A Common Feature of Pesticides: Oxidative Stress-The Role of Oxidative Stress in Pesticide-Induced Toxicity.
Ontology highlight
ABSTRACT:
SUBMITTER: Sule RO
PROVIDER: S-EPMC8791758 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Organismal life encounters reactive oxidants from internal metabolism and environmental toxicant exposure. Reactive oxygen and nitrogen species cause oxidative stress and are traditionally viewed as being harmful. On the other hand, controlled production of oxidants in normal cells serves useful purposes to regulate signaling pathways. Reactive oxidants are counterbalanced by complex antioxidant defense systems regulated by a web of pathways to ensure that the response to oxidants is adequate for the body's needs. A recurrent theme in oxidant signaling and antioxidant defense is reactive cysteine thiol-based redox signaling. The nuclear factor erythroid 2-related factor 2 (Nrf2) is an emerging regulator of cellular resistance to oxidants. Nrf2 controls the basal and induced expression of an array of antioxidant response element-dependent genes to regulate the physiological and pathophysiological outcomes of oxidant exposure. This review discusses the impact of Nrf2 on oxidative stress and toxicity and how Nrf2 senses oxidants and regulates antioxidant defense.
| S-EPMC4680839 | biostudies-literature
Project description:Autophagy is a cellular self-digestion process that mediates protein quality control and serves to protect against neurodegenerative disorders, infections, inflammatory diseases and cancer. Current evidence suggests that autophagy can selectively remove damaged organelles such as the mitochondria. Mitochondria-induced oxidative stress has been shown to play a major role in a wide range of pathologies in several organs, including the heart. Few studies have investigated whether enhanced autophagy can offer protection against mitochondrially-generated oxidative stress. We induced mitochondrial stress in cardiomyocytes using antimycin A (AMA), which increased mitochondrial superoxide generation, decreased mitochondrial membrane potential and depressed cellular respiration. In addition, AMA augmented nuclear DNA oxidation and cell death in cardiomyocytes. Interestingly, although oxidative stress has been proposed to induce autophagy, treatment with AMA did not result in stimulation of autophagy or mitophagy in cardiomyocytes. Our results showed that the MTOR inhibitor rapamycin induced autophagy, promoted mitochondrial clearance and protected cardiomyocytes from the cytotoxic effects of AMA, as assessed by apoptotic marker activation and viability assays in both mouse atrial HL-1 cardiomyocytes and human ventricular AC16 cells. Importantly, rapamycin improved mitochondrial function, as determined by cellular respiration, mitochondrial membrane potential and morphology analysis. Furthermore, autophagy induction by rapamycin suppressed the accumulation of ubiquitinylated proteins induced by AMA. Inhibition of rapamycin-induced autophagy by pharmacological or genetic interventions attenuated the cytoprotective effects of rapamycin against AMA. We propose that rapamycin offers cytoprotection against oxidative stress by a combined approach of removing dysfunctional mitochondria as well as by degrading damaged, ubiquitinated proteins. We conclude that autophagy induction by rapamycin could be utilized as a potential therapeutic strategy against oxidative stress-mediated damage in cardiomyocytes.
| S-EPMC3590254 | biostudies-other
Project description:Mechanisms of estrogen-induced tumorigenesis in the target organ are not well understood. It has been suggested that oxidative stress resulting from metabolic activation of carcinogenic estrogens plays a critical role in estrogen-induced carcinogenesis. We tested this hypothesis by using an estrogen-induced hamster renal tumor model, a well established animal model of hormonal carcinogenesis. Hamsters were implanted with 17beta-estradiol (betaE2), 17alpha-estradiol (alphaE2), 17alpha-ethinylestradiol (alphaEE), menadione, a combination of alphaE2 and alphaEE, or a combination of alphaEE and menadione for 7 months. The group treated with betaE2 developed target organ specific kidney tumors. The kidneys of hamsters treated with alphaE2, alphaEE, or menadione alone did not show any gross evidence of tumor. Kidneys of hamsters treated with a combination of alphaE2 and alphaEE showed early signs of proliferation in the interstitial cells. Kidneys of hamsters treated with a combination of menadione and alphaEE showed foci of tumor with congested tubules and atrophic glomeruli. betaE2-treated tumor-bearing kidneys showed >2-fold increase in 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) levels compared with untreated controls. Kidneys of hamsters treated with a combination of menadione and alphaEE showed increased 8-iso-PGF(2alpha) levels compared with untreated controls, whereas no increase in 8-iso-PGF(2alpha) was detected in kidneys of alphaEE-treated group. A chemical known to produce oxidative stress or a potent estrogen with poor ability to produce oxidative stress, were nontumorigenic in hamsters, when given as single agents, but induced renal tumors, when given together. Thus, these data provide evidence that oxidant stress plays a crucial role in estrogen-induced carcinogenesis.
| S-EPMC153022 | biostudies-literature
Project description:Apigenin, a component in daily diets, demonstrates antioxidant and anti-inflammatory properties. Here, we intended to explore the mechanism of apigenin-mediated endotoxin-induced myocardial injury and its role in the interplay among inflammation, oxidative stress, and autophagy. In our lipopolysaccharide- (LPS-) induced myocardial injury model, apigenin ameliorated cardiac injury (lactate dehydrogenase (LDH) and creatine kinase (CK)), cell death (TUNEL staining, DNA fragmentation, and PARP activity), and tissue damage (cardiac troponin I (cTnI) and cardiac myosin light chain-1 (cMLC1)) and improved cardiac function (ejection fraction (EF) and end diastolic left ventricular inner dimension (LVID)). Apigenin also alleviated endotoxin-induced myocardial injury by modulating oxidative stress (nitrotyrosine and protein carbonyl) and inflammatory cytokines (TNF-?, IL-1?, MIP-1?, and MIP-2) along with their master regulator NF?B. Apigenin modulated redox homeostasis, and its anti-inflammatory role might be associated with its ability to control autophagy. Autophagy (determined by LAMP1, ATG5, and p62), its transcriptional regulator transcription factor EB (TFEB), and downstream target genes including vacuolar protein sorting-associated protein 11 (Vps11) and microtubule-associated proteins 1A/1B light chain 3B (Map1lc3) were modulated by apigenin. Thus, our study demonstrated that apigenin may lead to potential development of new target in sepsis treatment or other myocardial oxidative and/or inflammation-induced injuries.
| S-EPMC5554558 | biostudies-literature
Project description:BackgroundSnakebites remain a major life-threatening event worldwide. It is still difficult to make a positive identification of snake species by clinicians in both Western medicine and Chinese medicine. The main reason for this is a shortage of diagnostic biomarkers and lack of knowledge about pathways of venom-induced toxicity. In traditional Chinese medicine, snakebites are considered to be treated with wind, fire, and wind-fire toxin, but additional studies are required.MethodsCases of snakebite seen at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were grouped as follows: fire toxin - including four cases of bites by Agkistrodon acutus and three bites by Trimeresurus stejnegeri - and wind-fire toxin - four cases of bites by vipers and three bites by cobras. Serum protein quantification was performed using LC-MS/MS. Differential abundance proteins (DAPs) were identified from comparison of snakebites of each snake species and healthy controls. The protein interaction network was constructed using STITCH database.ResultsPrincipal component analysis and hierarchical clustering of 474 unique proteins exhibited protein expression profiles of wind-fire toxins that are distinct from that of fire toxins. Ninety-three DAPs were identified in each snakebite subgroup as compared with healthy control, of which 38 proteins were found to have significantly different expression levels and 55 proteins displayed no expression in one subgroup, by subgroup comparison. GO analysis revealed that the DAPs participated in bicarbonate/oxygen transport and hydrogen peroxide catabolic process, and affected carbon-oxygen lyase activity and heme binding. Thirty DAPs directly or indirectly acted on hydrogen peroxide in the interaction network of proteins and drug compounds. The network was clustered into four groups: lipid metabolism and transport; IGF-mediated growth; oxygen transport; and innate immunity.ConclusionsOur results show that the pathways of snake venom-induced toxicity may form a protein network of antioxidant defense by regulating oxidative stress through interaction with hydrogen peroxide.
| S-EPMC7574533 | biostudies-literature
Project description:Solute carrier (SLC) transporters regulate amino acids, glucose, ions, and metabolites that flow across cell membranes. In the brain, SLCs are the key regulators of neurotransmission, in particular, the glutamate/GABA-glutamine (GGG) cycle. Genetic mutations in SLCs are associated with various neurodevelopmental and neurodegenerative diseases. In this study, we have investigated the role of SLC38A10 under acute oxidative and glutamate stress in mouse primary cortical cells from SLC38A10 knockout (KO) mice. The ER/golgi localized transporter, SLC38A10, transports glutamate, glutamine, and alanine in brain cells, and the aim of this study was to determine the possible effects of removal of SLC38A10 in primary cortical cells under glutamate and oxidative challenges. Primary cortical neuronal cultures of wild-type (WT) cell and SLC38A10 KO mice were subjected to different concentrations of glutamate and hydrogen peroxide. There was no morphological change observed between KO and WT cortical neurons in culture. Interestingly, KO cells showed significantly lower cell viability and higher cell death compared to WT cells under both glutamate and hydrogen peroxide exposure. Further, we evaluated the possible role of p53 in neuronal cell apoptosis in KO cells. We found decreased intracellular p53 protein levels under glutamate and hydrogen peroxide treatment in KO cortical cells. In contrast, caspase 3/7 activity remains unaltered under all conditions. These results demonstrate an indirect relationship between the expression of SLC38A10 and p53 and a role in the cell defense mechanism against neurotoxicity.
| S-EPMC8133219 | biostudies-literature
Project description:Zearalenone are widely occurring food contaminants that cause hepatotoxicity. This research work aimed to investigate how zerumbone, a plant-derived dietary compound, can fight ZEA-induced hepatotoxicity. ZER is found to increase the cells' toxin resistance. This study was performed on mice challenged with ZEA. The administration of ZER decreased the level of alkaline phosphatase and alanine aminotransferase (ALT). Simultaneously, ZER attenuated the inflammatory response via significantly reducing the levels of pro-inflammatory factors, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in serum. Pretreatment with ZER reduced the hepatic malondialdehyde (MDA) concentration, as well as the depletion of hepatic superoxide dismutase (SOD), hepatic glutathione (GSH), and hepatic catalase (CAT). Moreover, it significantly ameliorated ZEA-induced liver damage and histological hepatocyte changes. ZER also relieved ZEA-induced apoptosis by regulating the PI3K/AKT pathway and Nrf2 and HO-1 expression. Furthermore, ZER increasingly activated Bcl2 and suppressed apoptosis marker proteins. Our findings suggest that ZER exhibits the ability to prevent ZEA-induced liver injury and present the underlying molecular basis for potential applications of ZER to cure liver injuries.
| S-EPMC8533127 | biostudies-literature
Project description:Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ?98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg-1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.
| S-EPMC4955191 | biostudies-literature
Project description:In the present work, we indicate that copper is involved in the senescence of human diploid fibroblasts and we describe mechanisms to explain it. Using different techniques, we show for the first time an accumulation of copper in cells during replicative senescence. This accumulation seems to be co-localized with lipofuscin. Second, we observed that an incubation of cells with copper sulfate induced oxidative stress, antioxidant response and premature senescence. Antioxidant molecules reduced the appearance of premature senescence. Third, we found that Nrf2 transcription factor was activated and regulated the expression of genes involved in antioxidant response while p38(MAPK) regulated the appearance of premature senescence.
| S-EPMC3824981 | biostudies-literature
Project description:At present, there are few studies focused on the relationship between copper (Cu) and oxidative stress, apoptosis, or inflammatory responses in animal and human lungs. This study was conducted to explore the effects of Cu on pulmonary oxidative stress, apoptosis and inflammatory responses in mice orally administered with 0 mg/kg (control), 10 mg/kg, 20 mg/kg, and 40 mg/kg of CuSO4 for 42 days. The results showed that CuSO4 increased ROS production, and MDA, 8-OHdG and NO contents as well as iNOS activities and mRNA expression levels. Meanwhile, CuSO4 reduced the activities and mRNA expression levels of antioxidant enzymes (GSH-Px, CAT, and SOD) and GSH contents, and ASA and AHR abilities. Also, CuSO4 induced apoptosis, which was accompanied by decreasing Bcl-2, Bcl-xL mRNA expression levels and protein expression levels, and increasing Bax, Bak, cleaved-caspase-3, cleaved-caspase-9 mRNA, and protein expression levels, and Bax/Bcl-2 ratio. Concurrently, CuSO4 caused inflammation by increasing MPO activities and activating the NF-?B signalling pathway, and down-regulating the mRNA and protein expression levels of anti-inflammatory cytokines (IL-2, IL-4, IL-10). In conclusion, the abovementioned findings demonstrated that over 10 mg/kg CuSO4 can cause oxidative stress, apoptosis, and inflammatory responses, which contribute to pulmonary lesions and dysfunction in mice.
| S-EPMC7521514 | biostudies-literature