* Corresponding author: Prof. Samy A. Hussein, Department of Biochemistry, Faculty of Veterinary Medicine, Benha University, Egypt 1 Benha Veterinary Medical Journal 38,1 (2020) 1-8 Benha Veterinary Medical Journal Journal homepage: https://bvmj.journals.ekb.eg/ Original Paper Proanthocyanidin ameliorates ethanol-induced gastric mucosal erosion by attenuating inflammatory response, oxidative stress, and apoptosis in rats Yakout A. El Senosi 1 , Mohamed K. Mahfouz 1 , Samy A. Hussein 1 , Reem A. Abd el-raouf 2 1 Department of Biochemistry, Faculty of Veterinary Medicine, Benha University, Egypt 2 Veterinarian ARTICLE INFO ABSTRACT Keywords Gastric ulcer is a common chronic disease in human digestive system. Massive alcohol drinking can lead to gastric ulcer. The gastroprotective effect and molecular mechanisms of Proanthocyanidin in a rat model of ethanol-induced gastric mucosal erosion were investigated. Thirty-five male rats were divided into five equal groups. Group 1 (Control normal): rats received no drugs. Group 2 (Early ulcer): rats received absolute ethanol (0.5 ml/100g) orally on empty stomach and sacrificed one hour later. Group 3 (Early ulcer + Proanthocyanidin protected): rats received proanthocyanidin orally at a dose of (300 mg/kg b. wt/day) for 3 weeks before ethanol administration then sacrificed after one hour. Group 4 (Late ulcer): rats received ethanol like group 2 and sacrificed after 21 days. Group 5 (Late ulcer + proanthocyanidin treated): rats first administered ethanol (0.5 ml/100g) and after one-hour proanthocyanidin was administered for 21 days. A significant increase in stomach L-MDA concentration with marked decrease in CAT activity and GSH concentration were observed in gastric erosion-induced rats. However, a significant depletion of gastric L-MDA level and marked increase in CAT activity and GSH concentration were observed after Proanthocyanidin treatment when compared to ulcerated rats. A significant up-regulation of gene expression level of BAX, NF-B and IL-1 with down- regulation of Bcl-2 gene were observed in stomach of gastric erosion-induced rats. However, a significant down regulation of BAX, NF-B and IL-1 with up-regulation of Bcl-2 gene were observed after proanthocyanidin treatment. Conclusively, proanthocyanidin protects rat gastric mucosa against ethanol-induced gastric erosion via anti-inflammatory, anti-apoptotic and anti- oxidative mechanisms. Apoptosis Gastric erosion Inflammatory mediators Oxidative stress Proanthocyanidin Received 10/01/2020 Accepted 03/02/2020 Available On-Line 18/07/2020 1. INTRODUCTION Gastric ulcers are characterized by necrosis, induction of oxidative stress and secretion of inflammatory factors (de Souza Almeida et al., 2011). The pathogenesis of gastric ulcers is based on a multifactorial and complex interaction between protective and aggressive factors, including mucosal integrity, secretion of gastric acid, Helicobacter pylori, free oxygen radicals and excess alcohol consumption (Bhattacharya et al., 2007). Disturbing the balance between aggressive and protective factors that control cell apoptosis and proliferation results in gastric ulceration, which then activates the repairing system in the gastric mucosa (Li et al., 2016). Gastric lesions are resultant of mucosal damage produced by several factors and are associated with cellular influx, free radical generation, cytokines, and growth factors. Acute inflammatory marker, myeloperoxidase (MPO), and pro-inflammatory cytokines (tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6], and IL-1 beta [IL-1]) play a major role in gastric ulceration (Kumar et al., 2013). Ethanol consumption has been shown to be a major cause of gastric ulcer. Oxidative stress and depletion of antioxidants have been considered a crucial step in alcohol-induced mucosal damage. Ethanol treatment induces intracellular oxidative stress and produces mitochondrial permeability transition and mitochondrial depolarization, which precede cell death in gastric mucosal cells. Thus, considering that ethanol is involved in the formation of oxidative stress generated extracellular and/or intra-cellular (SJ and AJ, 2015). Administration of ethanol causes gastric necrotic damage and subsequent inflammatory cell infiltration and reduces the secretion of bicarbonate, gastric mucus, and nitric oxide. In addition, ethanol reduces the gastric blood flow and induces the oxidative stress by increasing the production of malondialdehyde and reducing glutathione production (El-Maraghy et al., 2015). Intragastric administration of ethanol causes severe oxidative stress in stomach tissue by significant inhibition of the activity of antioxidant enzymes such as CAT, GPx, and SOD (Guzmán-Gómez et al., 2018) Additionally, there was a significant increase in the level of MDA (Antonisamy et al., 2015), decrease in the gastric level of nitric oxide (Abdulla et al., 2010). Pro-inflammatory cytokines such as Since 1990 Official Journal Issued by Faculty of Veterinary Medicine