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Umbelliferone prevents oxidative stress, inflammation and hematological alterations, and modulates glutamate-nitric oxide-cGMP signaling in hyperammonemic rats.
Biomed Pharmacother. 2018 Jun; 102:392-402.BP

Abstract

Hepatic encephalopathy (HE) is a serious neuropsychiatric complication that occurs as a result of liver failure. Umbelliferone (UMB; 7-hydroxycoumarin) is a natural product with proven hepatoprotective activity; however, nothing has yet been reported on its protective effect against hyperammonemia, the main culprit behind the symptoms of HE. Here, we evaluated the effect of UMB against ammonium chloride (NH4Cl)-induced hyperammonemia, oxidative stress, inflammation and hematological alterations in rats. We demonstrated the modulatory role of UMB on the glutamate-nitric oxide (NO)-cGMP pathways in the cerebrum of rats. Rats received intraperitoneal injections of NH4Cl (3 times/week) for 8 weeks and concomitantly received 50 mg/kg UMB. NH4Cl-induced rats showed significantly elevated blood ammonia and liver function markers. Lipid peroxidation and NO were increased in the liver and cerebrum of rats while the antioxidant defenses were declined. UMB significantly reduced blood ammonia, liver function markers, lipid peroxidation and NO, and enhanced the antioxidant defenses in NH4Cl-induced rats. UMB significantly prevented anemia, leukocytosis, thrombocytopenia and prolongation of PT and aPTT. Hyperammonemic rats showed elevated levels of cerebral TNF-α, IL-1β and glutamine as well as increased activity and expression of Na+/K+-ATPase, effects that were significantly reversed by UMB. In addition, UMB down-regulated nitric oxide synthase and soluble guanylate cyclase in the cerebrum of hyperammonemic rats. In conclusion, this study provides evidence that UMB protects against hyperammonemia via attenuation of oxidative stress and inflammation. UMB prevents hyperammonemia associated hematological alterations and therefore represents a promising protective agent against the deleterious effects of excess ammonia.

Authors+Show Affiliations

Biology Department, Faculty of Science, Jouf University, Aljouf, Saudi Arabia.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.Biology Department, Faculty of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia.Physiology Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia.Biology Department, Faculty of Science, Jouf University, Aljouf, Saudi Arabia.Biomedical Sciences Department, Faculty of Veterinary & Animal Sciences, PMAS, Arid Agriculture University, Rawalpindi, Pakistan.Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt; Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt. Electronic address: ayman.mahmoud@science.bsu.edu.eg.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29573618

Citation

Germoush, Mousa O., et al. "Umbelliferone Prevents Oxidative Stress, Inflammation and Hematological Alterations, and Modulates Glutamate-nitric oxide-cGMP Signaling in Hyperammonemic Rats." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 102, 2018, pp. 392-402.
Germoush MO, Othman SI, Al-Qaraawi MA, et al. Umbelliferone prevents oxidative stress, inflammation and hematological alterations, and modulates glutamate-nitric oxide-cGMP signaling in hyperammonemic rats. Biomed Pharmacother. 2018;102:392-402.
Germoush, M. O., Othman, S. I., Al-Qaraawi, M. A., Al-Harbi, H. M., Hussein, O. E., Al-Basher, G., Alotaibi, M. F., Elgebaly, H. A., Sandhu, M. A., Allam, A. A., & Mahmoud, A. M. (2018). Umbelliferone prevents oxidative stress, inflammation and hematological alterations, and modulates glutamate-nitric oxide-cGMP signaling in hyperammonemic rats. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 102, 392-402. https://doi.org/10.1016/j.biopha.2018.03.104
Germoush MO, et al. Umbelliferone Prevents Oxidative Stress, Inflammation and Hematological Alterations, and Modulates Glutamate-nitric oxide-cGMP Signaling in Hyperammonemic Rats. Biomed Pharmacother. 2018;102:392-402. PubMed PMID: 29573618.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Umbelliferone prevents oxidative stress, inflammation and hematological alterations, and modulates glutamate-nitric oxide-cGMP signaling in hyperammonemic rats. AU - Germoush,Mousa O, AU - Othman,Sarah I, AU - Al-Qaraawi,Maha A, AU - Al-Harbi,Hanan M, AU - Hussein,Omnia E, AU - Al-Basher,Gadh, AU - Alotaibi,Mohammed F, AU - Elgebaly,Hassan A, AU - Sandhu,Mansur A, AU - Allam,Ahmed A, AU - Mahmoud,Ayman M, Y1 - 2018/03/22/ PY - 2017/09/28/received PY - 2018/03/02/revised PY - 2018/03/17/accepted PY - 2018/3/25/pubmed PY - 2018/10/12/medline PY - 2018/3/25/entrez KW - 7-Hydroxycoumarin KW - Ammonia KW - Inflammation KW - Na(+)/K(+)-ATPase KW - Nitric oxide KW - Oxidative stress SP - 392 EP - 402 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 102 N2 - Hepatic encephalopathy (HE) is a serious neuropsychiatric complication that occurs as a result of liver failure. Umbelliferone (UMB; 7-hydroxycoumarin) is a natural product with proven hepatoprotective activity; however, nothing has yet been reported on its protective effect against hyperammonemia, the main culprit behind the symptoms of HE. Here, we evaluated the effect of UMB against ammonium chloride (NH4Cl)-induced hyperammonemia, oxidative stress, inflammation and hematological alterations in rats. We demonstrated the modulatory role of UMB on the glutamate-nitric oxide (NO)-cGMP pathways in the cerebrum of rats. Rats received intraperitoneal injections of NH4Cl (3 times/week) for 8 weeks and concomitantly received 50 mg/kg UMB. NH4Cl-induced rats showed significantly elevated blood ammonia and liver function markers. Lipid peroxidation and NO were increased in the liver and cerebrum of rats while the antioxidant defenses were declined. UMB significantly reduced blood ammonia, liver function markers, lipid peroxidation and NO, and enhanced the antioxidant defenses in NH4Cl-induced rats. UMB significantly prevented anemia, leukocytosis, thrombocytopenia and prolongation of PT and aPTT. Hyperammonemic rats showed elevated levels of cerebral TNF-α, IL-1β and glutamine as well as increased activity and expression of Na+/K+-ATPase, effects that were significantly reversed by UMB. In addition, UMB down-regulated nitric oxide synthase and soluble guanylate cyclase in the cerebrum of hyperammonemic rats. In conclusion, this study provides evidence that UMB protects against hyperammonemia via attenuation of oxidative stress and inflammation. UMB prevents hyperammonemia associated hematological alterations and therefore represents a promising protective agent against the deleterious effects of excess ammonia. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/29573618/Umbelliferone_prevents_oxidative_stress_inflammation_and_hematological_alterations_and_modulates_glutamate_nitric_oxide_cGMP_signaling_in_hyperammonemic_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(17)35063-1 DB - PRIME DP - Unbound Medicine ER -