Metabolic Activation of Drugs and Other Xenobiotics Hepatocellular Ca【Young Scholars Dissertation Awards Series】

The metabolic activation of many drugs and xenobiotics in vivo is effected through the large family of cytochrome P450s enzymes that catalyse a diverse spectrum of reactions including the metabolism of both endogenous and exogenous compounds. There is considerable evidence suggesting that changes in P450 activities can affect the in vivo toxicity of drugs in both animals and humans. Oxidative metabolism by cytochrome P450 enzymes has been implicated in the pathogenesis of cancer, through the formation of toxic intermediates and carcinogenic metabolites are formed from drugs and xenobiotics. A marked overall increase in the metabolic activation of the commonly used analgesic agent, paracetamol, was found in patients with hepatocellular carcinoma, as indicated by a much higher percentage recovery of the oxidative metabolites cysteine and mercapturate conjugates, compared to healthy controls and patients with chronic hepatitis B infection. It was through that metabolic activation of some drugs and xenobiotics through the actions of specific cytochrome P450s may be enhanced in patients with hepatocellular carcinoma.