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Commiphora molmol protects against methotrexate-induced nephrotoxicity by up-regulating Nrf2/ARE/HO-1 signaling.
Biomed Pharmacother. 2018 Oct; 106:499-509.BP

Abstract

Commiphora molmol possesses multiple therapeutic benefits against various diseases; however, its protective role against methotrexate (MTX) renal toxicity has not been previously investigated. MTX is a dihydrofolate reductase inhibitor that can induce acute kidney injury (AKI). This study evaluated the in vitro antioxidant activity and the protective effect of C. molmol resin extract against MTX-induced oxidative stress, inflammation and renal injury. Male Wistar rats received 125 and 250 mg/kg C. molmol resin extract for 15 days and a single injection of MTX at day 16. C. molmol showed a radical scavenging activity against DPPH, superoxide and nitric oxide (NO) radicals. Rats received MTX showed renal injury evidenced by the significantly elevated serum creatinine and urea, and the histological alterations. The kidney of MTX-induced rats exhibited increased lipid peroxidation, NO, NF-κB and pro-inflammatory cytokines. Pre-treatment with C. molmol prevented MTX-induced kidney injury and attenuated oxidative stress and inflammation. C. molmol down-regulated Bax and enhanced the activity and expression of the antioxidant defenses. Furthermore, the expression of Bcl-2, Nrf2, NQO-1 and HO-1 was down-regulated in the kidney of MTX-induced rats. Pre-treatment with C. molmol resin up-regulated Bcl-2 and activated Nrf2/HO-1 signaling in the kidney of MTX-induced rats. In conclusion, C. molmol resin provided protection against MTX-induced AKI via activation of Nrf2 signaling and mitigation of oxidative stress.

Authors+Show Affiliations

Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Egypt; Department of Endocrinology, Diabetes and Nutrition, Charité-University Medicine Berlin, Germany; Department of Endocrinology, Diabetes and Nutrition at the Center for Cardiovascular Research (CCR), Charité-University Medicine Berlin, Germany. Electronic address: ayman.mahmoud@science.bsu.edu.eg.Department of Biology, Faculty of Science, Jouf University, Saudi Arabia.Department of Zoology, College of Science, King Saud University, Saudi Arabia.Department of Zoology, College of Science, King Saud University, Saudi Arabia.Department of Zoology, College of Science, King Saud University, Saudi Arabia.Department of Zoology, Faculty of Science, Beni-Suef University, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29990838

Citation

Mahmoud, Ayman M., et al. "Commiphora Molmol Protects Against Methotrexate-induced Nephrotoxicity By Up-regulating Nrf2/ARE/HO-1 Signaling." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 106, 2018, pp. 499-509.
Mahmoud AM, Germoush MO, Al-Anazi KM, et al. Commiphora molmol protects against methotrexate-induced nephrotoxicity by up-regulating Nrf2/ARE/HO-1 signaling. Biomed Pharmacother. 2018;106:499-509.
Mahmoud, A. M., Germoush, M. O., Al-Anazi, K. M., Mahmoud, A. H., Farah, M. A., & Allam, A. A. (2018). Commiphora molmol protects against methotrexate-induced nephrotoxicity by up-regulating Nrf2/ARE/HO-1 signaling. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 106, 499-509. https://doi.org/10.1016/j.biopha.2018.06.171
Mahmoud AM, et al. Commiphora Molmol Protects Against Methotrexate-induced Nephrotoxicity By Up-regulating Nrf2/ARE/HO-1 Signaling. Biomed Pharmacother. 2018;106:499-509. PubMed PMID: 29990838.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Commiphora molmol protects against methotrexate-induced nephrotoxicity by up-regulating Nrf2/ARE/HO-1 signaling. AU - Mahmoud,Ayman M, AU - Germoush,Mousa O, AU - Al-Anazi,Khalid M, AU - Mahmoud,Ahmed H, AU - Farah,Mohammad Abul, AU - Allam,Ahmed A, Y1 - 2018/07/11/ PY - 2018/04/07/received PY - 2018/06/28/revised PY - 2018/06/29/accepted PY - 2018/7/11/pubmed PY - 2018/12/19/medline PY - 2018/7/11/entrez KW - Inflammation KW - Methotrexate KW - Myrrh KW - Nephrotoxicity KW - Oxidative stress SP - 499 EP - 509 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 106 N2 - Commiphora molmol possesses multiple therapeutic benefits against various diseases; however, its protective role against methotrexate (MTX) renal toxicity has not been previously investigated. MTX is a dihydrofolate reductase inhibitor that can induce acute kidney injury (AKI). This study evaluated the in vitro antioxidant activity and the protective effect of C. molmol resin extract against MTX-induced oxidative stress, inflammation and renal injury. Male Wistar rats received 125 and 250 mg/kg C. molmol resin extract for 15 days and a single injection of MTX at day 16. C. molmol showed a radical scavenging activity against DPPH, superoxide and nitric oxide (NO) radicals. Rats received MTX showed renal injury evidenced by the significantly elevated serum creatinine and urea, and the histological alterations. The kidney of MTX-induced rats exhibited increased lipid peroxidation, NO, NF-κB and pro-inflammatory cytokines. Pre-treatment with C. molmol prevented MTX-induced kidney injury and attenuated oxidative stress and inflammation. C. molmol down-regulated Bax and enhanced the activity and expression of the antioxidant defenses. Furthermore, the expression of Bcl-2, Nrf2, NQO-1 and HO-1 was down-regulated in the kidney of MTX-induced rats. Pre-treatment with C. molmol resin up-regulated Bcl-2 and activated Nrf2/HO-1 signaling in the kidney of MTX-induced rats. In conclusion, C. molmol resin provided protection against MTX-induced AKI via activation of Nrf2 signaling and mitigation of oxidative stress. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/29990838/Commiphora_molmol_protects_against_methotrexate_induced_nephrotoxicity_by_up_regulating_Nrf2/ARE/HO_1_signaling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(18)32294-7 DB - PRIME DP - Unbound Medicine ER -