Acute Toxicity and Gastroprotection Studies with a Newly Synthesized Steroid

Abstract

BackgroundSynthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S)-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3′H-cyclopropa[3α,5]-5α-pregnane (AMDCP), on ethanol-induced gastric mucosa injuries in rats.Methodology/Principal FindingRats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE2) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE2 as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes.Conclusion/SignificanceThe current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent.

RETRACTED ARTICLE: The gastro protective effects of Cibotium barometz hair on ethanol-induced gastric ulcer in Sprague-Dawley rats

“…The rats treated with C. barometz hair extract displayed a mild distraction of stomach epithelium and reduced edema and inflammatory cell penetration of the submucosal layers. Similarly, many studies have also observed mild distraction of stomach mucosa, mild edema and penetration of inflammatory cells in the submucosal layers [31–35]. Additionally, the condensing of the submucosal layer was detected in the ulcerated group where there was edema and hemorrhagic abrasions in the mucosal layer, which is an indicator of ethanol damage.…”

Gastroprotective Activity of Ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylidene) Amino]benzoate against Ethanol-Induced Gastric Mucosal Ulcer in Rats

“…This corresponds to the observed IC 50 0f 141.20±0.02 µg/mL in NO and 73.1±0.12 in metal chelating assays (Table 1). The observed antioxidant activity of this compound could be the reason for its anti-ulcerogenic efficacy [14]. Indeed, Gwaram et al [43] have illustrated the mechanism of Schiff base anti-oxidant cyto-protective activity to be through the presence of the carbonyl group (a well-known electrophilic acceptor) in the compounds, which appears to achieve antioxidant balance and to protect the gastric mucosa from injurious agents.…”

Gastroprotection Studies of Schiff Base Zinc (II) Derivative Complex against Acute Superficial Hemorrhagic Mucosal Lesions in Rats

“…Several studies have promoted ethanol-induced model of hemorrhagic gastric lesions [34], [51]–[53]. It has been established that one of the most important detrimental effects evoked by ethanol-induced gastric lesion is represented by increments of gastric mucosal MDA levels, a marker for oxidative stress [54].…”

“…Previous studies showed that several gastroprotective mechanisms were involved in the protection of gastric tissue against aggressive conditions [25], [30], [34]. The acidity of gastric juice, gastric wall mucosa, antioxidant and enzymatic activities of the stomach were assessed to identify protective mechanisms of zinc (II) complex in the ethanol-induced gastric lesions in rats.…”

“…Several natural/synthetic agents introduced with protective effects against acute hemorrhagic gastric lesions possessed free-radical scavenging activity [29]–[33]. The antioxidant activity of several ingredients might augment the total antioxidant activity of the tissue [30], [34]. Another protective mechanism is the suppression of acid secretion which have been considered a preventive strategy against gastric superficial hemorrhagic mucosal lesions.…”