Research Report
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World J Gastroenterol. Dec 14, 2014; 20(46): 17407-17415
Published online Dec 14, 2014. doi: 10.3748/wjg.v20.i46.17407
Hepatoprotective effect of nitric oxide in experimental model of acute hepatic failure
Marek Saracyn, Marek Brytan, Robert Zdanowski, Tomasz Ząbkowski, Przemysław Dyrla, Janusz Patera, Stanisław Wojtuń, Wojciech Kozłowski, Zofia Wańkowicz
Marek Saracyn, Zofia Wańkowicz, Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, 04-141 Warsaw, Poland
Marek Brytan, Department of Pharmacology and Toxicology, Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland
Robert Zdanowski, Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland
Tomasz Ząbkowski, Department of Urology, Military Institute of Medicine, 04-141 Warsaw, Poland
Przemysław Dyrla, Stanisław Wojtuń, Department of Gastroenterology, Military Institute of Medicine, 04-141 Warsaw, Poland
Janusz Patera, Wojciech Kozłowski, Department of Pathology, Military Institute of Medicine, 04-141 Warsaw, Poland
Author contributions: Saracyn M was the main author, and leader of the research; Saracyn M, Brytan M, Zdanowski R and Dyrla P designed the research; Saracyn M, Brytan M, Zdanowski R, Ząbkowski T and Patera J performed the research; Saracyn M, Brytan M and Dyrla P contributed analytic tools; Saracyn M, Patera J, Wojtuń S and Kozłowski W analyzed the data; Saracyn M, Brytan M, Dyrla P and Wańkowicz Z wrote the paper; Saracyn M, Wojtuń S and Wańkowicz Z revised the paper.
Supported by A grant from the Ministry of Science and Higher Education, No. 216/KBL/12
Correspondence to: Marek Saracyn, MD, PhD, Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, Szaserów St. 128, 04-141 Warsaw, Poland. msaracyn@interia.pl
Telephone: +48-22-6816811 Fax: +48-22-6816811
Received: May 5, 2014
Revised: July 8, 2014
Accepted: September 5, 2014
Published online: December 14, 2014
Processing time: 227 Days and 11.4 Hours
Abstract

AIM: To evaluate the effect of nitric oxide (NO) on the development and degree of liver failure in an animal model of acute hepatic failure (AHF).

METHODS: An experimental rat model of galactosamine-induced AHF was used. An inhibitor of NO synthase, nitroarginine methyl ester, or an NO donor, arginine, were administered at various doses prior to or after the induction of AHF.

RESULTS: All tested groups developed AHF. Following inhibition of the endogenous NO pathway, most liver parameters improved, regardless of the inhibitor dose before the induction of liver damage, and depending on the inhibitor dose after liver damage. Prophylactic administration of the inhibitor was more effective in improving liver function parameters than administration of the inhibitor after liver damage. An attempt to activate the endogenous NO pathway prior to the induction of liver damage did not change the observed liver function parameters. Stimulation of the endogenous NO pathway after liver damage, regardless of the NO donor dose used, improved most liver function parameters.

CONCLUSION: The endogenous NO pathway plays an important role in the development of experimental galactosamine-induced AHF.

Keywords: Nitric oxide; Acute hepatic failure; Nitric oxide synthase; Rat model; Galactosamine

Core tip: We investigated the role of the nitric oxide (NO) pathway in the pathogenesis of acute hepatic failure (AHF). The precise pathomechanism of AHF is poorly understood. In our study, most liver function parameters improved both before and after the induction of liver damage following inhibition of the NO pathway. Prophylactic administration of the inhibitor was more effective in improving liver function parameters. On the other hand, stimulation of the NO pathway after liver damage, regardless of the donor dose used, also improved most liver function parameters. Therefore, the NO pathway significantly influences the development of experimental galactosamine-induced AHF.