Chen Z, Li Y, Wu Y, Chiba H, Hui SP. Identification of cadmium-produced lipid hydroperoxides, transcriptomic changes in antioxidant enzymes, xenobiotic transporters, and pro-inflammatory markers in human breast cancer cells (MCF7) and protection with fat-soluble vitamins. Environ Sci Pollut Res. 2020;27(2):1978–90.10.1007/s11356-019-06834-z PubMed DOI

Wu H, Reizel T, Wang YJ, Lapiro JL, Kren BT, Schug J, et al. A negative reciprocal regulatory axis between cyclin D1 and HNF4α modulates cell cycle progression and metabolism in the liver. Proc Natl Acad Sci USA. 2020;117(29):17177–86. 10.1073/pnas.2002898117 PubMed DOI PMC

Zhang CY, Lin TJ, Nie GH, Hu RM, Pi SX, Wei ZJ et al. Cadmium and molybdenum co-induce pyroptosis via ROS/PTEN/PI3K/AKT axis in duck renal tubular epithelial cells. Environ Pollut. 2021;272. PubMed

Chou X, Ding F, Zhang X, Ding X, Gao H, Wu Q. Sirtuin-1 ameliorates cadmium-induced endoplasmic reticulum stress and pyroptosis through XBP-1s deacetylation in human renal tubular epithelial cells. Arch Toxicol. 2019;93(4):965–86. 10.1007/s00204-019-02415-8 PubMed DOI

Bernhoft RA. Mercury toxicity and treatment: a review of the literature. Journal of environmental and public health. 2012;2012. PubMed PMC

Chen J, Ma M, Wang R, Gao M, Hu L, Liu S et al. Roles of glutathione peroxidase 4 on the mercury-triggered ferroptosis in renal cells: implications for the antagonism between selenium and mercury. Metallomics: Integr Biometal Sci. 2023;15(3). PubMed

Ahn H, Kim J, Kang SG, Yoon Si, Ko HJ, Kim PH et al. Mercury and arsenic attenuate canonical and non-canonical NLRP3 inflammasome activation. Sci Rep. 2018;8(1). PubMed PMC

Gidlow DA. Lead toxicity. Occupational medicine (Oxford, England). 2015;65(5):348 – 56. PubMed

Shi F, Yang H, Sun G, Cui J, Li Z, Wang W, et al. Pb induces ferroptosis in choroid plexus epithelial cells via Fe metabolism. Neurotoxicology. 2023;95:107–16. 10.1016/j.neuro.2023.01.005 PubMed DOI

Su P, Wang D, Cao Z, Chen J, Zhang J. The role of NLRP3 in lead-induced neuroinflammation and possible underlying mechanism. Environ Pollut. 2021;287:117520. 10.1016/j.envpol.2021.117520 PubMed DOI

Bolt HM. The Janus face of uranium in toxicology. Arch Toxicol. 2022;96(3):689–90. 10.1007/s00204-022-03223-3 PubMed DOI PMC

Chen X, Wu G, Dang YX, Li Q, Xie MT, Li W, et al. Uranium triggers ferroptosis-like cell death in Vicia faba roots by increasing iron accumulation and inhibiting glutathione peroxidase activity. Environ Exp Bot. 2023;205:105122.10.1016/j.envexpbot.2022.105122 DOI

Yin J, Hu N, Yi L, Zhao W, Cheng X, Li G, et al. Identification of ferroptosis biomarker in AHH-1 lymphocytes Associated with Low Dose Radiation. Health Phys. 2021;120(5):541–51. 10.1097/HP.0000000000001385 PubMed DOI

Claro S, Oshiro MEM, Mortara RA, Paredes-Gamero EJ, Pereira GJS, Smaili SS, et al. γ-Rays-generated ROS induce apoptosis via mitochondrial and cell cycle alteration in smooth muscle cells. Int J Radiat Biol. 2014;90(10):914–27. 10.3109/09553002.2014.911988 PubMed DOI

Hao R, Ge J, Song X, Li F, Sun-Waterhouse D, Li D. Cadmium induces ferroptosis and apoptosis by modulating miR-34a-5p/Sirt1axis in PC12 cells. Environ Toxicol. 2022;37(1):41–51. 10.1002/tox.23376 PubMed DOI

Sun X, Ou Z, Xie M, Kang R, Fan Y, Niu X, et al. HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene. 2015;34(45):5617–25. 10.1038/onc.2015.32 PubMed DOI PMC