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

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 +/- 6.8 mu kat/L vs 22 +/- 2.6 mu kat/L, P = 0.022). Similarly, alanine aminotransferase (ALT) was also higher in the I/R group than in the nitrite group (34 +/- 6 mu kat vs 14 +/- 1.5 mu kat, P = 0.0045). The NOx in MD was significantly higher in the nitrite group than in the I/R group (10.1 +/- 2.9 mu mol/L vs 3.2 +/- 0.9 mu mol/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 mu mol/L vs 9.2 +/- 1.1 mu mol/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 mu mol/L vs 367 +/- 31 mu mol/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. CONCLUSION: Nitrite administered before liver ischemia in the rat liver reduces anaerobic metabolism and cell necrosis, which could be important in the clinical setting.