REVERSAL OF SODIUM ARSENITE-INDUCED DELAY IN GASTRIC ULCER HEALING IN RATS BY KOLAVIRON, VITAMIN E AND ZINC

Abstract

Arsenic acid is a major contaminant of various water sources used for human consumption and industrial activities in most developing countries. It has been reported to cause degenerative inflammation and oxidative damage in many tissues. However, there is a paucity of information on its effect on various gastrointestinal tract conditions of exposed individuals. A mechanistic study in rats on the ameliorative activities of antioxidants (kolaviron, zinc, and vitamin E) on the effects of Sodium Arsenite (SA) exposure during acetic acid - induced gastric ulcer healing was undertaken. Wistar rats (n=125,150-200g), randomly divided into five groups were treated for two weeks as follows: control (distilled water), SA (5mg/kg, p.o), SA+ kolaviron (100 mg/kg, p.o), SA+ vitamin E (100mg/kg, p.o), SA + zinc sulphate (20mg/kg p.o). Kolaviron was obtained from Garcinia Kola using soxhlet extraction process. Gastric ulceration was induced by administration of acetic acid (0.06ml, 40% v/v). Indices of ulcer healing determined on days 3, 7, 14 and 21 post induction were ulcer score and area using planimetry, total gastric acidity by titration, and neutrophil/inflammatory cell infiltration using histomorphometry. Blood cells were quantified using haemocytometry and activities of Superoxide Dismutase (SOD), Catalase, protein level, Malondialdehyde and Nitric oxide (NO) concentration were determined by spectrophotometry. Stomach sections were immunostained for CD31 and Factor VIII (angiogenesis), p53 (apoptosis), Epidermal Growth Factor Receptor (EGFR) and Ki-67 (cell proliferation). Stomach tissue was also stained with H&E, and viewed under light microscope. All these variables were evaluated by days 3,7,14 and 21 post-induction. Data were analysed using ANOVA at α0.05. In the ulcerated control animals, the ulcer areas were 0.74 ± 0.01cm², 0.57 ± 0.08cm², 0.53 ± 0.12cm² and 0.24 ± 0.04 cm² while SA exposure significantly increased ulcer areas for 81.0%, 100.0%, 65.0%, 33.0% by days 3, 7, 14 and 21, respectively. By day 21 post-ulcer induction, zinc, Kolaviron and vitamin E had reduced ulcer areas relative to SA-treated group by 21.0%, 0.5% and 2.0%, respectively. Sodium arsenite decreased gastric mucosal thickness and parietal cell mass but increased lipid peroxidation, malondialdehyde levels and Neutrophil-Lymphocyte ratio. These effects were reversed by vitamin E and kolaviron. Total gastric acidity reduced while the levels of SOD, catalase, total protein and NO increased as healing progressed in all groups, but at a higher rate in the SA exposed group. The expression of CD31, factor VIII, Ki67 and EGFR proteins were significantly reduced by sodium arsenite, co-treatment with the antioxidants increased the labelling indices towards control values in the order zinc>kolaviron>vitamin E. The p53 expression was increased in SA treated animals but was reduced by the antioxidants in the same order. Gastric tissue necrosis, hyperplasia and haemorrhage observed in the SA-treated animals were reduced by the antioxidants. Sodium arsenite delayed gastric ulcer healing in rats via oxidative stress, inflammation, alteration in proliferative and apoptotic activities and impaired angiogenesis in the stomach.