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.