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Mahmoud, Ayman M.,Alqahtani, Sultan,Othman, Sarah I.,Germoush, Mousa O.,Hussein, Omnia E.,Al-Basher, Gadh,Khim, Jong Seong,Al-Qaraawi, Maha A.,Al-Harbi, Hanan M.,Fadel, Abdulmannan,Allam, Ahmed A. Hindawi 2017 Oxidative medicine and cellular longevity Vol.2017 No.-
<P>Hyperammonemia is a serious complication of liver disease and may lead to encephalopathy and death. This study investigated the effects of <I>Commiphora molmol</I> resin on oxidative stress, inflammation, and hematological alterations in ammonium chloride- (NH<SUB>4</SUB>Cl-) induced hyperammonemic rats, with an emphasis on the glutamate-NO-cGMP and Nrf2/ARE/HO-1 signaling pathways. Rats received NH<SUB>4</SUB>Cl and <I>C. molmol</I> for 8 weeks. NH<SUB>4</SUB>Cl-induced rats showed significant increase in blood ammonia, liver function markers, and tumor necrosis factor-alpha (TNF-<I>α</I>). Concurrent supplementation of <I>C. molmol</I> significantly decreased circulating ammonia, liver function markers, and TNF-<I>α</I> in hyperammonemic rats. <I>C. molmol</I> suppressed lipid peroxidation and nitric oxide and enhanced the antioxidant defenses in the liver, kidney, and cerebrum of hyperammonemic rats. <I>C. molmol</I> significantly upregulated Nrf2 and HO-1 and decreased glutamine and nitric oxide synthase, soluble guanylate cyclase, and Na<SUP>+</SUP>/K<SUP>+</SUP>-ATPase expression in the cerebrum of NH<SUB>4</SUB>Cl-induced hyperammonemic rats. Hyperammonemia was also associated with hematological and coagulation system alterations. These alterations were reversed by <I>C. molmol</I>. Our findings demonstrated that <I>C. molmol</I> attenuates ammonia-induced liver injury, oxidative stress, inflammation, and hematological alterations. This study points to the modulatory effect of <I>C. molmol</I> on glutamate-NO-cGMP and Nrf2/ARE/HO-1 pathways in hyperammonemia. Therefore, <I>C. molmol</I> might be a promising protective agent against hyperammonemia.</P>