[Mechanisms of hepatotoxicity].
Liver disease following the use of hypolipidemic drugs has been reported as a cellular damage (increases in AST or ALT enzymes) without cholestatic alterations (bilirubin and or alkaline phosphatase increases). Six mechanisms were proposed for hepatotoxicity: 1. High energy reactions on P450 cytochrome impairing calcium homeostasis with rupture of intracellular fibrils and hepatocyte lysis. 2. Impairment of transporter proteins related to the bile acids flux (mechanism proposed for fibrate liver toxicity). 3. Immune reactions due to the formation of metabolites linked to enzymes following liver metabolism of hypolipidemic drugs. 4. Hepatotoxicity by T cells with additional inflammation mediated by neutrophils. 5. Apoptosis mediated by TNF and Fas (immune mediated). 6. Oxidative stress due to damage of intracellular organelles. In addition, advanced age, alcohol in excess, high doses of hypolipidemic drugs, interaction with other drugs, and previous active liver disease might increase liver toxicity.
Bertolami
Marcelo Chiara
MC
Instituto Dante Pazzanese de Cardiologia, Secretaria de Estado da Saúde de São Paulo.
D056486:Chemical and Drug Induced Liver Injury; D002994:Clofibrate / Q000009:adverse effects / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000009:adverse effects* / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism; D009525:Niacin / Q000009:adverse effects / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D009525:Niacin; D002994:Clofibrate