Protective effect of inducible nitric oxide synthase inhibitor on pancreas transplantation in rats.
OBJECTIVE
To investigate the effect of inducible nitric oxide synthase inhibitor, aminoguanidine, on pancreas transplantation in rats.


METHODS
A model of pancreas transplantation was established in rats. Streptozotocin-induced diabetic male Wistar rats were randomly assigned to sham-operation control group (n = 6), transplant control group (n = 6), and aminoguanidine (AG) treatment group (n = 18). In the AG group, aminoguanidine was added to intravascular infusion as the onset of reperfusion at the dose of 60 mg/kg, 80 mg/kg, 100 mg/kg body weight, respectively. Serum nitric oxide (NO) level, blood sugar and amylase activity were detected. Nitric oxide synthase (NOS) test kit was used to detect the pancreas cNOS and inducible NOS (iNOS) activity. Pancreas sections stained with HE and immunohistochemistry were evaluated under a light microscope.


RESULTS
As compared with the transplant control group, the serum NO level and amylase activity decreased obviously and the evidence for pancreas injury was much less in the AG group. The AG (80 mg/kg body weight) group showed the most significant difference in NO and amylase (NO: 66.0 +/- 16.6 vs 192.3 +/- 60.0, P < 0.01 and amylase: 1426 +/- 177 vs 4477 +/- 630, P < 0.01). The expression and activity of tissue iNOS, and blood sugar in the AG (80 mg/kg body weight) group were much lower than those in the transplant control group (iNOS: 2.01 +/- 0.23 vs 26.59 +/- 5.78, P < 0.01 and blood sugar: 14.2 +/- 0.9 vs 16.8 +/- 1.1, P < 0.01).


CONCLUSIONS
Selective iNOS inhibitor, aminoguanidine as a free radical, has a protective effect on pancreas transplantation in rats by inhibiting NO and reducing its toxicity.
Li
Bai-Feng
BF
Department of Surgery and Organ Transplant Unit, The First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China.
Liu
Yong-Feng
YF
Cheng
Ying
Y
Zhang
Ke-Zhong
KZ
Li
Tie-Min
TM
Zhao
Ning
N
D000681:Amylases / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D016035:Pancreas Transplantation / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D006146:Guanidines; D007527:Isoenzymes; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D000681:Amylases; C004479:pimagedine