Freshwater Clam Extract Attenuates Indomethacin-Induced Gastric Damage In Vitro and In Vivo

Abstract

Contemporary pharmacological studies have reported that freshwater clam (Corbicula fluminea) can provide a broad spectrum of bioactivities, including antioxidant, anticancer, antihypertensive, hepatoprotective, and hypocholesterolemic effects. The aim of this study was to evaluate the gastroprotective effects of water extract of freshwater clam (WEC) on indomethacin (IND)-induced gastric mucosal cell damage in vitro and gastric ulcer in vivo. The cell viability of rat gastric mucosa RGM-1 cells was markedly decreased by 0.8 mM of IND treatment, and pre-treated with various concentration of WEC significantly restored IND-induced cell damage in a dose-dependent manner. WEC also significantly attenuated the elevated reactive oxygen species (ROS) levels, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, and nuclear factor-κB (NF-κB) p65 nuclear translocation induced by IND. In the in vivo study, IND caused severe gastric ulcer in Wistar rats, while WEC pretreatment effectively reduced the ulcer area and edema in the submucosa. We found that WEC significantly restored glutathione (GSH) content in gastric mucosa in a dose-dependent manner (p < 0.05). The reduction of prostaglandin E2 (PGE2) caused by IND was also improved with higher doses of WEC administration. Moreover, the overexpression of COX-2, iNOS, and tumor necrosis factor-α (TNF-α) proteins in gastric mucosa was downregulated by administration of WEC. Consequently, WEC can be used as a potential nutritional supplement to improve NSAIDs-caused gastric mucosal lesions.