Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 14, 2006; 12(2): 259-264
Published online Jan 14, 2006. doi: 10.3748/wjg.v12.i2.259
Antioxidative effect of melatonin, ascorbic acid and N-acetylcysteine on caerulein-induced pancreatitis and associated liver injury in rats
Mukaddes Eşrefoğlu, Mehmet Gül, Burhan Ateş, Kadir Batçıoğlu, Mukadder Ayşe Selimoğlu
Mukaddes Eşrefoğlu, Mehmet Gül, Department of Histology and Embryology, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey
Burhan Ateş, Department of Chemistry, Faculty of Science and Art, Inonu University, 44280, Malatya, Turkey
Kadir Batçıoğlu, Department of Biochemistry, Faculty of Pharmacy, Inonu University, 44280, Malatya, Turkey
Mukadder Ayşe Selimoğlu, Department of Pediatric Gastroenterology, Hepatology and Nitrution, Faculty of Medicine, Ataturk University, Erzurum, Turkey
Correspondence to: Mukaddes Eşrefoğlu, InönüÜniversitesi, Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, 44280, Malatya, Turkey. drmukaddes@hotmail.com
Telephone: +90-422-3410660 Fax: +90-422-3410036
Received: May 9, 2005
Revised: May 22, 2005
Accepted: May 24, 2005
Published online: January 14, 2006
Abstract

AIM: To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis and associated liver injury in rats.

METHODS: Thirty-eight female Wistar rats were used. Acute pancreatitis (AP) was induced by two i.p. injections of caerulein at 2-h intervals (at a total dose of 100 µg/kg b.wt). The other two groups received additional melatonin (20 mg/kg b.wt) or an antioxidant mixture containing L(+)-ascorbic acid (14.3 mg/kb.wt.) and N-acetyl cysteine (181 mg/kg b.wt.) i.p. shortly before each injection of caerulein. The rats were sacrificed by decapitation 12 h after the last injection of caerulein. Pancreatic and hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde (MDA) and changes in tissue antioxidant enzyme levels, catalase (CAT) and glutathione peroxidase (GPx). Histopathological examination was performed using scoring systems.

RESULTS: The degree of hepatic cell degeneration, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration showed a significant difference between caerulein and caerulein + melatonin (P  = 0.001), and careulein and caerulein + L(+)-ascorbic acid + N-acetyl cysteine groups (P  = 0.002). The degree of aciner cell degeneration, pancreatic edema, intracellular vacuolization and inflammatory infiltration showed a significant difference between caerulein and caerulein + melatonin (P  = 0.004), and careulein and caerulein + L(+)-ascorbic acid + N-acetyl cysteine groups (P = 0.002). Caerulein-induced pancreatic and liver damage was accompanied with a significant increase in tissue MDA levels (P  = 0.01, P  = 0.003, respectively) whereas a significant decrease in CAT (P  = 0.002, P = 0.003, respectively) and GPx activities (P  = 0.002, P  = 0.03, respectively). Melatonin and L(+)-ascorbic acid + N-acetyl cysteine administration significantly decreased MDA levels in pancreas (P  = 0.03, P  = 0.002, respectively) and liver (P  = 0.007, P  = 0.01, respectively). Administration of these agents increased pancreatic and hepatic CAT and GPx activities. Melatonin significantly increased pancreatic and hepatic CAT (P  = 0.002, P  = 0.001, respectively) and GPx activities (P  = 0.002, P  = 0.001). Additionally, L(+)-ascorbic acid+N-acetyl cysteine significantly increased pancreatic GPx (P  = 0.002) and hepatic CAT and GPx activities (P  = 0.001, P  = 0.007, respectively)

CONCLUSION: Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage. Antioxidant agents such as melatonin and ascorbic acid + N-acetyl cysteine, are capable of limiting pancreatic and hepatic damage produced during AP via restoring tissue antioxidant enzyme activities.

Keywords: Caerulein, Liver, Melatonin, Oxidative stress, Pancreatitis