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Commiphora molmol Modulates Glutamate-Nitric Oxide-cGMP and Nrf2/ARE/HO-1 Pathways and Attenuates Oxidative Stress and Hematological Alterations in Hyperammonemic Rats.
Oxid Med Cell Longev. 2017; 2017:7369671.OM

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- (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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28744340

Citation

Mahmoud, Ayman M., et al. "Commiphora Molmol Modulates Glutamate-Nitric Oxide-cGMP and Nrf2/ARE/HO-1 Pathways and Attenuates Oxidative Stress and Hematological Alterations in Hyperammonemic Rats." Oxidative Medicine and Cellular Longevity, vol. 2017, 2017, p. 7369671.
Mahmoud AM, Alqahtani S, Othman SI, et al. Commiphora molmol Modulates Glutamate-Nitric Oxide-cGMP and Nrf2/ARE/HO-1 Pathways and Attenuates Oxidative Stress and Hematological Alterations in Hyperammonemic Rats. Oxid Med Cell Longev. 2017;2017:7369671.
Mahmoud, A. M., Alqahtani, S., Othman, S. I., Germoush, M. O., Hussein, O. E., Al-Basher, G., Khim, J. S., Al-Qaraawi, M. A., Al-Harbi, H. M., Fadel, A., & Allam, A. A. (2017). Commiphora molmol Modulates Glutamate-Nitric Oxide-cGMP and Nrf2/ARE/HO-1 Pathways and Attenuates Oxidative Stress and Hematological Alterations in Hyperammonemic Rats. Oxidative Medicine and Cellular Longevity, 2017, 7369671. https://doi.org/10.1155/2017/7369671
Mahmoud AM, et al. Commiphora Molmol Modulates Glutamate-Nitric Oxide-cGMP and Nrf2/ARE/HO-1 Pathways and Attenuates Oxidative Stress and Hematological Alterations in Hyperammonemic Rats. Oxid Med Cell Longev. 2017;2017:7369671. PubMed PMID: 28744340.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Commiphora molmol Modulates Glutamate-Nitric Oxide-cGMP and Nrf2/ARE/HO-1 Pathways and Attenuates Oxidative Stress and Hematological Alterations in Hyperammonemic Rats. AU - Mahmoud,Ayman M, AU - Alqahtani,Sultan, AU - Othman,Sarah I, AU - Germoush,Mousa O, AU - Hussein,Omnia E, AU - Al-Basher,Gadh, AU - Khim,Jong Seong, AU - Al-Qaraawi,Maha A, AU - Al-Harbi,Hanan M, AU - Fadel,Abdulmannan, AU - Allam,Ahmed A, Y1 - 2017/06/28/ PY - 2017/03/01/received PY - 2017/05/21/revised PY - 2017/05/28/accepted PY - 2017/7/27/entrez PY - 2017/7/27/pubmed PY - 2018/4/10/medline SP - 7369671 EP - 7369671 JF - Oxidative medicine and cellular longevity JO - Oxid Med Cell Longev VL - 2017 N2 - 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. SN - 1942-0994 UR - https://www.unboundmedicine.com/medline/citation/28744340/Commiphora_molmol_Modulates_Glutamate_Nitric_Oxide_cGMP_and_Nrf2/ARE/HO_1_Pathways_and_Attenuates_Oxidative_Stress_and_Hematological_Alterations_in_Hyperammonemic_Rats_ L2 - https://doi.org/10.1155/2017/7369671 DB - PRIME DP - Unbound Medicine ER -