MANIFESTATIONS OF CHEMICALLY-INDUCED LIVER-DAMAGE

Possible liver damage induced by chemicals or drugs must be detected e arly during drug development or industrial exposure, although damage i s still difficult to predict, especially when immunotoxicity is involv ed. Liver toxicity may result from cytolysis, steatosis, cholestasis, phospholipidosis, or vascular lesions, most the outcome of a disadvant ageous balance between chemicals or metabolites vs protective mechanis ms, resulting from chemical dosage, genetic factors, or the immunoalle rgic status of the patient. Drug metabolism, lipid peroxidation, and t hiol oxidation are frequently involved in liver toxicities. Classical guidelines in toxicology propose many methods for liver toxicity asses sment: histology; chemical changes in hepatic tissue (lipids, glutathi one, enzymes); physiological changes in biosynthesis (proteins, glycop roteins); excretion function (fructose); drug metabolism; and concentr ations of related enzymes (alanine aminotransferase, aspartate aminotr ansferase, alkaline phosphatase, and gamma-glutamyltransferase) in blo od. In vitro studies in human or animal hepatocytes or tumor-derived c ell lines are useful in detecting hepatocellular lesions by cell viabi lity, glutathione concentration, amount of lactate dehydrogenase relea sed, cellular ATP, morphology (blebs), and drug metabolism.