Drug-Induced Hepatotoxicity

Abstract

This chapter aims at discussing the consequential effects of drug-induced hepatotoxicity on man. The liver carries out drug detoxification among other roles, but sometimes, drug toxicity can occur caused by either medication overdose or imbalance drug metabolic reactions (Phase 1 & 2), resulting in the formation of reactive (toxic) metabolites (electrophilic compounds or free radicals) that binds covalently to hepatocytes, leading to liver injury/diseases like acute and chronic hepatitis, cholestasis, steatosis among others. Mitochondrial dysfunction, oxidative stress and lipid peroxidation are some of the mechanisms of liver injury. Furthermore, drug hepatotoxicity results in hepatocellular, gastroenterological, cholestatic as well as immunological disorders. The clinical manifestations of drug toxicity arise from the abnormalities observed in liver’s biochemical and molecular indicators. Our findings, revealed that in the event of liver injury, liver function indices like aspartate and alanine aminotransferases, ALP (alkaline phosphatase) and gamma glutamyl transferase (GGT) activities, intracellular calcium (Ca2+) and lipid peroxidation increases whereas indices of oxidative stress such as glutathione and its allies, catalase and superoxide dismutase activity deplete. At molecular level, the gene expression levels of Bcl-2 mRNA and microRNA genes (miR-122, 192 and 194) reduces while mitochondrial genes (MMP-2 and MMP-9) overexpresses. Since drug abuse is deleterious to human health, therefore, adherence to doctors’ prescription guidelines should be followed.