Xenobiotic Bioactivation-Mediated Cellular Damages
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Besides natural toxins, many toxicities are resulted from metabolic activation of foreign compounds that leads to the formation of reactive intermediate species and metabolites. Oxidative stresses generated from xenobiotic metabolism are potentially capable of interacting with endogenous targets, triggering perturbation in cellular functions and resulting in cellular damages. Covalent binding of reactive intermediates to cellular components results in forming protein and DNA adducts and causing lipid peroxidation. The extent of foreign compound toxicities depends on its nature, metabolic enzymes, and environmental factors and includes natural toxicity, bioactivation-mediated toxicity, and induced toxicity. Xenobiotic bioactivation-mediated cellular damages also include mitochondrial function intervention, interference with ion transporters and enzymatic functions, and immune suppression and stimulation effects. Due to the generation of toxic reactive intermediate in the course of drug metabolism, adverse drug reactions are an important research area.