Involvement of oxygen-derived free radicals in L-arginine-induced acute pancreatitis.
This study was aimed at an assessment of the role of oxygen-derived free radicals in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat, by measuring the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase, and superoxide dismutase (Mn- and Cu,Zn-SOD) in the pancreatic tissue, and evaluating the protective effect of the xanthine oxidase inhibitor allopurinol. Acute pancreatitis was induced in male Wistar rats by injecting 2 x 250 mg/100 g body weight of Arg intraperitoneally in a 1-hr interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. Allopurinol, 100 or 200 mg/kg, was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, and 48 hr following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 hr after the Arg injection (30,800+/-3813 vs 6382+/-184 units/liter in the control) and normalized at 48 hr. The tissue concentration of MDA was significantly elevated at 24 hr and reached the peak value at 48 hr (5.00+/-1.75 vs 0.28+/-0.05 nM/mg protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 hr, and the Cu,Zn-SOD activity was significantly lower at 12 hr after the Arg injection as compared with the controls. Allopurinol treatment markedly reduced the serum amylase elevation (12.631+/-2.257 units/liter at 24 hr) and prevented the increase in tissue MDA concentration (0.55+/-0.09 nM/mg protein at 48 hr). Both doses of allopurinol significantly ameliorated the pancreatic edema, necrosis, and inflammation at 48 hr after Arg administration. Oxygen-derived free radicals are generated at an early stage of Arg-induced acute pancreatitis. Prophylactic allopurinol treatment prevents the generation of reactive oxygen metabolites, reduces the serum amylase concentration, and exerts a beneficial effect on the development of histopathological changes.
First Department of Medicine, Albert Szent-Györgyi Medical University, Szeged, Hungary.
L
L
Czakó
T
T
Takács
I S
IS
Varga
L
L
Tiszlavicz
D Q
DQ
Hai
P
P
Hegyi
B
B
Matkovics
J
J
Lonovics
D000208:Acute Disease; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001120:Arginine; D002374:Catalase / Q000032:analysis; D005609:Free Radicals / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000032:analysis; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000032:analysis; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D005609:Free Radicals; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D000493:Allopurinol; D001120:Arginine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase