The Protective Effect of Testosterone on Indomethacin Induced Gastric Ulcer in Female Sprague Dawley Rats

Abstract

Gastric ulcer has shown association with changes in sex hormones, with impact exacerbated in males. Also, males are known to be more exposed to ulcer risk factors. This study investigates the effect of testosterone on indomethacin induced gastric ulcers in adult female rats. Eighteen female rats (225 ± 25 g body weight) were randomly assigned to 3 groups under standard laboratory condition. After acclimatization, animals fasted for 40 hrs but were given waterad libitum. Group A served as control while group B served as the ulcer control, in which ulcer was induced without treatment using indomethacin (40 mg/kg single orally dose). Group C was pretreated with testosterone (1 mg/kg IM) eight hours before ulcer induction. Eight hours after ulcer induction, animals were sacrificed and the stomach was harvested for analysis. Results showed a significant reduction in mucus content in groups C (0.79±0.11 g) and B (0.87±0.02 g) compared to A (1.11±0.03 g). Gastric mucus pH was significantly acidic in group B (4.40±0.55) compared to C (5.20±0.45) and A (5.80±0.45). There was a significantly higher ulcer index in group B (4.60±0.55 mm) compared to C (3.60±0.89 mm) and testosterone pretreatment resulted in a 21.74% ulcer inhibition. Although weak, the findings suggest that testosterone might protect the gastric mucosa against NSAIDs in females.

Comparative response of random and inbred albino rats to the ulcerogenic effect of indomethacin

“…These findings suggest no definite sex effect on susceptibility to indomethacin induced gastric ulceration due to high within sex variation in response in both random and inbred groups. Sexual dimorphism in susceptibility to gastric ulceration has been reported in human subjects with males being more susceptible than females (Machowska et al, 2004;Akpamu et al, 2016). This higher susceptibility has been attributed to higher exposure of males to other risk factors such as emotional stress, alcoholism, and tobacco (Akpamu et al, 2016).…”

“…Sexual dimorphism in susceptibility to gastric ulceration has been reported in human subjects with males being more susceptible than females (Machowska et al, 2004;Akpamu et al, 2016). This higher susceptibility has been attributed to higher exposure of males to other risk factors such as emotional stress, alcoholism, and tobacco (Akpamu et al, 2016). Ibrahim et al (2005) however, reported gender differences on cold restraint gastric ulceration in albino rats with intact males being more susceptible than orchidectomized males and intact females.…”

“…This observation is supported by Uslu et al (2002) who reported that differences in gastric luminal acidity did not significantly influence gastric ulceration in rats. The aetiology of gastric ulceration is believed to be multifactorial and it has been linked to inbalance between the aggressive (gastric acid, pepsin, testosterone in males, and estrogen in females) and the defensive (gastric mucus and bicarbonate secretions, prostaglandin, nitric oxide, and innate resistance of the mucosal cells) factors (Ibrahim et al, 2005;Rai et al, 2015;Akpamu et al, 2016).…”

Histological and Biochemical Study on the Estrogen Role in Indomethacin-induced Gastric Ulcer of Menopausal Rats

“…The finding confirmed by SEM and different stains. Estrogens have been shown to inhibit gastric acid secretion in female human and animal studies [19] . Oestrogen increase calcitonin gene related peptide (CGRP) levels in sensory nerve-endings leading to increased blood flow through vasodiltation.…”

“…Additionally, water access prevented for 2 h before the indomethacin dosing. Four hours after the single oral dose (40mg/kg/BW) of indomethacin, all rats were started treatment either with ranitidine alone or combined ranitidine and estradiol [19] Experimental design:…”