THE EFFECTS OF ILOPROST (ZK 36374) AND NORDIHYDROGAUIRETIC ACID ON WARM LIVER ISCHEMIA AND REPERFUSION

Abstract

In this study, the effects of iloprost (ZK 36374) and nordihydrogauiretic acid (NDGA) on warm ischemia and reperfusion injury in rat liver were investigated. The portal and hepatic arterial flow to the left and median lobes of the liver was interrupted selectively for one hour. Rats were given isotonic saline (n: 15, control group), iloprost 25 µg/kg iv (n: 15, ilo group) just before warm ischemia or NDGA 10 µg/kg iv (n: 15, NDGA group) 5 minutes before reperfusion or the same drugs were given together (n:15, ilo+NDGA group). AST, ALT and LDH values were determined prior to ischemia and 6 minutes, 2 hours, 2 days and 7 days after reperfusion. Tissue malonedialdehyde (MDA), gluthathione (GSH), PGE2 and leukotriene C4 levels were determined 6 minutes and 2 days after ischemia/reperfusion injury. Histopathologic examination of the liver was carried out under light microscope. The serum AST, ALT and LDH levels improved significantly in ilo, NDGA and ilo+NDGA groups when compared to the control group (p<0.05). Iloprost and NDGA didn't exert an additive effect. There was a significant decrease (p<0.05) in tissue MDA levels and a significant increase (p<0.05) in tissue GSH levels in the ilo group when compared to control and ilo+NDGA groups. The values did not differ significantly in the ilo+NDGA group when compared to control group. The LTC4/PGE2 ratio was found to be lower in the NDGA and ilo+NDGA groups. In conclusion, iloprost and NDGA were found to be beneficial in preventing the ischemia/reperfusion injury in the rat liver. Iloprost proved to be more protective. The loss of the beneficial effect of iloprost when both drugs were given together was related to either typoxygenase inhibitory effect and / or direct toxic effect of NDGA to rat liver.