Effects of vitamin C and melatonin on cysteamine-induced duodenal ulcer in a cholestatic rat model: A controlled experimental study

摘要

>Background: Superoxide dismutase (SOD) is one of the defense mechanisms against free radicals. Cysteamine is a cytotoxic agent, acting through generation of reactive oxygen species (ROS) such as hydrogen peroxide, hydroxyl radical, and superoxide, and may decrease defense activity of SOD against ROS and induce duodenal ulcer. Melatonin is a suicidal antioxidant that has a protective effect against ROS and cytoprotective effect through inhibition of the decrease in SOD activity.>Objectives: The primary aim of this study was to assess the effects of pretreatment with vitamin C and melatonin on cysteamine-induced duodenal ulcer. Secondary aims were to compare the ulcerogenic effect of cysteamine and the antiulcer effects of vitamin C and melatonin.>Methods: This study was performed in male Wistar rats (200–250 g) in 3 groups of equal size (n = 24): bile duct ligation-induced cholestasis (test), sham, and control groups. In the test and sham groups, laparotomy was performed under general anesthesia and the common bile duct was identified; in sham rats, the common bile duct was left in situ, but in test rats, the common bile duct was isolated and doubly ligated to induce cholestasis. Animals in each group were also divided into 4 equal subgroups (n = 6). These subgroups were treated with vitamin C plus cysteamine, melatonin plus cysteamine, cysteamine alone, and saline, respectively. All animals were euthanized via overdose of ether anesthesia 24 hours after the last injection of cysteamine or saline, and 0.5 mL of blood was collected from the heart ventricle. The duodenum was cut open, washed with saline, fixed, and prepared for calculation of ulcer index (Szabo method) and histopathologic assessment. SOD activity was measured using a branded enzyme kit.>Results: In all 3 groups, animals treated with cysteamine had significantly increased mean (SE) ulcer index (test, 4.00 [0.10] vs 1.17 [0.30]; sham, 3.83 [0.16] vs 0.50 [0.22]; control, 3.67 [0.21] vs 0 [0]) and decreased SOD activity (test, 146.41 [2.16] vs 299.83 [1.94] U/mL; sham, 154.75 [2.02] vs 303.08 [0.35] U/mL; control, 157.08 [1.67] vs 314.50 [1.14] U/mL) compared with saline-treated rats (all, P < 0.001). In the test rats, ulcer index was significantly increased and SOD activity was significantly decreased compared with the sham and control groups (both, P < 0.001). Pretreatment with vitamin C and melatonin was associated with attenuation of ulcer index and increased SOD activity compared with rats treated with cysteamine alone (P < 0.001). There were no significant differences in ulcer index or SOD activity between groups administered vitamin C or melatonin.>Conclusions: In this experimental study, pretreatment with melatonin or vitamin C in all rats produced significant attenuation of the ulcer index and enhanced SOD activity. Cysteamine-induced duodenal mucosal damage was greater in cholestatic rats compared with sham and control rats.