Limitations of exogenous L-arginine in exerting a cytoprotective effect on hepatic ischemia/reperfusion injury.
To test whether or not the L-arginine/nitric oxide (NO) pathway induces a protective effect, we investigated the effect of exogenous L-arginine on hepatic ischemia/reperfusion (I/R) injury, using ex vivo perfusion of the isolated rat liver. The rat liver was removed and preserved in cold saline for 60 min, followed by 120 min of reperfusion with oxygenated perfusate at 37 degrees C. Either 600 mg/kg of L-arginine (groups 1 and 4), D-arginine (group 2), N(G)-nitro-L-arginine methyl ester (L-NAME) (group 3), or saline (group 5) were administered through the portal vein starting from 5 min before reperfusion to 5 min after reperfusion. In group 4, 600 mg/kg of L-NAME was preadministered at 10 min prior to the administration of L-arginine. The intrahepatic nitric oxide (NO) levels showed only a temporal elevation (227% +/- 70% of the pre-reperfusion levels at 5 min) after reperfusion in group 1. Pretreatment with L-NAME suppressed the elevation of the NO levels immediately after reperfusion in group 4. The lactate dehydrogenase release to the effluent perfusate significantly decreased and the histological findings showed that the sinusoidal damage observed after reperfusion was mitigated in group 1 more than in the other groups. These results thus suggest that exogenous L-arginine produced a relatively small amount of NO and therefore resulted in a slight decrease of hepatic I/R injury.
Higa
T
T
First Department of Surgery, University of the Ryukyus, School of Medicine, Okinawa, Japan.
Shiraishi
M
M
Mamadi
T
T
Taira
K
K
Oshiro
T
T
Nozato
E
E
Nagahama
M
M
Muto
Y
Y
D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
D009569:Nitric Oxide; D001120:Arginine; D007770:L-Lactate Dehydrogenase