Acacetin ameliorates acetylsalicylic acid-induced gastric ulcer in rats by interfering with oxidative stress, inflammation, and apoptosis

Abstract

Objectives: Gastric ulcer (GU) is a benign lesion in which excessive acid and pepsin activity affects the mucosal epithelium and is common worldwide. Gastrointestinal disturbances come to the fore among the side effects observed in the treatment with drugs such as aspirin. Acacetin is a plant-derived flavonoid with intriguing properties such as anti-inflammatory, antioxidant, and anticancer. The aim of the study is to investigate the effects of acacetin in GU model caused by aspirin active ingredient acetylsalicylic acid. Methods: Thirty-two Wistar albino rats were divided into four groups: Control, GU, acacetin, and GU +acacetin. Acetylsalicylic acid (150 mg/kg) and acacetin (25 mg/kg) were administered intraperitoneally as a single dose. Gastric lesions were examined microscopically and macroscopically. TNF-a, cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-kB) for inflammation; Caspase-3 and Bcl-2 for apoptosis, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) for oxidative stress were analyzed. Results: Bcl-2 and TAS values were decreased, while Tumor necrosis factor-alpha (TNF-α), COX-2, NF-kB, Caspase-3, TOS, and OSI values were increased in the GU group compared to the control group. Bcl-2 and TAS values were increased and TNF-α, COX-2, NF-kB, Caspase-3, TOS, and OSI values were decreased in the GU +acacetin group compared to the GU group. The GU index (GUI) detected in the GU group decreased significantly with the administration of acacetin. Conclusion: High doses of ASA contributed to the formation of GU in the stomach tissue by increasing the levels of inflammation, oxidative stress, and apoptosis, whereas ACA reduced the ulcer damage by reducing the increase in all these pathways.