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Possible involvement of Nrf2 and PPARγ up-regulation in the protective effect of umbelliferone against cyclophosphamide-induced hepatotoxicity.
Biomed Pharmacother. 2017 Feb; 86:297-306.BP

Abstract

Umbelliferone (UMB) is a coumarin derivative with promising hepatoprotective effects. In this study, we examined the possible protective effects of UMB against cyclophosphamide (CP)-induced hepatotoxicity, addressing the question of the possible role of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator activated receptor gamma (PPARγ). Wistar rats were orally administered UMB at doses 50 and 100mg/kg two weeks prior to CP injection. Five days after CP administration, the rats were sacrificed and samples were collected for analyses. CP induced a significant increase in circulating liver marker enzymes and pro-inflammatory cytokines. Hepatic lipid peroxidation and nitric oxide levels, and nuclear factor-kappaB (NF-κB) and inducible nitric oxide synthase (iNOS) expression were significantly increased following CP administration. UMB supplementation attenuated CP-induced inflammation and oxidative stress as assessed by restoration of the activity and expression of the antioxidant defenses, and suppression of pro-inflammatory cytokines. Histological examination also showed that UMB could significantly reduce CP-induced alterations. CP-induced rats showed significant down-regulation of Nrf2, HO-1 and PPARγ, an effect that was markedly reversed by UMB. In conclusion, the hepatoprotective effects of UMB appear to depend on co-activation of PPARγ and Nrf2, and subsequent suppression of oxidative stress and inflammation.

Authors+Show Affiliations

Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Egypt. Electronic address: ayman.mahmoud@science.bsu.edu.eg.Biology Department, Faculty of Science, Aljouf University, Saudi Arabia.Department of Physiology, College of Medicine, King Saud University, Saudi Arabia.Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28011377

Citation

Mahmoud, Ayman M., et al. "Possible Involvement of Nrf2 and PPARγ Up-regulation in the Protective Effect of Umbelliferone Against Cyclophosphamide-induced Hepatotoxicity." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 86, 2017, pp. 297-306.
Mahmoud AM, Germoush MO, Alotaibi MF, et al. Possible involvement of Nrf2 and PPARγ up-regulation in the protective effect of umbelliferone against cyclophosphamide-induced hepatotoxicity. Biomed Pharmacother. 2017;86:297-306.
Mahmoud, A. M., Germoush, M. O., Alotaibi, M. F., & Hussein, O. E. (2017). Possible involvement of Nrf2 and PPARγ up-regulation in the protective effect of umbelliferone against cyclophosphamide-induced hepatotoxicity. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 86, 297-306. https://doi.org/10.1016/j.biopha.2016.12.047
Mahmoud AM, et al. Possible Involvement of Nrf2 and PPARγ Up-regulation in the Protective Effect of Umbelliferone Against Cyclophosphamide-induced Hepatotoxicity. Biomed Pharmacother. 2017;86:297-306. PubMed PMID: 28011377.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Possible involvement of Nrf2 and PPARγ up-regulation in the protective effect of umbelliferone against cyclophosphamide-induced hepatotoxicity. AU - Mahmoud,Ayman M, AU - Germoush,Mousa O, AU - Alotaibi,Mohammed F, AU - Hussein,Omnia E, Y1 - 2016/12/21/ PY - 2016/10/13/received PY - 2016/12/11/revised PY - 2016/12/11/accepted PY - 2016/12/25/pubmed PY - 2017/2/10/medline PY - 2016/12/25/entrez KW - 7-Hydroxycoumarin KW - Cyclophosphamide KW - Hepatotoxicity KW - Nrf2 KW - Oxidative stress KW - PPARγ SP - 297 EP - 306 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 86 N2 - Umbelliferone (UMB) is a coumarin derivative with promising hepatoprotective effects. In this study, we examined the possible protective effects of UMB against cyclophosphamide (CP)-induced hepatotoxicity, addressing the question of the possible role of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator activated receptor gamma (PPARγ). Wistar rats were orally administered UMB at doses 50 and 100mg/kg two weeks prior to CP injection. Five days after CP administration, the rats were sacrificed and samples were collected for analyses. CP induced a significant increase in circulating liver marker enzymes and pro-inflammatory cytokines. Hepatic lipid peroxidation and nitric oxide levels, and nuclear factor-kappaB (NF-κB) and inducible nitric oxide synthase (iNOS) expression were significantly increased following CP administration. UMB supplementation attenuated CP-induced inflammation and oxidative stress as assessed by restoration of the activity and expression of the antioxidant defenses, and suppression of pro-inflammatory cytokines. Histological examination also showed that UMB could significantly reduce CP-induced alterations. CP-induced rats showed significant down-regulation of Nrf2, HO-1 and PPARγ, an effect that was markedly reversed by UMB. In conclusion, the hepatoprotective effects of UMB appear to depend on co-activation of PPARγ and Nrf2, and subsequent suppression of oxidative stress and inflammation. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/28011377/Possible_involvement_of_Nrf2_and_PPARγ_up_regulation_in_the_protective_effect_of_umbelliferone_against_cyclophosphamide_induced_hepatotoxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(16)31928-X DB - PRIME DP - Unbound Medicine ER -