Oxidative stress, toxic hepatitis, and antioxidants with particular emphasis on zinc

Hepatic metabolism of biological toxins, industrial poisons, and medicinal agents involves disturbed hepatic cell biochemistry with augmented generation of reactive oxygen species and free radicals and redox imbalance with secondary damage to proteins, nucleic acids, lipids, and carbohydrates. The xenobiotic hepatotoxicity ranging from a subclinical anicteric state to severe necroinflammatory hepatitis (acute, recurrent or chronic) and cirrhosis depends on the nature, dosage, and duration of exposure to the xenobiotic, the antioxidant defence, and concomitant exposure to other diseases or xenobiotics. Experimental and clinical studies suggest that xenobiotic hepatotoxicity with variable depletion of antioxidants can be avoided or ameliorated by administration of an unusually high dosage of zinc or by a combination of antioxidants above normal daily requirements. Therefore reassessment of optimal prophylactic and therapeutic nutritional requirements of antioxidants (particularly zinc) to defend humans against xenobiotic induced oxidative stress is advocated. (C) 2003 Elsevier Inc. All rights reserved.