Biochimie & Biochimie Analytique

Abstrait

Drug Metabolism and Oxidative Stress: Cellular Mechanism and New Therapeutic Insights

Sharmistha Banerjee, Jyotirmoy Ghosh and Parames C Sil

Oxidative stress, generated during drug metabolism, acts as a source of origin and progression of many dreadful diseases. Reactive metabolites formed during this process cause oxidative stress and can impair the function of drugmetabolizing enzymes leading to toxicity. It is, therefore, important to investigate the mechanism of drug-induced toxicity and to find a remedy so that cellular toxicity can be minimized. This review highlights the mechanism of reactive oxygen species generation during cytochrome P450 mediated metabolism of various drugs and endogenous molecules, cytochrome mediated metabolism of arachidonic acid and the role of its metabolite, 20-Hydroxy-5,8,11,14- eicosatetraenoic acid in cardiovascular diseases. This review aims to provide updated knowledge on the mechanism of reactive oxygen species generation during drug metabolism, association of drug metabolizing enzyme in diseases and the role of antioxidant therapy that helps to minimize cellular toxicity. The most significant challenges in drug discovery are the unpredictable nature of drug toxicity due to the oxidative stress in drug metabolism. These difficulties can be overcome by inhibiting toxic metabolites formation or by the modification of the structure of the original compounds for the amelioration of toxicity of the toxic metabolites. Another aspect of reducing drug toxicity is the inhibition of the drug metabolizing enzymes.