Heavy metals are naturally occurring components of the Earth's crust and persistent environmental pollutants. Human exposure to heavy metals occurs via various pathways, including inhalation of air/dust particles, ingesting contaminated water or soil, or through the food chain. Their bioaccumulation may lead to diverse toxic effects affecting different body tissues and organ systems. The toxicity of heavy metals depends on the properties of the given metal, dose, route, duration of exposure (acute or chronic), and extent of bioaccumulation. The detrimental impacts of heavy metals on human health are largely linked to their capacity to interfere with antioxidant defense mechanisms, primarily through their interaction with intracellular glutathione (GSH) or sulfhydryl groups (R-SH) of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and other enzyme systems. Although arsenic (As) is believed to bind directly to critical thiols, alternative hydrogen peroxide production processes have also been postulated. Heavy metals are known to interfere with signaling pathways and affect a variety of cellular processes, including cell growth, proliferation, survival, metabolism, and apoptosis. For example, cadmium can affect the BLC-2 family of proteins involved in mitochondrial death via the overexpression of antiapoptotic Bcl-2 and the suppression of proapoptotic (BAX, BAK) mechanisms, thus increasing the resistance of various cells to undergo malignant transformation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of antioxidant enzymes, the level of oxidative stress, and cellular resistance to oxidants and has been shown to act as a double-edged sword in response to arsenic-induced oxidative stress. Another mechanism of significant health threats and heavy metal (e.g., Pb) toxicity involves the substitution of essential metals (e.g., calcium (Ca), copper (Cu), and iron (Fe)) with structurally similar heavy metals (e.g., cadmium (Cd) and lead (Pb)) in the metal-binding sites of proteins. Displaced essential redox metals (copper, iron, manganese) from their natural metal-binding sites can catalyze the decomposition of hydrogen peroxide via the Fenton reaction and generate damaging ROS such as hydroxyl radicals, causing damage to lipids, proteins, and DNA. Conversely, some heavy metals, such as cadmium, can suppress the synthesis of nitric oxide radical (NO·), manifested by altered vasorelaxation and, consequently, blood pressure regulation. Pb-induced oxidative stress has been shown to be indirectly responsible for the depletion of nitric oxide due to its interaction with superoxide radical (O2·-), resulting in the formation of a potent biological oxidant, peroxynitrite (ONOO-). This review comprehensively discusses the mechanisms of heavy metal toxicity and their health effects. Aluminum (Al), cadmium (Cd), arsenic (As), mercury (Hg), lead (Pb), and chromium (Cr) and their roles in the development of gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer's and Parkinson's diseases), cardiovascular, and cancer (e.g. renal, lung, skin, stomach) diseases are discussed. A short account is devoted to the detoxification of heavy metals by chelation via the use of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propane sulfonic acid (DMPS), and penicillamine chelators.
- MeSH
- Antioxidants metabolism MeSH
- Bioaccumulation MeSH
- Environmental Pollutants toxicity MeSH
- Humans MeSH
- Oxidative Stress * drug effects MeSH
- Metals, Heavy * toxicity MeSH
- Environmental Exposure adverse effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
This study evaluated the effects of dietary methionine level and rearing water temperature on growth, antioxidant capacity, methionine metabolism, and hepatocyte autophagy in spotted seabass (Lateolabrax maculatus). A factorial design was used with six methionine levels [0.64, 0.85, 1.11, 1.33, 1.58, and 1.76%] and two temperatures [moderate temperature (MT): 27 °C, and high temperature (HT): 33 °C]. The results revealed the significant effects of both dietary methionine level and water temperature on weight gain (WG) and feed efficiency (FE), and their interaction effect was found on WG (P < 0.05). In both water temperatures tested, fish WG increased with increasing methionine level up to 1.11% and decreased thereafter. The groups of fish reared at MT exhibited dramatically higher WG and FE than those kept at HT while an opposite trend was observed for feed intake. Liver antioxidant indices including reduced glutathione and malondialdehyde (MDA) concentrations, and catalase and superoxide dismutase (SOD) activities remarkably increased in the HT group compared to the MT group. Moreover, the lowest MDA concentration and the highest SOD activity were recorded at methionine levels between 1.11% and 0.85%, respectively, regardless of water temperatures. Expression of methionine metabolism-related key enzyme genes (mat2b, cbs, ms, and bhmt) in the liver was increased at moderate methionine levels, and higher expression levels were detected at MT compared to HT with the exception of ms gene relative expression. Relative expression of hepatocyte autophagy-related genes (pink1, atg5, mul1, foxo3) and hsp70 was upregulated by increasing methionine level up to a certain level and decreased thereafter and increasing water temperature led to significantly enhanced expression of hsp70. In summary, HT induced heat stress and reduced fish growth, and an appropriate dietary methionine level improved the antioxidant capacity and stress resistance of fish. A second-order polynomial regression analysis based on the WG suggested that the optimal dietary methionine level for maximum growth of spotted seabass is 1.22% of the diet at 27 °C and 1.26% of the diet at 33 °C, then 1.37 g and 1.68 g dietary methionine intake is required for 100 g weight gain at 27 °C or 33 °C, respectively.
- MeSH
- Antioxidants MeSH
- Diet veterinary MeSH
- Weight Gain MeSH
- Animal Feed MeSH
- Methionine * pharmacology MeSH
- Bass * MeSH
- Dietary Supplements MeSH
- Racemethionine MeSH
- Superoxide Dismutase MeSH
- Temperature MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
Cisplatin is a widely used chemotherapy drug for the treatment of various cancers. However, although cisplatin is effective in targeting cancer cells, it has severe side effects including skeletal muscle atrophy. In this study, we aimed to characterize the role of Dihydromyricetin in cisplatin-induced muscle atrophy in mice. 5-week-old male C57BL/6 mice were treated with Dihydromyricetin for 14 days orally followed by in intraperitoneally cisplatin administration for 6 days. Gastrocnemius muscles were isolated for the following experiments. Antioxidative stress were determined by peroxidative product malondialdehyde (MDA) and antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Quadriceps muscle mass and grip strength were significantly restored by Dihydromyricetin in a dose-dependent manner. Moreover, muscle fibers were improved in Dihydromyricetin treated group. Excessive skeletal muscle E3 ubiquitin-protein ligases in cisplatin group were significantly repressed by Dihydromyricetin treatment. Dihydromyricetin significantly reduced oxidative stress induced by cisplatin by decreasing MDA level and restored SOD and GPx activities. In addition, ferroptosis was significantly reduced by Dihydromyricetin characterized by reduced iron level and ferritin heavy chain 1 and improved Gpx4 level. The present study demonstrated that Dihydromyricetin attenuated cisplatin-induced muscle atrophy by reducing skeletal muscle E3 ubiquitin-protein ligases, oxidative stress, and ferroptosis.
- MeSH
- Antioxidants pharmacology MeSH
- Cisplatin * toxicity MeSH
- Ferroptosis * drug effects MeSH
- Flavonols * pharmacology therapeutic use MeSH
- Muscle, Skeletal drug effects pathology metabolism MeSH
- Mice, Inbred C57BL * MeSH
- Mice MeSH
- Oxidative Stress * drug effects MeSH
- Antineoplastic Agents toxicity MeSH
- Muscular Atrophy * chemically induced pathology metabolism prevention & control drug therapy MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Several commercially available triorganotin compounds were previously found to function as agonist ligands for nuclear retinoid X receptor (RXR) molecules. Triphenyltin isoselenocyanate (TPT-NCSe), a novel selenium atom containing a derivative of triorganotin origin, was found to represent a new cognate bioactive ligand for RXRs. TPT-NCSe displayed a concentration- and time-dependent decrease in the cell viability in both human breast carcinoma MCF-7 (estrogen receptor positive) and MDA‐MB‐231 (triple negative) cell lines. Reactive oxygen species levels generated in response to TPT-NCSe were significantly higher in both carcinoma cell lines treated with TPT-NCSe when compared to mock-treated samples. Treatment with 500 nM TPT-NCSe caused a decrease in SOD1 and increased SOD2 mRNA in MCF-7 cells. The levels of SOD2 mRNA were more increased following the treatment with TPT-NCSe along with 1 μM all-trans retinoic acid (AtRA) in MCF-7 cells. An increased superoxide dismutase SOD1 and SOD2 mRNA levels were also detected in combination treatment of 500 nM TPT-NCSe and 1 μM AtRA in TPT-NCSe-treated MDA-MB-231 cells. The data have also shown that TPT-NCSe induces apoptosis via a caspase cascade triggered by the mitochondrial apoptotic pathway. TPT-NCSe modulates the expression levels of apoptosis‐related proteins, Annexin A5, Bcl‐2 and BAX family proteins, and finally, it enhances the expression levels of its cognate nuclear receptor subtypes RXRalpha and RXRbeta.
- MeSH
- Apoptosis drug effects MeSH
- Humans MeSH
- Ligands MeSH
- MCF-7 Cells MeSH
- Cell Line, Tumor MeSH
- Breast Neoplasms * drug therapy metabolism pathology MeSH
- Organotin Compounds * pharmacology MeSH
- Organoselenium Compounds pharmacology chemistry MeSH
- Cell Proliferation drug effects MeSH
- Reactive Oxygen Species metabolism MeSH
- Retinoid X Receptors metabolism MeSH
- Superoxide Dismutase-1 metabolism genetics MeSH
- Superoxide Dismutase metabolism MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Farrerol (FA) is a traditional Chinese herbal medicine known for its anti-inflammatory and anti-oxidative properties in various diseases. Ferroptosis is an iron-dependent oxidative stress-induced cell death. It is characterized by lipid peroxidation and glutathione depletion and is involved in neuronal injury. However, the role of FA in inhibiting ferroptosis in hypoxic-ischemic encephalopathy (HIE) and its underlying mechanisms are not yet completely elucidated. This study aimed to investigate whether FA could mediate ferroptosis and explore its function and molecular mechanism in HIE. A neonatal rat model of HIE was used, and rats were treated with FA, ML385 (a specific inhibitor of nuclear factor erythroid 2-related factor 2 [Nrf2]), or a combination of both. Neurological deficits, infarction volume, brain water content, pathological changes, and iron ion accumulation in the brain tissues were measured using the Zea-Longa scoring system and triphenyl tetrazolium chloride (TTC), hematoxylin-eosin (HE), and Perls' staining. The expression levels of GSH-Px, MDA, SOD, and ROS in brain tissues were also evaluated. Western blot analysis was performed to analyze the expression of the Nrf2 pathway and ferroptosis-related proteins. The results showed that FA administration significantly reduced neuronal damage, infarct volume, cerebral edema, and iron ion accumulation and inhibited MDA and ROS levels while promoting GSH-Px and SOD levels. FA also increased the expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), Nrf2, and HO-1. Moreover, the combination of ML385 and FA in HIE abolished the FA protective effects. Therefore, the study concludes that FA exerts a neuroprotective effect after HIE by inhibiting oxidative stress and ferroptosis via the Nrf2 signaling pathway.
Cancer cells have a special energy metabolism that enables them to multiply quickly. Under normal oxygen conditions, the Warburg effect is a distinguishing aspect of cancer metabolism in which anaerobic glycolysis is favored. Enhanced glycolysis also helps to produce nucleotides, amino acids, lipids, and folic acid, all of which are necessary for cancer cell division. In a variety of metabolic processes, including glycolysis, the co-enzyme nicotinamide adenine dinucleotide (NAD) mediates redox reactions. NAD levels that are higher promote glycolysis and supply energy to cancer cells. NAD metabolism, like energy metabolism, is linked in cancer genesis and could be a potential therapeutic target for cancer treatment. In this research, NAD-consuming enzymes, poly(ADP-ribose) polymerase (PARP) and SIRT1, have been investigated in breast cancer patients, in addition to detect the levels of serum malondialdehyde (MDA), superoxide dismutase (SOD) and vitamin K levels. Sixty participants were enrolled in this study, 30 women with breast cancer and 30 controls. Serum were analysed for determination of the levels of PARP1, SIRT1, MDA, SOD, and vitamin K. The results showed a drop in the expression levels of PARP and that was concomitant with the elevation in the expression levels of SIRT1 and MDA, in addition to the drop in SOD and vitamin K levels. These findings suggest that SIRT1 might be the most NAD-consuming enzyme in cancerous cells rather than PARP (the DNA repair enzyme), and this increase in MDA with the drop in SOD and vitamin K might be associated with the increase in cell proliferation and a decrease in apoptotic cell death. Finally, this study could be used as a treatment option for patients with breast cancer. could be used as a treatment option for patients with breast cancer.
- MeSH
- Clinical Laboratory Techniques methods MeSH
- Humans MeSH
- NAD metabolism MeSH
- Biomarkers, Tumor analysis MeSH
- Breast Neoplasms * diagnosis pathology MeSH
- Poly (ADP-Ribose) Polymerase-1 analysis metabolism MeSH
- Sirtuin 1 analysis metabolism MeSH
- Superoxide Dismutase analysis metabolism MeSH
- Vitamin K analysis MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Clinical Study MeSH
Camels are considered an important food source in North Africa. Trypanosomiasis in camels is a life-threatening disease that causes severe economic losses in milk and meat production. Therefore, the objective of this study was to determine the trypanosome genotypes in the North African region. Trypanosome infection rates were determined by microscopic examination of blood smears and polymerase chain reaction (PCR). In addition, total antioxidant capacity (TAC), lipid peroxides (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were determined in erythrocyte lysate. Furthermore, 18S amplicon sequencing was used to barcode and characterizes the genetic diversity of trypanosome genotypes in camel blood. In addition to Trypanosoma, Babesia and Thelieria were also detected in the blood samples. PCR showed that the trypanosome infection rate was higher in Algerian samples (25.7%) than in Egyptian samples (7.2%). Parameters such as MDA, GSH, SOD and CAT had significantly increased in camels infected with trypanosomes compared to uninfected control animals, while TAC level was not significantly changed. The results of relative amplicon abundance showed that the range of trypanosome infection was higher in Egypt than in Algeria. Moreover, phylogenetic analysis showed that the Trypanosoma sequences of Egyptian and Algerian camels are related to Trypanosoma evansi. Unexpectedly, diversity within T. evansi was higher in Egyptian camels than in Algerian camels. We present here the first molecular report providing a picture of trypanosomiasis in camels, covering wide geographical areas in Egypt and Algeria.
- MeSH
- Antioxidants MeSH
- Phylogeny MeSH
- Genotype MeSH
- Superoxide Dismutase genetics MeSH
- Trypanosoma * genetics MeSH
- Trypanosomiasis * epidemiology veterinary MeSH
- Camelus MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Africa, Northern MeSH
The role of glia in amyotrophic lateral sclerosis (ALS) is undeniable. Their disease-related activity has been extensively studied in the spinal cord, but only partly in the brain. We present herein a comprehensive study of glia in the cortex of SOD1(G93A) mice-a widely used model of ALS. Using single-cell RNA sequencing (scRNA-seq) and immunohistochemistry, we inspected astrocytes, microglia, and oligodendrocytes, in four stages of the disease, respecting the factor of sex. We report minimal changes of glia throughout the disease progression and regardless of sex. Pseudobulk and single-cell analyses revealed subtle disease-related transcriptional alterations at the end-stage in microglia and oligodendrocytes, which were supported by immunohistochemistry. Therefore, our data support the hypothesis that the SOD1(G93A) mouse cortex does not recapitulate the disease in patients, and we recommend the use of a different model for future studies of the cortical ALS pathology.
- MeSH
- Amyotrophic Lateral Sclerosis * genetics pathology MeSH
- Spinal Cord pathology MeSH
- Disease Models, Animal MeSH
- Motor Neurons pathology MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Neuroglia * pathology MeSH
- Superoxide Dismutase-1 * genetics MeSH
- Superoxide Dismutase genetics MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: The study was undertaken to evaluate the effect of 6-week supplementation with a daily dose of 2g of curcumin on VO2max and prooxidant/antioxidant homeostasis in middle-aged amateur long-distance runners during the preparatory period of the macrocycle. METHODS: Thirty runners were randomly assigned to a placebo group (PL) and a curcumin-supplemented group (CU). Their VO2max was assessed before supplementation and after 6 weeks of supplementation. Venous blood samples were collected from the participants at rest, immediately after exercise, and after 1h of recovery to evaluate the activity of antioxidant enzymes (SOD, CAT, GPx), non-enzymatic antioxidants (GSH, UA) and sirtuin 3 level (SIRT 3), as well as the levels of oxidative stress markers (TOS/TOC, MDA, and 8-OHdG) and muscle damage markers (CK, LDH, and Mb). RESULTS: VO2max, the activity of enzymatic antioxidants, the concentrations of non-enzymatic antioxidants, the levels of oxidative stress markers, and the levels of muscle damage markers did not change significantly in the CU group over 6 weeks of supplementation with curcumin. However, the resting concentration of SIRT 3 was found to be significantly higher (p ≤ 0.05) compared with pre-supplementation. CONCLUSION: Curcumin supplementation does not have a significant effect on VO2max and prooxidant/antioxidant homeostasis in runners.
- MeSH
- Antioxidants MeSH
- Curcumin * MeSH
- Humans MeSH
- Copper MeSH
- Dietary Supplements MeSH
- Reactive Oxygen Species MeSH
- Sirtuin 3 * MeSH
- Superoxide Dismutase MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
