Korean J Physiol Pharmacol.
1998 Oct;2(5):629-635.
Effects of small molecular antioxidants on cerulein-induced acute pancreatitis in rat
- Affiliations
-
- 1Department of Pharmacology, Yonsei University College of Medicine, Seoul 120-752, Korea.
Abstract
-
It has been suggested that oxygen free radicals are involved in the
initiation process of acute pancreatitis, although its pathogenesis is
not clear. This study evaluates the roles of oxygen radicals and the
effects of small molecular antioxidants (rebamipide, N-acetyl-cysteine,
allopurinol, beta-carotene) on the development of cerulein-induced
acute pancreatitis. Acute edematous pancreatitis was induced by the
intravenous infusion of cerulein at supramaximal dose of 10 mug/kg/hour
for 3.5 hours. The effects of antioxidants, rebamipide (100 mg/kg,
i.p.), N-acetyl-cysteine (200 mg/kg, i.v.), allopurinol (20
mg/kg/hour), beta-carotene (50 mg/kg, i.p.), were examined. Cerulein
administration resulted in a significant increase in serum amylase
activity and pancreatic malondialdehyde (MDA), but not glutathione
peroxidase (GSHpx). The glutathione (GSH) content in pancreatic tissue
decreased dramatically. Pretreatment of N-acetyl-cysteine significantly
decreased the cerulein-induced hyperamylasemia and maintained GSH
content in pancreas, but MDA was slightly decreased. In addition,
N-acetyl-cysteine ameliorated histological damage. Allopurinol and
beta-carotene attenuated cerulein-induced hyperamylasemia, but
histologically there was no difference from control. These results
indicate that oxygen free radicals play an important role in the
initiation of experimental acute pancreatitis. N-acetyl-cysteine is an
effective antioxidant that ameliorates the cerulein-induced acute
pancreatitis, and the possible therapeutic application of antioxidants
against acute pancreatitis needs a further evaluation.