Study on free radicals and pancreatic fibrosis--pancreatic fibrosis induced by repeated injections of superoxide dismutase inhibitor.
The exact mechanisms of the development of pancreatic fibrosis are still unknown. To clarify the relationship between pancreatic fibrosis and free radicals, the effect of the administration of a superoxide dismutase (SOD) inhibitor, diethyldithiocarbamate (DDC), on pancreatic fibrosis in rats was studied. A single intraperitoneal injection of 500 mg/kg of DDC significantly reduced SOD activity and significantly increased lipid peroxidation products in the pancreas, showing no histologic changes of inflammation or necrosis. Repeated administration of 500 mg/kg DDC, twice a week, caused inter- and intralobular fibrosis with atrophy of acinar cells in the pancreas for at least 2 weeks without fibrosis of the liver and kidney. Administration of allopurinol showed preventive effects against DDC-induced pancreatic fibrosis. In conclusion, repeated administration of DDC, which caused pancreatic fibrosis, is a new experimental model of pancreatic fibrosis from the viewpoint of oxidative stress.
Matsumura
N
N
Second Department of Internal Medicine, Okayama University Medical School, Japan. nytm-m@terra.dti.ne.jp
Ochi
K
K
Ichimura
M
M
Mizushima
T
T
Harada
H
H
Harada
M
M
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001284:Atrophy; D002908:Chronic Disease; D004050:Ditiocarb / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D005609:Free Radicals / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010195:Pancreatitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D005609:Free Radicals; D008054:Lipid Peroxides; D000493:Allopurinol; D004050:Ditiocarb; D013482:Superoxide Dismutase