Protective effect of L-arginine against necrosis and apoptosis induced by experimental ischemic and reperfusion in rat liver.
OBJECTIVE
To study the effect of L-arginine on apoptosis and necrosis induced by 1-h ischemia followed by 3-h reperfusion.


METHODS
Adult Wistar rats underwent 60 min of partial liver ischemia followed by 3-h reperfusion. Eighteen Wistar rats were divided into sham-operated control group (I) (n = 6), ischemia and reperfusion (I/R) group (0.9 % saline (5 mL/kg, orally) for 7 days) (II) (n = 6), and L-arginine-treated group (10 mg/kg body weight daily orally for 7 days before inducing ischemia-reperfusion maneuver) (III) (n = 6). Apoptotic and necrotic hepatocytes, nitric oxide levels in hepatocytes, Bcl-2 mRNA, and Bcl-2 protein were measured. Liver injury was assessed by plasma alanine transaminases (ALT), aspartate transaminases (AST), liver histopathology, and electron microscopy.


RESULTS
An ischemic and reperfusion hepatocellular injury occurred as was indicated by increased serum ALT, AST, histopathology, and electron microscopy. Apoptosis and necrosis associated marker gene Bcl-2 mRNA and protein expression were decreased in I/R group. Pretreatment with L-arginine significantly decreased serum ALT and AST level and apoptotic and necrotic cells after 1 h ischemia followed by 3 h of reperfusion. Nitric oxide production in hepatocytes was increased twofold by L-arginine treatment when compared with I/R group. Histopathology and transmission electron microscopy (TEM) studies showed markedly diminished hepatocellular injury in L-arginine-pretreated rats during the hepatic I/R.


CONCLUSIONS
Thus, it may be concluded that L-arginine afforded significant protection from necrosis and apoptosis in I/R injury by upregulated Bcl-2 gene and nitric oxide production.
Chattopadhyay
Pronobesh
P
Cellular and Microbiology Laboratory, College of Pharmacy, IFTM, Lodhipur Rajput, Moradabad - 244 001, UP, India. chatto_pronobesh@rediffmail.com
Shukla
Gunjan
G
Wahi
Arun Kumar
AK
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001120:Arginine / Q000494:pharmacology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D019254:Genes, bcl-2 / Q000235:genetics; D007511:Ischemia / Q000473:pathology / Q000517:prevention & control*; D008099:Liver / Q000098:blood supply* / Q000648:ultrastructure; D008107:Liver Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D046529:Microscopy, Electron, Transmission; D009336:Necrosis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D012333:RNA, Messenger; D001120:Arginine