Protective mechanism of L-arginine against liver ischemic-reperfusion injury in rats.
OBJECTIVE
To investigate the protective effect of L-arginine (L-arg) against liver ischemic-reperfusion (I/R) injury in rat model and its possible mechanism.


METHODS
Male Sprague-Dawley rats were randomized into sham group: hepatoduodenal ligament mobilized, but not clamped; control group: hepatic ischemia only; Arg group: 5 minutes before hepatic ischemia, L-arg (200 mg/kg) injected via the dorsal penis vein; Arg+L group: 10 and 5 minutes before hepatic ischemia, L-NAME (30 mg/kg) and L-arg (200 mg/kg) injected via the dorsal penis vein, respectively; and Fmk group: 5 minutes before hepatic ischemia, ZVAD-fmk (15 mg/kg) injected via the dorsal penis vein. The liver was subjected to ischemia for 40 minutes by Pringle's maneuver, and reperfusion was initiated by removing clamp. The 7-day survival rate, alanine transaminase (ALT) level, caspase-3 activity and apoptotic hepatocyte count were compared among these groups.


RESULTS
After 40 minutes of ischemia and 6 hours of reperfusion, the 7-day survival rate of the Arg group was significantly higher than that of the control and Arg+L groups (P<0.05). The ALT level, caspase-3 activity and apoptotic hepatocyte count in the Arg group were decreased significantly than those in the control and Arg+L groups (P<0.01). The caspase-3 activity and apoptotic hepatocyte count in the Arg group were slightly higher than those in the sham and Fmk groups, but there was no statistical significance.


CONCLUSIONS
L-arg could ameliorate liver I/R injury and the possible protective mechanism is inhibition of hepatocyte apoptosis via inhibition of caspase-3 activity by nitric oxide synthesis.
Li
Shao-Qiang
SQ
Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China. lesq@163.net
Liang
Li-Jian
LJ
D000410:Alanine Transaminase / Q000032:analysis / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001120:Arginine / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008099:Liver / Q000098:blood supply*; D008111:Liver Function Tests; D008297:Male; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D015427:Reperfusion Injury / Q000517:prevention & control*; D015996:Survival Rate
D001120:Arginine; D000410:Alanine Transaminase; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases