AIM:To investigate whether nitrite administered prior to ischemia/reperfusion(I/R)reduces liver injury.METHODS:Thirty-six male Sprague-Dawley rats were randomized to 3 groups,including sham operated(n=8),45-min segmental ischemia of the left liver lobe(IR,n=14)and ischemia/reperfusion(I/R)preceded by the administration of 480 nmol of nitrite(n=14).Serum transaminases were measured after 4 h of reperfusion.Liver microdialysate(MD)was sampled in 30-min intervals and analyzed for glucose,lactate,pyruvate and glycerol as well as the total nitrite and nitrate(NOx).The NOx was measured in serum.RESULTS:Aspartate aminotransferase(AST)at the end of reperfusion was higher in the IR group than in the nitrite group(40±6.8μkat/L vs 22±2.6μkat/L,P=0.022).Similarly,alanine aminotransferase(ALT)was also higher in the I/R group than in the nitrite group(34±6μkat vs 14±1.5μkat,P=0.0045).The NOx in MD was significantly higher in the nitrite group than in the I/R group(10.1±2.9μmol/L vs 3.2±0.9μmol/L,P=0.031)after the administration of nitrite.During ischemia,the levels decreased in both groups and then increased again during reperfusion.At the end of reperfusion,there was a tendency towards a higher NOx in the I/R group than in the nitrite group(11.6±0.7μmol/L vs 9.2±1.1μmol/L,P=0.067).Lactate in MD was significantly higher in the IR group than in the nitrite group(3.37±0.18 mmol/L vs 2.8±0.12 mmol/L,P=0.01)during ischemia and the first 30 min of reperfusion.During the same period,glycerol was also higher in the IRI group than in the nitrite group(464±38μmol/L vs 367±31μmol/L,P=0.049).With respect to histology,there were more signs of tissue damage in the I/R group than in the nitrite group,and29%of the animals in the I/R group exhibited necrosis compared with none in the nitrite group.Inducible nitric oxide synthase transcription increased between early ischemia(t=15)and the end of reperfusion in both groups.CONCLUSION:Nitrite administered before liver ischemia in the rat liver reduces anaerobic metabolism and cell necrosis,which could be important in the clinical setting.
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