Reactive Intermediates Generated from Bioactivation
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The increased toxicity of metabolic intermediates or metabolites is primarily the results of the conversion of xenobiotics into chemically reactive species such as reactive oxygen/nitrogen species, free radicals, or positively or neutral charged electrophiles. Electrophilic intermediates are consisted of nonionic and cationic species. Nonionic electrophilic intermediates are such as aldehydes, ketones, epoxides, quinones, sulfoxides, nitroso compounds, and acyl halides, while cationic electrophilic intermediates include carbonium ions and nitrenium ions. Chemically reactive species can interact with proteins, DNA, and lipids, leading to protein adducts, DNA adducts, and lipid peroxidation.