L-ARGININE, BUT NOT L-NAME PROTECTS AGAINST LIVER INJURY INDUCED BY EXPERIMENTAL ISCHEMIA-REPERFUSION

  • O. M. Oleshchuk Horbachevsky Ternopil State Medical University
  • K. A. Posokhova
  • A. Ye. Mudra

Abstract

Background. Hepatic ischemia-reperfusion (I/R) injury occurs upon restoration of hepatic blood flow after a period of ischemia.
Objective. The study establishes that stimulation or blockade of nitric oxide synthesis has a protective effect during ischemia-reperfusion.
Methods. Male albino rats which were divided into four equal groups: sham-operated control, ischemia and reperfusion group (0.9 % saline i.p.) for 3 days, group pre-treated with L-arginine (25 mg/kg i.p.), group pre-treated with L-NAME (10 mg/kg i.p.) for 3 days before ischemia-reperfusion maneuver. Complete ischemia of the median and left hepatic lobes was induced by clamping the left branches of the portal vein and the hepatic artery for 45 min. Rats were sacrificed after 3-h reperfusion. Nitric oxide synthase 3 (endothelial) and nitric oxide synthase 2 (inducible) expression, nitric oxide stabile metabolites (NO2, NO3) content, AST and ALT activities were determined. Histological examination of liver tissue was performed.
Conclusions. Relative NO deficiency, due to eNOS inhibition, is central in the pathogenesis of hepatic ischemia reperfusion injury. Replacing NO content with either precursors or via donor drugs represents novel methods in ameliorating ischemia-reperfusion injury.

KEY WORDS: hepatic ischemia-reperfusion, nitric oxide, NOS isoforms, L-arginine, L-NAME

Author Biography

O. M. Oleshchuk, Horbachevsky Ternopil State Medical University
Pharmacology and Clinical Pharmacology Department

References

Selzner N, Rudiger H, Graf R, Clavien P. Pro¬tective strategies against ischemic injury of the liver. Gastroenterol 2003; 125: 917-936.

Bahde H, Spiegel HU. Hepatic ischemia-reper- fusion injury from bench to bedside. Bri J Surg 2010; 97: 1461-1475.

Ohmori H, Dhar D, Nakashima Y et al. Beneficial effects of FK409, a novel nitric oxide donor on reperfusion injury of rat liver. Transplantation 1998; 66: 579-585.

Shah V, Kamath SP. Nitric oxide in liver transplantation: pathobiology and clinical implication. Liver Transplantation 2003; 1(9): 1-11.

Lin HI, Wang D, Leu F-J. et al. Ischemia and reperfusion of liver induces eNOS and iNOS expression: effects of NO donor and NOS inhibitor. Chin J Physiol 2004: 47(3): 121-127.

Oleshchuk OM. Experimental study of nitric oxide precursors in hepatic ischemia-reperfusion. Hospital surgery 2012; 4(60): 42-47. (in Ukrainian)

Kiselyk IO, Lutsyk MD, ShevchenkoLYu. Features determination of nitrate and nitrite in the blood of patients with viral hepatitis and jaundice of different etiology. Lab diagnostyka 2001; 3: 43-45. (in Ukrainian)

Phillips L, Lopez-Neblina F, Toledo-Pereyra LH. Nitric oxide mechanism of protection in ischemia and reperfusion injury J Invest Sur 2009; 22: 46-55.

Hines IN, Kawachi S, Harada H et al. Role of nitric oxide in liver ischemia and reperfusion injury. Mol Cell Biochem 2002; 234-235: 229-237.

Chattopadhyay P, Shukla G, Wahi AK. Protective effect of L-arginine against necrosis and apoptosis induced by experimental ischemic and reperfusion in rat liver. Saudi J Gastroenterol 2009; 15 (3): 156-162.

Chander V, Chopra K. Renal protective effect of molsidomine and L-arginine in ischemia-reperfusion induced injury in rats. J Surg Res 2005; 128: 132-139.

Wang LM, Tian XF, Song QY et al. Expression and role of inducible nitric oxide synthase in ischemia- reperfusion liver in rats. Hepatobiliary Pancreat Dis Int 2003; 2: 252-258.

Published
2014-12-25
How to Cite
Oleshchuk, O., Posokhova, K., & Mudra, A. (2014). L-ARGININE, BUT NOT L-NAME PROTECTS AGAINST LIVER INJURY INDUCED BY EXPERIMENTAL ISCHEMIA-REPERFUSION. International Journal of Medicine and Medical Research, 1(1). https://doi.org/10.11603/ijmmr.2413-6077.2015.1.2820
Section
Biomedical Sciences