EFFECTS OF ISCHEMIA-REPERFUSION ON INDIVIDUAL CYTOCHROME-P450 ISOFORMS IN THE RAT-KIDNEY

Ischemia-reperfusion of organs such as the kidney produces reactive ox ygen and free radical species in tissues and leads to injury of intrac ellular molecules critical to cell homeostasis. Ischemia-reperfusion a ffects the NADPH-dependent monooxygenase system including P450 system, which is also a source of reactive oxygen species. In this study, the effects of ischemia-reperfusion on monooxygenase activity and levels of individual P450 isoforms including CYP2C23, 4A2, and 4A8 in the rat kidney were investigated. Ischemia of the rat kidney for 30 min had l ittle effect on lauric acid hydroxylation activity and levels of P450 isoforms but ischemia for 60 min significantly decreased lauric acid w and (omega-1)-hydroxylation activities and also decreased the levels o f CYP2C23, 4A2, and 4A8. Reperfusion for 60 min after 30-min ischemia decreased the levels of CYP2C23 and 4A2 in the rat kidney although 30- min ischemia did not. Reperfusion for 240 min after 30-min or 60-min i schemia recovered the decreased levels of lauric acid hydroxylation ac tivity and the levels of CYP2C23 and 4A2. Changes in the levels of mon ooxygenase activity and the levels of P450 isoforms in kidneys by isch emia-reperfusion are faster than those in the liver; it takes several hours for ischemia-reperfusion to affect the levels of monooxygenase a ctivity and the levels of P450 in the rat liver. Our findings suggest that damage of P450 isoforms in the kidney by ischemia-reperfusion occ urs by a mechanism different from that in the liver and that active ox ygen or free radical species directly attack proteins.