Role of nitric oxide and endogenous antioxidants in thyroxine facilitated healing of ischemia-reperfusion induced gastric ulcers

Abstract

Background: Studies have revealed the role of thyroxine during healing of gastric ulcers with information lacking on the mechanism involved hence the focus of this study.Materials and Methods: Adult male Wistar rats (150 – 200g) were randomly divided into 4 groups (n=5 per group): Normal control (NC), Sham ulcerated (SU), Thyroidectomised ulcerated untreated (ThU) and Thyroidectomised ulcerated + Levo-thyroxine (100μg/kg/day) (ThU + T4). Animals were stabilised for 35 days following thyroidectomy and treated accordingly to experimental groupings. Weekly body weight changes were recorded, gastric ulcer was induced by ischemia-reperfusion and gastric acid secretion evaluated. They were sacrificed 1 hour, 3 and 7 days post ulcer induction, blood samples collected for haematological indices through cardiac puncture and their stomachs prepared for gross and microscopic examinations to assess gastric healing. Gastric tissue protein, malondialdehyde (MDA), Superoxide Dismutase (SOD), Catalase (CAT), and Nitric oxide (NO) were assessed as biomarkers of healing. Data were analysed using one way ANOVA and Student’s t test with p< 0.05 considered statistically significant.Results: Thyroxine treated rats showed significant weight loss compared with NC and ThU groups. Percentage healing rate was significantly increased in thyroxine treated group compared with ThU animals by 1 hour (42.45% and -42.81%), days 3 (35.14% and -59.36%), and 7 (64.29% and -115.7%). Hematological indices significantly increased in thyroxine treated group compared with other groups. Thyroxine treatment significantly reduced Neutrophil/Lymphocyte; Platelet/NO as well as lipid peroxidation index in this study. Superoxide dismutase, CAT and NO increased significantly in thyroxine treated rats compared with other groups.Conclusion: Thyroxine treatment facilitates the healing of ischeamic-reperfused gastric ulcers possibly by increasing NO activity which in turn causes increased vasodilatation and enhanced endogenous antioxidants at the ulcer sites.Keywords: Nitric Oxide, Antioxidants, Thyroidectomy, Levo-thyroxine, Ulcer healing.