Protective effects of L-arginine on reperfusion injury after pancreaticoduodenal transplantation in rats.
BACKGROUND
Post-transplantation pancreatitis and graft thrombosis are two major complications of pancreas transplantation that contribute to morbidity, mortality, and graft loss. Nitric oxide(NO) is a potent vasodilator agent formed when L-arginine (L-Arg) is converted to L-citrulline by the action of NO synthase (NOS), and plays a major role in microcirculatory changes. We therefore investigated the effect of L-Arg on reperfusion injury following pancreaticoduodenal transplantation in rats.


METHODS
The homologous male Wistar rat model of heterotopic total pancreaticoduodenal transplantation was used. The L-Arg-treated rats received the intravenous injection of L-Arg 5 minutes before and after reperfusion at a dose of 200 mg/kg while the N-Nitro-L-arginine methyl ester (L-NAME)-treated rats at a dose of 10 mg/kg. The amount of NO in the pancreas graft was measured. Serum concentration of cytokine-induced neutrophil chemoattractant (CINC) was determined by enzyme-linked immunosorbant assay, the expression of CINC mRNA was detected by Northern blot assay in the pancreas graft, and the activity of myeloperoxidase (MPO) was measured. Histological examination was performed.


RESULTS
The amount of NO was higher in the L-Arg group than in the control group, while it was lower in the L-NAME group than in the control group (P<0.05). The peak of serum CINC concentration occurred 3 hours after reperfusion with the difference among the groups being significant. The expression peak of CINC mRNA in the pancreas graft occurred 3 hours after reperfusion. The expression level in the L-Arg group (7.66+/-1.53 microg/L) was lower than in the control group (26.31+/-2.01 microg/L), while in the L-NAME group (34.18+/-3.12 microg/L) it was higher than that in the control group (P<0.05). The activity of MPO in the L-Arg group was obviously decreased as compared with in the other groups. The pancreas inflammation was ameliorated when L-Arg was administered, whereas the pancreas damage was aggravated when L-NAME was administered.


CONCLUSIONS
L-Arg can increase the amount of NO and inhibit the elevation of CINC, the CINC mRNA expression and early neutrophil accumulation in the pancreas. NO has protective effects on ischemia/reperfusion injury in pancreaticoduodenal transplantation.
Yuan
Chun-Hui
CH
Department of Organ Transplantation, First Affiliated Hospital of China Medical University, Shenyang 110001, China. ychdoctor@hotmail.com
Liu
Yong-Feng
YF
Cheng
Ying
Y
Zhao
Ning
N
Li
Gui-Chen
GC
Liang
Jing
J
He
San-Guang
SG
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D004386:Duodenum / Q000637:transplantation*; D006085:Graft Survival / Q000187:drug effects; D017665:Hydroxyl Radical / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D016035:Pancreas Transplantation; D030421:Peroxynitrous Acid / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism
D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D001120:Arginine