Abstract
Hyperammonemia is a serious complication of liver disease and may lead to encephalopathy and death. This study investigated the effects of
Commiphora molmol
resin on oxidative stress, inflammation, and hematological alterations in ammonium chloride- (NH
4
Cl-) induced hyperammonemic rats, with an emphasis on the glutamate-NO-cGMP and Nrf2/ARE/HO-1 signaling pathways. Rats received NH
4
Cl and
C. molmol
for 8 weeks. NH
4
Cl-induced rats showed significant increase in blood ammonia, liver function markers, and tumor necrosis factor-alpha (TNF-
α
). Concurrent supplementation of
C. molmol
significantly decreased circulating ammonia, liver function markers, and TNF-
α
in hyperammonemic rats.
C. molmol
suppressed lipid peroxidation and nitric oxide and enhanced the antioxidant defenses in the liver, kidney, and cerebrum of hyperammonemic rats.
C. molmol
significantly upregulated Nrf2 and HO-1 and decreased glutamine and nitric oxide synthase, soluble guanylate cyclase, and Na
+
/K
+
-ATPase expression in the cerebrum of NH
4
Cl-induced hyperammonemic rats. Hyperammonemia was also associated with hematological and coagulation system alterations. These alterations were reversed by
C. molmol
. Our findings demonstrated that
C. molmol
attenuates ammonia-induced liver injury, oxidative stress, inflammation, and hematological alterations. This study points to the modulatory effect of
C. molmol
on glutamate-NO-cGMP and Nrf2/ARE/HO-1 pathways in hyperammonemia. Therefore,
C. molmol
might be a promising protective agent against hyperammonemia.