Effects of ischemia-reperfusion injury on the gene expression of some cytochrome P450 isoforms in the rat liver

    Hepatic ischemia-reperfusion (IR) injury may affect different biological and functional roles of the liver. Liver accounts as an important organ for metabolizing different compounds and drugs in which cytochrome P_450s (CYPs), play an important role. This study aimed to investigate the effects of IR injury on the gene expression of the major CYPs isoforms in the rat liver. Four groups (n=5) of male Sprague-Dawley rats underwent 60 min lobar hepatic ischemia followed by 1, 6, 12 or 24h reperfusion, and a sham-operated group was selected as control. At the end of each reperfusion period, blood samples were taken to evaluate enzyme alterations induced by IR and then animals were euthanatized and tissue samples were taken to study IR-induced changes in gene expression of some CYPs isoforms. Total RNA was isolated from the rat liver tissue and then cDNA was synthesized from an mRNA template. The level of mRNA expression in the liver was analyzed by real-time PCR using specific primers for CYP450 isoforms. The levels of ALT, AST and ALP in the groups subjected to IR was significantly (P<0.05) increased during different times of reperfusion and reached to the peak 6h after the reperfusion. However, the level of CYP1A1, CYP3A1 and CYP2E1 mRNA was significantly (P<0.05) decreased during 6, 12 and 24h of reperfusion. These results showed that IR injury may induce down regulation of the individual CYP₄₅₀ isoforms and these changes may affect CYP-mediated drug metabolizing activities by the liver.