Coumarin-Induced Delay in Gastrointestinal Transit Through Facilitation of Nitrergic Neurotransmission in Male Albino Rats

Coumarin, a natural plant-derived benzopyrone compound, is widely known for its anticoagulant, anti-inflammatory, and vasodilatory properties. Humans are often exposed to Coumarin through consumption of Coumarin tainted foods. Upon exposure, the small intestine gets primarily exposed to Coumarin, and it might exert its effects on the small intestine. Thus, the goal of this study was to examine the influence of Coumarin-induced changes in contractile activity of the small intestine in vivo by assessing gastrointestinal transit using the charcoal meal test. Our study indicated that animals exposed to Coumarin had significantly lowered gastrointestinal transit rates compared to control rats. Coumarin inhibits small intestinal transit by inhibiting the contractions of the visceral smooth muscles located in the muscularis externa layer of the small intestine that provides motility to the small intestine. However, intraperitoneal administration of L-NAME and Methylene Blue significantly reverse inhibitory effect of Coumarin on the gastrointestinal transit. In conclusion, it could be suggested that Coumarin may reduce gastrointestinal transit by inhibiting smooth muscle contractions at the small intestinal wall probably by activating nitrergic intrinsic myenteric efferents that secrete nitric oxide. These findings highlight the potential therapeutic application of coumarin in conditions associated with hypermotility and point to nitrergic signaling as its primary mechanism of action. Keywords: Coumarin, Gastrointestinal transit, nitric oxide, L-NAME, nitrergic signaling.