Effects of curcumin on ethanol-induced hepatocyte necrosis and apoptosis: implication of lipid peroxidation and cytochrome c.
Ethanol-induced hepatocyte necrosis and apoptosis are valid in vitro models to investigate the modulatory effects of hepatoprotective/toxic agents such as curcumin. In this study, suspension and monolayer cultures of isolated rat hepatocytes were used. Levels of trypan blue uptake, reduced glutathione, and lipid peroxidation were quantified. Chromatin condensation, caspase-3 activity, and cytochrome c extramitochondrial translocation were also evaluated. Results revealed that curcumin did not protect against either ethanol-induced necrosis or glutathione depletion. Neither did curcumin reduce caspase-3 activation nor chromatin condensation. In contrast, curcumin induced glutathione depletion, caspase-3 activation, necrosis, and apoptosis. Fortunately, all tested curcumin concentrations (1 microM-10 mM) diminished the ethanol-induced lipid peroxidation. In addition, 1 microM curcumin decreased cytochrome c translocation in hepatocyte monolayers. In conclusion, low concentrations of curcumin may protect hepatocytes by reducing lipid peroxidation and cytochrome c release. Conversely, higher concentrations provoke glutathione depletion, caspase-3 activation, and hepatocytotoxicity.
Ghoneim
Asser I
AI
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abbassia, 11566, Cairo, Egypt. asser@asu-pharmacy.edu.eg
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D000431:Ethanol / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008297:Male; D009336:Necrosis; D021381:Protein Transport; D051381:Rats
D000975:Antioxidants; D000431:Ethanol; D045304:Cytochromes c; D053148:Caspase 3; D005978:Glutathione; D003474:Curcumin