Yonsei Med J.  2007 Dec;48(6):1028-1034. 10.3349/ymj.2007.48.6.1028.

Ascorbic Acid Alleviates Pancreatic Damage Induced by Dibutyltin Dichloride (DBTC) in Rats

• Lu XL
• Song YH
• Fu YB
• Si JM
• Qian KD

• KMID: 1786220
• DOI: http://doi.org/10.3349/ymj.2007.48.6.1028

Abstract

PURPOSE: Because previous studies have reported depleted antioxidant capacity in patients with chronic pancreatitis (CP), prevention of free radical production has gained importance in antifibrotic treatment strategies for CP. The aim of this study was to investigate the effects of ascorbic acid on oxidative capacity and pancreatic damage in experimental CP. MATERIALS AND METHODS: CP was induced in male Sprague-Dawley rats by infusion of dibutyltin dichloride (DBTC) into the tail vein. Ascorbic acid was given intraperitoneally at a daily dose of 10mg/kg body weight. The treatment groups were as follows: group 1, DBTC plus intraperitoneal physiologic saline; group 2, DBTC plus intraperitoneal ascorbic acid; group 3, solvent plus intraperitoneal physiologic saline; group 4, no operation plus intraperitoneal physiologic saline. Each group contained 15 animals. Treatment was started after CP was established. After 4 weeks of treatment, serum hyaluronic acid and laminin levels were determined by radioimmunoassay, pancreatic tissue oxidative stress was analyzed, and the degree of pancreatic damage was determined. RESULTS: Ascorbic acid treatment markedly increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) concentrations in pancreatic tissue (p < 0.01 for both). Significant serum hyaluronic acid and laminin reductions were observed in group 2 as compared with group 1 (p < 0.05). However, the serum hyaluronic acid and laminin levels remained elevated when compared with those of groups 3 and 4 (p < 0.05). Histopathologic scores were also lower in animals with CP that underwent ascorbic acid-treatment (p < 0.05). CONCLUSION: Ascorbic acid treatment alleviated the degree of oxidative stress and pancreatic damage in rat CP. Antioxidant treatment might be considered a potential option to improve the pathologic process in CP.

Keyword

Ascorbic acid; chronic pancreatitis; antioxidant; dibutyltin dichloride (DBTC)

MeSH Terms

Animals
Antioxidants/pharmacology
Ascorbic Acid/*pharmacology
Hyaluronic Acid/blood
Laminin/blood
Male
Organotin Compounds
Oxidative Stress/drug effects
Pancreas/*drug effects/pathology
Pancreatic Diseases/blood/chemically induced/*prevention & control
Rats
Rats, Sprague-Dawley

Figure

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  Fig. 1 Ascorbic acid treatment reduced serum hyaluronic acid and laminin concentrations (µg/L) in experimental chronic pancreatitis. Serum hyaluronic acid and laminin analysis: group 1 vs group 3, group 1 vs group 4; p < 0.01. Group 2 vs group 1, group 2 vs group 3, group 2 vs group 4; p < 0.05. Group 3 vs group 4; p > 0.05. Group 1, DBTC plus intraperitoneal physiologic saline; group 2, DBTC plus intraperitoneal ascorbic acid; group 3, solvent plus intraperitoneal physiologic saline; group 4, no operation plus intraperitoneal physiologic saline.

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  Fig. 2 Ascorbic acid treatment increased superoxide dismutase (SOD) levels and decreased malondialdehyde (MDA) concentrations in pancreatic tissue in experimental chronic pancreatitis. Pancreatic tissue SOD and MDA analysis: group 1 vs group 2, group 1 vs group 3, group 1 vs group 4; p < 0.01. Group 2 vs group 3, group 2 vs group 4; p < 0.05. Group 3 vs group 4; p > 0.05. SOD, U/g wet weight; MDA, 10-10 mol/g wet weight. Group 1, DBTC plus intraperitoneal physiologic saline; group 2, DBTC plus intraperitoneal ascorbic acid; group 3, solvent plus intraperitoneal physiologic saline; group 4, no operation plus intraperitoneal physiologic saline.

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  Fig. 3 Effect of ascorbic acid on pancreatic pathology in experimental chronic pancreatitis (hematoxylin and eosin staining, original magnification: × 200). Group 1, DBTC plus intraperitoneal physiologic saline; group 2, DBTC plus intraperitoneal ascorbic acid.

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