Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2015; 21(6): 1775-1783
Published online Feb 14, 2015. doi: 10.3748/wjg.v21.i6.1775
Nitrite, a novel method to decrease ischemia/reperfusion injury in the rat liver
Per Sandström, Tommy Sundqvist, Hans Olsson, Linda Bojmar, Bergthor Björnsson
Bergthor Björnsson, Per Sandström, Department of Surgery, County Council of Östergötland, 581 85 Linköping, Sweden
Bergthor Björnsson, Linda Bojmar, Tommy Sundqvist, Per Sandström, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, 581 85 Linköping, Sweden
Hans Olsson, Department of Pathology, County Council of Östergötland, 581 85 Linköping, Sweden
Author contributions: Björnsson B, Sundqvist T and Sandström P designed the research; Björnsson B and Bojmar L performed the research; Björnsson B, Bojmar L, Olsson H, Sundqvist T and Sandström P analyzed the data; and Björnsson B, Bojmar L, Olsson H, Sundqvist T and Sandström P wrote the paper.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Bergthor Björnsson, MD, Department of Surgery, County Council of Östergötland, Garnisonsvägen, 581 85 Linköping, Sweden. bergthor.bjornsson@lio.se
Telephone: +46-10-1030000 Fax: +46-10-1033570
Received: June 9, 2014
Peer-review started: June 10, 2014
First decision: August 6, 2014
Revised: August 24, 2014
Accepted: October 15, 2014
Article in press: October 15, 2014
Published online: February 14, 2015
Processing time: 247 Days and 14.6 Hours
Abstract

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 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.

CONCLUSION: Nitrite administered before liver ischemia in the rat liver reduces anaerobic metabolism and cell necrosis, which could be important in the clinical setting.

Keywords: Ischemia-reperfusion injury; Nitrite; Liver ischemia; Liver surgery; Microdialysis; Nitric oxide; Inducible nitric oxide synthase

Core tip: Nitric oxide has an important protective effect against liver ischemia/reperfusion injury (IRI), although large levels of the substance may increase IRI. The total levels of nitrite and nitrate decrease in the liver tissue during ischemia. Because nitrite can be reduced to nitric oxide (NO) in an acidic environment, this decrease may be due to NO formation. In this study, the administration of nitrite before liver ischemia/reperfusion reduced the IRI per evaluation with transaminases, liver microdialysis and histology.