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Acetaminophen

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Acetaminophen (AAP) which broadly used as an antipyretic and analgesic drug is one reason for hepatotoxicity in humans and experimental animals at high doses(32). The toxic metabolite of APP that produced in liver by the cytochrome P450 pathway is named NAPQI(6) that conjugated with glutathione for excretion in the urine. The AAP overdose cause to glutathione depletion that leads to NAPQI accumulation and mitochondrial dysfunction(33). Glutathione depletion promotes the tumor necrosis factor alpha (TNFα) that leads to production of oxygen free radicals from NADPH oxidase and hepatotoxicity finally(34). The AAP is a potential trigger of cytochrome P450 that induced the high reactive quinone-imine production. This matches with sulphahydryl groups in proteins and result in rapid depletion to intracellular glutathione(35). Generally, one parts of the potential intracellular antioxidant defensive system is glutathione that consumes the singlet oxygen, superoxide and hydroxyl radicals(36). Enhancing of intracellular flux of oxygen free radicals results from glutathione depletion leads to oxidative stress in hepatocytes(36). The increasing the serum levels of GOT, GPT and ALP have been attributed to the structural integrity hepatic damage(37). In liver tissue, GOT and GPT are located in cytosol and mitochondria. In following of liver damage, hepatocyte transport function disturbed…show more content…
Main compounds of the enzymatic antioxidant system are three, namely, SOD, CAT and tT which have an important role in detoxifying of H2O2 and superoxide anion in cells. Ample of hepatotoxic drugs induces the liver damage by lipid peroxidation indirectly or directly. The proxy radicals are main factors that mediate lipid peroxidation leading to liver injury and kidney damage(41). MDA as a main reactive aldehyde appears during polyunsaturated fatty acid peroxidation in the biological
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