Melatonin-induced gene expression changes and its preventive effects on adriamycin-induced lipid peroxidation in rat liver.

Adriamycin (ADR) provokes lipid peroxidation process, while melatonin (MEL) is a free radical scavenger that has been found to protect against lipid peroxidation in vitro and in many experimental models. In the present study, the effects of ADR and the combination of ADR and MEL were analyzed on the modulation of fatty acid composition, lipid peroxidation and gene expression in rat liver. Sixty genes were selected for the study of relative gene expression changes in the liver. ADR treatment decreased the polyunsaturated fatty acids C22:6 n-3 and C20:4 n-6 in rat liver mitochondria. When the treatment of ADR was followed by MEL, decrease in these fatty acids could not be detected. A significant increase in lipid peroxidation was observed after administration of ADR, which was restored to control values by post-treatment with MEL. Gene expression profiles of ADR- versus ADR+MEL-treated rat livers indicated that both treatments induced significant changes. Quantitative real-time polymerase chain reaction analysis of 60 genes involved in oxidative stress revealed that cyp1b1, which is involved in electron transport, cyclin-dependent kinase inhibitor 1a that possesses cyclin-dependent protein kinase inhibitor activity, was induced at a more pronounced level in the ADR+MEL-treated samples than in the ADR-treated ones. Several genes having roles in heat-shock response were downregulated in MEL-treated animals, such as hsp40, hsp70 and hsp90 proteins reflecting the reduced oxidative stress in these animals. Global gene expression analysis will highlight the gene expression changes accompanying oxidative damage and its prevention in more details.