<small>L</small>-Arginine Protects from Pringle Manoeuvere of Ischemia-Reperfusion Induced Liver Injury

Abstract

During hepatic resection, the risk of severe intra-operative bleeding is a major risk.1) To prevent massive blood loss, continuous or intermittent vascular clamping of the hepatic artery and portal vein ligation is known as "Pringle manoeuvere" is an efficient method to reduce hemorrhage. 2,3) "Pringle manoeuvere" is a technique which leads to ischemic and reperfusion injury. Ischemia and reperfusion results in complex metabolic, 4) immunological 5) and micro vascular 6) changes, which together may contribute to hepatocellular damage and dysfunction. 7) Nitric oxide (NO) is an important modulator of tissue blood flow, arterial pressure, neurotransmission, and immune cell function.8) There is evidence that implicates NO as a modulator of the adhesive interactions among leukocytes, platelets, and endothelial cells 9) and Larginine at a dose level 100 mg/kg/p.o. daily showed significantly protect from alcoholic injury.10) It has been shown that NO-donating compounds provide significant protection against the micro vascular dysfunction that is normally associated with ischemia and reperfusion (I/R).10) L-Arginine is the precursor of NO in vivo and confirmed sustained NO production via L-arginine administration ameliorated effects of intestinal I/R injury.11) However the effect of L-arginine therapy in the view of NO mediated vasodilatation on hepatic ischemia has not yet been completely elucidated. Therefore, this study was designed to investigate how an altered bioavailability of hepatocytes NO produces vasodilatation in hepatic artery supplementation by L-arginine affects the sinusoidal reperfusion and apoptosis under defined surgical techniques i.e. portal triad clamping (Pringle manoeuvere). MATERIALS AND METHODS ChemicalsCollagenase was purchased from Hymedia (Mumbai, India), peroxides-conjugated goat anti-rabbit secondary antibody was purchased from Bio source international (NY, U.S.A.). Alanine transaminase (ALT), aspartate transaminase (AST) kits were procured from Merck India Ltd. (India) and solvents of analytical grade were purchased from Merck (India).Animals Treatment Eighteen Wistar rats were divided into sham-operated control group (I) (nϭ6), ischemia and reperfusion group (II) were given 0.9% saline (5 ml/kg, p.o.) for 7 d (nϭ6), L-arginine pretreated group (100 mg/kg body weight/daily by oral route for 7 d before induced ischemia reperfusion maneuver) (III) (nϭ6). All rats were treated in accordance with the guideline for the Care and Use of Laboratory Animals (NIH Publication No. 86-23, revised 1985) with the permission of institute ethical committee. The hepatic I/R protocol were performed as described earlier. 12)Procurement of Tissue and Blood A portion of the ischemic and non-ischemic liver lobe was fixed in buffered 10% formalin and Karnovsky's solution for histopathology and transmission electron microscopy (TEM) studies. Blood samples were obtained from the right ventricle via a left anterior thoracotomy at the time of sacrifice. The blood from different groups rats were collected in steri...

The influence of short-term l-arginine supplementation on rats’ muscular and hepatic cells in ischemia–reperfusion syndrome

“…In contrast to our results, Chattopadhyay et al [6] demonstrated that pre-treatment with L-arginine significantly decreased serum-ALAT after 1 h ischemia followed by 3 h reperfusion. Histopatology study showed markedly diminished hepatocellular injury in L-arginine pretreated rats during the hepatic I/R, which correlated with decreased plasma ALAT.…”

Effects of L-arginine and L-NAME on ischemia-reperfusion in rat liver

“…Shimamura et al 23 observed a significant increase and maximum of AST levels after 12 hours of reperfusion in a model of hepatic IR, with return to basal level from the 3 rd day of reperfusion. Other authors also evidenced a significant increase in aminotransferases levels after hepatic IR 22,24,25 .…”

Effect of recombinant erythropoietin on ischemia–reperfusion-induced apoptosis in rat liver

“…Hepatic ischemia was created by occluding all structures (hepatic artery, portal vein, and bile duct) leading to the left and median liver lobes (~70% of liver mass) with an atraumatic microvascular clamp for 45 min followed by 2 h reperfusion [5]. The body temperature was monitored and maintained at 37 ± 0.4°C by a heating lamp and warm sterile moistened gauze placed over the laparotomy to avoid dehydration.…”