EFFECTS OF THYROIDECTOMY AND THYROXINE TREATMENT ON GASTRIC ULCER HEALING IN RATS

Abstract

Embryologic and phylogenic relationships have been established between the thyroid gland and the gastrointestinal tract. Although previous studies suggested that thyroxine treatment influences the secretion of gastric acid and ulcerogenesis in man and experimental animals, there is no available information on its role on gastric ulcer healing processes. The effects of thyroidectomy and thyroxine treatment on healing of gastric ulceration were investigated. Two hundred and sixty male albino rats (160 – 200g) were divided into: control, thyroxine treated (100μg/Kg/day, p.o) and thyroidectomised animals with or without thyroxine replacement. Thirty-five days post-treatment, the plasma levels of thyroxine, triiodothyronine and thyroid stimulating hormone were estimated by radioimmunoassay to confirm thyroid states. Experimental ulcers were then induced in the stomach of animals by serosal application of acetic acid (0.5ml, 80%). The following indices of ulcer healing were determined in five rats per group on each of days 3, 7 and 10 post-induction: ulcer area by planimetry, ulcer depth and width by histomorphometry, tissue regeneration by histology. Acid secretion was studied by continuous perfusion method. Lipid peroxidation and white blood cell counts were determined by spectrophotometry and haemocytometry respectively. The DNA damage was studied by electrophoresis and visualised by UV exposure after ethidium bromide staining. Data were analysed using Students t-test at p = 0.05. The rate of ulcer healing was significantly higher in thyroxine-treated (0.8 ± 0.1mm2/day) and lower in thyroidectomised (0.3 ± 0.1mm2/day) rats when compared with control (0.5 ± 0.1mm2/day) by day 10. There were significant reductions in ulcer width and depth in thyroxinetreated animals (69.3 ± 1.5% and 65.7 ± 1.4 % respectively) when compared with control (40.5 ± 2.2% and 53.9 ± 1.6%) and thyroidectomised rats (34.1 ± 0.5% and 35.6 ± 7.5%). Histology revealed gastric ulceration in all groups on day 3, with presence of inflammatory cells at ulcer bed. By day 7, marked reduction in the inflammatory cell and greater fibroblast proliferation were observed in control and thyroxine-treated but not in thyroidectomised animals. On day 10, there was marked epithelial regeneration in thyroxine-treated animals, while thyroidectomised animals had abundant inflammatory cells. Basal and histamine-stimulated gastric acid secretion declined over the healing period at a higher rate in thyroxine-treated rats (77.4 ± 2.6% and 48.3 ± 3.4% respectively) when compared with control (65.0 ± 0.0% and 30.4 ± 1.9%). The reduction in neutrophil-lymphocyte ratio accompanying healing was highest in the thyroxine-treated (65.0 ± 2.5%) and lowest in thyroidectomised rats (20.1± 1.7%) when compared with control (28.3 ± 2.8%). Thyroxine significantly reduced lipid peroxidation from 271.3 ± 9.9nmol/mg protein on day 3 to 120.0 ± 13.9nmol/mg protein on day 10 and suppressed acetic acid induced DNA fragmentation, suggesting its antiapoptotic role during ulcer healing. The deficiencies observed in thyroidectomised animals were restored by therapy with exogenous thyroxine. Thyroidectomy delayed ulcer healing while thyroxine treatment accelerated it. Thyroxine had anti-inflammatory action in the rat stomach, decreased gastric hyperacidity, promoted fibroblast and epithelial cell proliferation.