Induction of autophagy represents an effective survival strategy for nutrient-deprived or stressed cancer cells. Autophagy contributes to the modulation of communication within the tumor microenvironment. Here, we conducted a study of the metabolic and signaling implications associated with autophagy induced by glutamine (Gln) and serum starvation and PI3K/mTOR inhibitor and autophagy inducer NVP-BEZ235 (BEZ) in the head and neck squamous cell carcinoma (HNSCC) cell line FaDu. We compared the effect of these different types of autophagy induction on ATP production, lipid peroxidation, mitophagy, RNA cargo of extracellular vesicles (EVs), and EVs-associated cytokine secretome of cancer cells. Both BEZ and starvation resulted in a decline in ATP production. Simultaneously, Gln starvation enhanced oxidative damage of cancer cells by lipid peroxidation. In starved cells, there was a discernible fragmentation of the mitochondrial network coupled with an increase in the presence of tumor susceptibility gene 101 (TSG101) on the mitochondrial membrane, indicative of the sorting of mitochondrial cargo into EVs. Consequently, the abundance of mitochondrial RNAs (mtRNAs) in EVs released by FaDu cells was enhanced. Notably, mtRNAs were also detectable in EVs isolated from the serum of both HNSCC patients and healthy controls. Starvation and BEZ reduced the production of EVs by cancer cells, yet the characteristic molecular profile of these EVs remained unchanged. We also found that alterations in the release of inflammatory cytokines constitute a principal response to autophagy induction. Importantly, the specific mechanism driving autophagy induction significantly influenced the composition of the EVs-associated cytokine secretome.
- MeSH
- Adenosine Triphosphate * metabolism MeSH
- Autophagy * drug effects MeSH
- Squamous Cell Carcinoma of Head and Neck metabolism genetics pathology MeSH
- Extracellular Vesicles * metabolism drug effects MeSH
- Glutamine * metabolism MeSH
- Humans MeSH
- Mitochondria metabolism MeSH
- Cell Line, Tumor MeSH
- Head and Neck Neoplasms metabolism pathology genetics MeSH
- Oxidative Stress * MeSH
- RNA, Mitochondrial * metabolism genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Oxidative stress status, as a disruption of redox homeostasis, in the blood sera of Wistar rats caused by repeated application of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, K074, and K075 were evaluated. Throughout this study, each oxime in a dose of 0.1 of LD50/kg im was given 2x/week for 4 weeks. Then, seven days after the last oximes' application, markers of lipid peroxidation (malondialdehyde, MDA), and protein oxidation (advanced oxidation protein products, AOPP), as well as the activity of antioxidant enzymes (catalase, CAT, superoxide dismutase, SOD, reduced glutathione, GSH, and oxidized glutathione, GSSG), were determined. Oxidative stress parameters, MDA and AOPP were significantly highest in the K048-, K074- and K075-treated groups (p < 0.001). The activity of CAT was significantly elevated in the obidoxime-treated group (p < 0.05), while treatment with K027, K048, and K074 induced high elevation in SOD levels (p < 0.01, p < 0.001). Interestingly, the activity of GSH in each oxime-treated group was significantly elevated. Unlike, treatment with obidoxime caused elevation in GSSG levels (p < 0.01). As a continuation of our previously published data, these results assure that applied oximes following subacute treatment ameliorated the oxidative status and further adverse systemic toxic effects in rats.
- MeSH
- Antioxidants metabolism pharmacology MeSH
- Biomarkers * blood MeSH
- Glutathione * blood metabolism MeSH
- Catalase metabolism blood MeSH
- Rats MeSH
- Malondialdehyde blood metabolism MeSH
- Oxidative Stress * drug effects MeSH
- Oximes * pharmacology MeSH
- Lipid Peroxidation drug effects MeSH
- Rats, Wistar * MeSH
- Advanced Oxidation Protein Products blood MeSH
- Cholinesterase Reactivators pharmacology MeSH
- Superoxide Dismutase metabolism blood MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Background: Recent evidence has shown that circulating microribonucleic acid (miRNA) has been related to many diseases either as an inhibitor or a stimulant factor, among them miRNA-122 which has proven through studies its relationship with insulin resistance, an adversative lipid profile, obesity, type 2 diabetes, and metabolic syndrome in several studies; however, the mechanisms involved are unknown. This study investigates the role of miRNA-122 expression in overweight patients suffering from metabolic disorders such as diabetes and hypertension and its relationship to the development of oxidative stress in patient groups.Materials and Methods: 30 patients with type 2 diabetes mellitus (T2DM), 30 people with hypertension (HTN), 30 patients with T2DM+HTN, and 30 healthy persons who served as controls were enrolled in this study. An ARCHITECT c4000 clinical chemistry analyzer was used to assess lipid profiles. The sandwich immunodetection approach was used to assess whole blood hemoglobinA1c. By colorimetric methodology, catalase activity (CAT), superoxide dismutase activity (SOD), malondialdehyde (MDA) levels, and advanced oxidation protein products (AOPPs) levels were measured. The expression of serum miRNA-122 was determined using the quantitative polymerase chain reaction.Results: The activity of SOD and CAT in patient groups was found to be substantially lower than in the control group (p < 0.05), whereas MDA and AOPP concentrations were found to be significantly higher in patient groups compared to the control group (p < 0.05). When patient groups were compared to control groups, the miRNA-122 level was higher in the patients (p< 0.05).Conclusions: miRNA-122 expression is involved in the pathogenesis of T2DM and HTN-induced oxidative stress, there is a reciprocal relationship between the increase in gene expression of the miRNA-122 and the increase in oxidative stress accompanied by a decrease in the effectiveness of antioxidant enzymes, which leads to the development of the disease.
- MeSH
- Blood Chemical Analysis methods instrumentation statistics & numerical data MeSH
- Biomarkers blood MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Malondialdehyde blood MeSH
- Metabolic Diseases * blood pathology MeSH
- MicroRNAs * blood MeSH
- Oxidative Stress MeSH
- Advanced Oxidation Protein Products blood MeSH
- Superoxide Dismutase blood MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Publication type
- Clinical Study MeSH
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production and elimination is termed oxidative stress, a critical factor and common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic diseases, neurological disorders (Alzheimer's and Parkinson's diseases), and other disorders. To counteract the harmful effects of ROS, organisms have evolved a complex, three-line antioxidant defense system. The first-line defense mechanism is the most efficient and involves antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). This line of defense plays an irreplaceable role in the dismutation of superoxide radicals (O2•-) and hydrogen peroxide (H2O2). The removal of superoxide radicals by SOD prevents the formation of the much more damaging peroxynitrite ONOO- (O2•- + NO• → ONOO-) and maintains the physiologically relevant level of nitric oxide (NO•), an important molecule in neurotransmission, inflammation, and vasodilation. The second-line antioxidant defense pathway involves exogenous diet-derived small-molecule antioxidants. The third-line antioxidant defense is ensured by the repair or removal of oxidized proteins and other biomolecules by a variety of enzyme systems. This review briefly discusses the endogenous (mitochondria, NADPH, xanthine oxidase (XO), Fenton reaction) and exogenous (e.g., smoking, radiation, drugs, pollution) sources of ROS (superoxide radical, hydrogen peroxide, hydroxyl radical, peroxyl radical, hypochlorous acid, peroxynitrite). Attention has been given to the first-line antioxidant defense system provided by SOD, CAT, and GPx. The chemical and molecular mechanisms of antioxidant enzymes, enzyme-related diseases (cancer, cardiovascular, lung, metabolic, and neurological diseases), and the role of enzymes (e.g., GPx4) in cellular processes such as ferroptosis are discussed. Potential therapeutic applications of enzyme mimics and recent progress in metal-based (copper, iron, cobalt, molybdenum, cerium) and nonmetal (carbon)-based nanomaterials with enzyme-like activities (nanozymes) are also discussed. Moreover, attention has been given to the mechanisms of action of low-molecular-weight antioxidants (vitamin C (ascorbate), vitamin E (alpha-tocopherol), carotenoids (e.g., β-carotene, lycopene, lutein), flavonoids (e.g., quercetin, anthocyanins, epicatechin), and glutathione (GSH)), the activation of transcription factors such as Nrf2, and the protection against chronic diseases. Given that there is a discrepancy between preclinical and clinical studies, approaches that may result in greater pharmacological and clinical success of low-molecular-weight antioxidant therapies are also subject to discussion.
- MeSH
- Anthocyanins metabolism pharmacology MeSH
- Antioxidants * pharmacology metabolism MeSH
- Chronic Disease MeSH
- Peroxynitrous Acid pharmacology MeSH
- Humans MeSH
- Neoplasms * MeSH
- Nitric Oxide MeSH
- Oxidative Stress MeSH
- Hydrogen Peroxide MeSH
- Reactive Oxygen Species metabolism MeSH
- Superoxide Dismutase metabolism MeSH
- Superoxides MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Contractile dysfunction and fatal arrhythmias are the hallmarks of myocardial ischemia/reperfusion (I/R) injury. Pterostilbene has notable cardioprotective effects, but its main mechanisms are not fully understood. Here, we investigated the effect of PTE on myocardial hemodynamics, arrhythmias, inflammatory/oxidative responses, and the causal role of the JAK2/STAT3 pathway in rats with acute myocardial I/R injury. Sixty male 7-8 months Sprague-Dawley rats (n=10/each group) experienced in vivo model of myocardial I/R injury through 40-min LAD coronary artery occlusion and subsequent 24-h reperfusion. PTE at concentrations of 5 and 25 mg/kg was intraperitoneally administered to rats five min before reperfusion. Cardiac hemodynamics, reperfusion-induced ventricular arrhythmias, infarct size, inflammatory cytokines, oxidative stress markers, the activity of the JAK2/STAT3 pathway were measured as the endpoints. Administration of PTE to I/R-injured rats recovered myocardial contractile function and reduced infarct size and ventricular arrhythmias counts and incidence in a dose-dependent manner. PTE at 25 mg/kg significantly and more potently reduced the levels of inflammatory mediators NF-?B, TNF-?, and IL-1?, suppressed intracellular ROS production, augmented the activity of glutathione, and manganese-superoxide dismutase, and upregulated the JAK2 and STAT3 phosphorylation. Importantly, pretreatment of rats with Ag490 as a JAK2 inhibitor significantly abolished the cardioprotective and signaling effects of PTE in I/R rats. PTE exerts significant protective effects on reducing arrhythmias and myocardial infarction and enhancing cardiac function by stimulating JAK2/STAT3-related suppression of inflammatory and oxidative reactions in the I/R injury setting.
- MeSH
- Apoptosis MeSH
- Cytokines MeSH
- Glutathione MeSH
- Myocardial Infarction * metabolism MeSH
- Interleukin-1 pharmacology MeSH
- Janus Kinase 2 MeSH
- Rats MeSH
- Manganese MeSH
- Inflammation Mediators MeSH
- Rats, Sprague-Dawley MeSH
- Reactive Oxygen Species MeSH
- Myocardial Reperfusion Injury * metabolism MeSH
- Reperfusion Injury * metabolism MeSH
- Stilbenes MeSH
- Superoxide Dismutase metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
N-acetylcysteine (NAC), often used as an antioxidant-scavenging reactive oxygen species (ROS) in vitro, was recently shown to increase the cytotoxicity of other compounds through ROS-dependent and ROS-independent mechanisms. In this study, NAC itself was found to induce extensive ROS production in human leukemia HL-60 and U937 cells. The cytotoxicity depends on ROS-modulating enzyme expression. In HL-60 cells, NAC activated NOX2 to produce superoxide (O2•-). Its subsequent conversion into H2O2 by superoxide dismutase 1 and 3 (SOD1, SOD3) and production of ClO- from H2O2 by myeloperoxidase (MPO) was necessary for cell death induction. While the addition of extracellular SOD potentiated NAC-induced cell death, extracellular catalase (CAT) prevented cell death in HL-60 cells. The MPO inhibitor partially reduced the number of dying HL-60 cells. In U937 cells, the weak cytotoxicity of NAC is probably caused by lower expression of NOX2, SOD1, SOD3, and by the absence of MOP expression. However, even here, the addition of extracellular SOD induced cell death in U937 cells, and this effect could be reversed by extracellular CAT. NAC-induced cell death exhibited predominantly apoptotic features in both cell lines. Conclusions: NAC itself can induce extensive production of O2•- in HL-60 and U937 cell lines. The fate of the cells then depends on the expression of enzymes that control the formation and conversion of ROS: NOX, SOD, and MPO. The mode of cell death in response to NAC treatment bears apoptotic and apoptotic-like features in both cell lines.
- MeSH
- Acetylcysteine pharmacology MeSH
- HL-60 Cells MeSH
- Catalase genetics MeSH
- Leukemia drug therapy genetics metabolism MeSH
- Humans MeSH
- NADPH Oxidase 2 genetics MeSH
- Oxidative Stress drug effects MeSH
- Peroxidase genetics MeSH
- Cell Proliferation drug effects MeSH
- Reactive Oxygen Species metabolism MeSH
- Gene Expression Regulation, Neoplastic drug effects MeSH
- Gene Expression Profiling MeSH
- Superoxide Dismutase genetics MeSH
- U937 Cells MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Oxidative status has been proposed as an important ecological and evolutionary force given that pro-oxidant metabolites damage molecules, cells and tissues, with fitness consequences for organisms. Consequently, organisms usually face a trade-off between regulating their oxidative status and other physiological traits. However, environmental stressors and the availability of dietary-derived antioxidants vary according to local conditions and, thus, organisms inhabiting different habitats face different oxidative pressures. Still, there is little information on how different environmental conditions influence the oxidative status of animals inhabiting terrestrial environments. In this work, we examined the variation in oxidative status in the blue tit (Cyanistes caeruleus), a bird species with hatching asynchrony. Specifically, we examined the oxidative status of the largest and the smallest nestlings in the brood, inhabiting four forests differing in food availability and ectoparasite prevalence. We measured lipid peroxidation (malondialdehyde; MDA) as a marker of oxidative damage, total antioxidant capacity (Trolox-equivalent antioxidant capacity; TEAC) and antioxidant enzymatic activity (catalase, glutathione S-transferase, glutathione peroxidase) in blood samples. The glutathione peroxidase (GPX) activity differed among the forests, being the highest in the pine forest and the lowest in a mixed oak (Quercus) forest in the most humid area. Lipid peroxidation was higher in larger nestlings, suggesting higher oxidative damage with an increasing growth rate. Neither brood size, laying date, nor ectoparasites were related to the oxidative status of nestlings. These results suggest that nest rearing conditions might shape the oxidative status of birds, having consequences for habitat-dependent variation in regulation of oxidative status.
- MeSH
- Antioxidants metabolism MeSH
- Diet * MeSH
- Ecosystem * MeSH
- Glutathione Peroxidase metabolism MeSH
- Catalase metabolism MeSH
- Malondialdehyde metabolism MeSH
- Oxidation-Reduction MeSH
- Oxidative Stress physiology MeSH
- Passeriformes physiology MeSH
- Lipid Peroxidation MeSH
- Geography MeSH
- Songbirds physiology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Spain MeSH
The adipokinetic hormones (AKHs) are known to be involved in insect immunity, thus their role in the cockroach Periplaneta americana infected with the entomopathogenic fungus Isaria fumosorosea was examined in this study. The application of I. fumosorosea resulted in a significant increase in both Akh gene expression and AKH peptide levels. Further, co-application of I. fumosorosea with Peram-CAH-II significantly enhanced cockroach mortality compared with the application of I. fumosorosea alone. The mechanism of AKH action could involve metabolic stimulation, which was indicated by a significant increase in carbon dioxide production; this effect can increase the turnover and thus efficacy of toxins produced by I. fumosorosea in the cockroach's body. I. fumosorosea treatment resulted in a significant decrease in haemolymph nutrients (carbohydrates and lipids), but co-application with Peram-CAH-II restored control level of lipids or even further increased the level of carbohydrates. Such nutritional abundance could enhance the growth and development of I. fumosorosea. Further, both I. fumosorosea and Peram-CAH-II probably affected oxidative stress: I. fumosorosea alone curbed the activity of catalase in the cockroach's gut, but co-application with Peram-CAH-II stimulated it. Interestingly, the hormone alone had no effect on catalase activity. Taken together, the results of the present study demonstrate the interactions between the fungus and AKH activity; understanding this relationship could provide insight into AKH action and may have practical implications for insect pest control in the future.
- MeSH
- Insect Control methods MeSH
- Insect Hormones pharmacology MeSH
- Catalase metabolism MeSH
- Pyrrolidonecarboxylic Acid analogs & derivatives pharmacology MeSH
- Oligopeptides pharmacology MeSH
- Carbon Dioxide metabolism MeSH
- Oxidative Stress MeSH
- Periplaneta drug effects MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
L-arginine is a substrate for nitric oxide synthase (NOS) responsible for the production of NO. This investigation studied the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on L-arginine induced oxidative stress and hypotension. Forty Wistar-Kyoto rats were treated for 14 days with vehicle, L-arginine (12.5mg/ml p.o.), L-arginine+apocynin (2.5mmol/L p.o.), L-arginine+catalase (10000U/kg/day i.p.) and L-arginine plus apocynin+catalase respectively. Weekly renal functional and hemodynamic parameters were measured and kidneys harvested at the end of the study for histopathological and renal NADPH oxidase 4 (Nox4) assessments. L-arginine administration in normotensive rats decreased systolic blood pressure (120±2 vs 91±2mmHg) and heart rate (298±21 vs 254±15b/min), enhanced urinary output (21.5±4.2 vs 32±1.9ml/24h , increased creatinine clearance (1.72±0.56 vs 2.62±0.40ml/min/kg), and fractional sodium excretion (0.88±0.16 vs 1.18±0.16 %), caused proteinuria (28.10±1.93 vs 35.26±1.69mg/kg/day) and a significant decrease in renal cortical blood perfusion (292±3 vs 258±5bpu) and pulse wave velocity (3.72±0.20 vs 2.84±0.13m/s) (all P<0.05). L-arginine increased plasma malondialdehyde (by ~206 % P<0.05) and NO (by~51 %, P<0.05) but decreased superoxide dismutase (by~31 %, P<0.05) and total antioxidant capacity (by~35 %, P<0.05) compared to control. Renal Nox4 mRNA activity was approximately 2.1 fold higher (P<0.05) in the L-arginine treated rats but was normalized by apocynin and apocynin plus catalase treatment. Administration of apocynin and catalase, but not catalase alone to rats fed L-arginine, restored the deranged renal function and structure, prevented hypotension and enhanced the antioxidant capacity and suppressed Nox4 expression. These findings suggest that apocynin and catalase might be used prophylactically in states of oxidative stress.
- MeSH
- Acetophenones pharmacology MeSH
- Pulse Wave Analysis methods MeSH
- Antioxidants pharmacology MeSH
- Arginine pharmacology MeSH
- Hypotension chemically induced drug therapy metabolism pathology MeSH
- Catalase pharmacology MeSH
- Blood Pressure drug effects MeSH
- Rats MeSH
- Kidney drug effects metabolism pathology MeSH
- Disease Models, Animal MeSH
- NADPH Oxidase 4 metabolism MeSH
- Oxidative Stress drug effects MeSH
- Rats, Inbred WKY MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The detrimental effects of organophosphates (OPs) on human health are thought to be of systemic, i.e., irreversible inhibition of acetylcholinesterase (AChE) at nerve synapses. However, several studies have shown that AChE inhibition alone cannot explain all the toxicological manifestations in prolonged exposure to OPs. The present study aimed to assess the status of antioxidants malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) (reduced), catalase, and ferric reducing antioxidant power (FRAP) in chronic OP-exposed groups from Cameroon and Pakistan. Molecular analysis of genetic polymorphisms (SNPs) of glutathione transferases (GSTM1, GSTP1, GSTT1), catalase gene (CAT, rs7943316), sirtuin 1 gene (SIRT1, rs10823108), acetylcholinesterase gene (ACHE, rs2571598), and butyrylcholinesterase gene (BCHE, rs3495) were screened in the OP-exposed individuals to find the possible causative association with oxidative stress and toxicity. Cholinesterase and antioxidant activities were measured by colorimetric methods using a spectrophotometer. Salting-out method was employed for DNA extraction from blood followed by restriction fragment length polymorphism (RFLP) for molecular analysis. Cholinergic enzymes were significantly decreased in OP-exposed groups. Catalase and SOD were decreased and MDA and FRAP were increased in OP-exposed groups compared to unexposed groups in both groups. GSH was decreased only in Pakistani OPs-exposed group. Molecular analysis of ACHE, BCHE, Catalase, GSTP1, and GSTM1 SNPs revealed a tentative association with their phenotypic expression that is level of antioxidant and cholinergic enzymes. The study concludes that chronic OPs exposure induces oxidative stress which is associated with the related SNP polymorphism. The toxicogenetics of understudied SNPs were examined for the first time to our understanding. The findings may lead to a newer area of investigation on OPs induced health issues and toxicogenetics.
- MeSH
- Acetylcholinesterase genetics MeSH
- Butyrylcholinesterase genetics MeSH
- Adult MeSH
- Glutathione S-Transferase pi genetics MeSH
- Glutathione MeSH
- Glutathione Transferase genetics MeSH
- GPI-Linked Proteins genetics MeSH
- Gene-Environment Interaction * MeSH
- Polymorphism, Single Nucleotide * MeSH
- Catalase genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Malondialdehyde MeSH
- Adolescent MeSH
- Young Adult MeSH
- Organophosphorus Compounds adverse effects MeSH
- Oxidative Stress genetics MeSH
- Sirtuin 1 genetics MeSH
- Environmental Exposure adverse effects analysis MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Cameroon MeSH
- Pakistan MeSH
