Nitrite, a novel method to decrease ischemia/reperfusion injury in the rat liver.

Abstract

To investigate whether nitrite administered prior to ischemia/reperfusion (I/R) reduces liver injury. 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. Aspartate aminotransferase (AST) at the end of reperfusion was higher in the IR group than in the nitrite group (40 ± 6.8 μkat/L vs 22 ± 2.6 μkat/L, P = 0.022). Similarly, alanine aminotransferase (ALT) was also higher in the I/R group than in the nitrite group (34 ± 6 μkat vs 14 ± 1.5 μkat, P = 0.0045). The NOx in MD was significantly higher in the nitrite group than in the I/R group (10.1 ± 2.9 μmol/L vs 3.2 ± 0.9 μmol/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 ± 0.7 μmol/L vs 9.2 ± 1.1 μmol/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 ± 38 μmol/L vs 367 ± 31 μmol/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, and 29% 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. Nitrite administered before liver ischemia in the rat liver reduces anaerobic metabolism and cell necrosis, which could be important in the clinical setting.