Gastroprotective Effect of Azilsartan Through Ameliorating Oxidative Stress, Inflammation, and Restoring Hydroxyproline, and Gastrin Levels in Ethanol-Induced Gastric Ulcer.

Abstract

ObjectiveThe present study was designed to evaluate the possible gastroprotective effects of different doses of azilsartan in ethanol-induced gastric ulcers in rats.MethodologyForty-eight male adult Wistar rats were used and allocated randomly into four groups: negative control treated with distilled water, positive control treated with ethanol, lansoprazole treated group, and azilsartan (1mg, 5mg, and 10mg/kg) treated group. The treatment protocol was for 15 days, and all the groups except for the negative control group received 1mL of ethanol on the last day 1hr before scarification. Gastric content was collected for measuring the volume, free acidity, and pH. The stomach was used for measuring the gastric lesion area and ulcer index. Blood samples were collected for measuring serum hydroxyproline, gastrin, CRP, TNF-α, MDA, and TAOC. Gastric tissues were sent for histopathological examinations.ResultsEthanol administration significantly increased gastric lesion, gastric ulcer index, and gastric acidity. Ethanol also decreased serum levels of hydroxyproline and TAOC and increased serum gastrin, CRP, TNF-α, and MDA. Azilsartan 10mg/kg was able to decrease the lesion by 43.6% and increase gastric pH and significantly decreased MDA level. Both 5mg/kg and 10mg/kg azilsartan have successfully restored the level of hydroxyproline, gastrin, and TNF-α. The histopathological finding showed gastroprotection by azilsartan in a dose-dependent manner.ConclusionThe study revealed that azilsartan possesses a gastroprotective effect. The proposed mechanisms could be increased blood flow to the stomach, antioxidant capacity, and anti-inflammatory activity along with restoring hydroxyproline and gastrin levels. These findings suggest azilsartan as a promising candidate to be tested in a clinical setting.