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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 7369671, 15 pages
Research Article

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

1Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni Suef, Egypt
2Department of Endocrinology, Diabetes & Nutrition, Charité-University Medicine Berlin, Germany
3College of Medicine, King Saud Bin Abdulaziz University for Health Science (KSAU-HS), Riyadh, Saudi Arabia
4King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia
5Biology Department, Faculty of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
6Biology Department, Faculty of Science, Aljouf University, Sakakah, Aljouf, Saudi Arabia
7Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia
8School of Earth and Environmental Sciences & Research Institute of Oceanography, Seoul National University, Seoul, Republic of Korea
9School of Healthcare Science, Manchester Metropolitan University, Manchester, UK
10Zoology Department, Faculty of Science, Beni-Suef University, Beni Suef, Egypt

Correspondence should be addressed to Ayman M. Mahmoud; ge.ude.usb.ecneics@duomham.namya

Received 1 March 2017; Revised 21 May 2017; Accepted 28 May 2017; Published 28 June 2017

Academic Editor: Tiziana Persichini

Copyright © 2017 Ayman M. Mahmoud et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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- (NH4Cl-) induced hyperammonemic rats, with an emphasis on the glutamate-NO-cGMP and Nrf2/ARE/HO-1 signaling pathways. Rats received NH4Cl and C. molmol for 8 weeks. NH4Cl-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 NH4Cl-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.