Commiphora molmolModulates Glutamate-Nitric Oxide-cGMP and Nrf2/ARE/HO-1 Pathways and Attenuates Oxidative Stress and Hematological Alterations in Hyperammonemic Rats

Abstract

Hyperammonemia is a serious complication of liver disease and may lead to encephalopathy and death. This study investigated the effects ofCommiphora molmolresin on oxidative stress, inflammation, and hematological alterations in ammonium chloride- (NH4Cl-) induced hyperammonemic rats, with an emphasis on the glutamate-NO-cGMP and Nrf2/ARE/HO-1 signaling pathways. Rats received NH4Cl andC. molmolfor 8 weeks. NH4Cl-induced rats showed significant increase in blood ammonia, liver function markers, and tumor necrosis factor-alpha (TNF-α). Concurrent supplementation ofC. molmolsignificantly decreased circulating ammonia, liver function markers, and TNF-αin hyperammonemic rats.C. molmolsuppressed lipid peroxidation and nitric oxide and enhanced the antioxidant defenses in the liver, kidney, and cerebrum of hyperammonemic rats.C. molmolsignificantly upregulated Nrf2 and HO-1 and decreased glutamine and nitric oxide synthase, soluble guanylate cyclase, and Na+/K+-ATPase expression in the cerebrum of NH4Cl-induced hyperammonemic rats. Hyperammonemia was also associated with hematological and coagulation system alterations. These alterations were reversed byC. molmol. Our findings demonstrated thatC. molmolattenuates ammonia-induced liver injury, oxidative stress, inflammation, and hematological alterations. This study points to the modulatory effect ofC. molmolon glutamate-NO-cGMP and Nrf2/ARE/HO-1 pathways in hyperammonemia. Therefore,C. molmolmight be a promising protective agent against hyperammonemia.