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18β-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants.
Ren Fail. 2016 Oct; 38(9):1516-1527.RF

Abstract

OBJECTIVES

18β-glycyrrhetinic acid (18β-GA) has multiple beneficial and therapeutic effects. However, its protective roles on methotrexate (MTX)-induced renal injury are not well defined. In the present study, we investigated the possible protective effects of 18β-GA against MTX-induced nephrotoxicity in rats.

MATERIALS

18β-GA (50 and 100 mg/kg) was administered for 7 days either before or after MTX. The rats were decapitated and kidney and serum samples were collected.

RESULTS

MTX-induced renal injury in rats was evidenced by the significant (p < 0.001) increase in circulating kidney function markers and tumor necrosis factor alpha (TNF-α), as well as the histopathological alterations. MTX-induced rats exhibited significantly increased lipid peroxidation (p < 0.05) and nitric oxide (p < 0.001) levels, with concomitant marked (p < 0.001) decline in the antioxidant defenses. 18β-GA, administered either before or after MTX, produced a significant amelioration of circulating kidney function markers, TNF-α, kidney lipid peroxidation, nitric oxide, and antioxidant defenses. In addition, 18β-GA supplementation significantly up-regulated the mRNA abundance of both nuclear factor-erythroid 2-related factor 2 (Nrf2) and hemoxygenase 1 (HO-1) in the kidney of MTX-induced rats.

CONCLUSIONS

These results indicate that 18β-GA has a protective effect on MTX-induced nephrotoxicity with possible mechanisms of attenuating oxidative stress and inflammation through up-regulating the Nrf2/ARE signaling. These findings make 18β-GA candidate as a potent agent in preventing MTX-induced kidney injury.

Authors+Show Affiliations

a Division of Physiology, Department of Zoology, Faculty of Science , Beni-Suef University, Beni-Suef , Egypt.b Division of Biochemistry, Department of Chemistry, Faculty of Science , Beni-Suef University, Beni-Suef , Egypt. c Department of Biotechnology & Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences (PSAS) , Beni-Suef University , Beni-Suef , Egypt.a Division of Physiology, Department of Zoology, Faculty of Science , Beni-Suef University, Beni-Suef , Egypt.a Division of Physiology, Department of Zoology, Faculty of Science , Beni-Suef University, Beni-Suef , Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27499091

Citation

Abd El-Twab, Sanaa M., et al. "18β-Glycyrrhetinic Acid Protects Against Methotrexate-induced Kidney Injury By Up-regulating the Nrf2/ARE/HO-1 Pathway and Endogenous Antioxidants." Renal Failure, vol. 38, no. 9, 2016, pp. 1516-1527.
Abd El-Twab SM, Hozayen WG, Hussein OE, et al. 18β-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants. Ren Fail. 2016;38(9):1516-1527.
Abd El-Twab, S. M., Hozayen, W. G., Hussein, O. E., & Mahmoud, A. M. (2016). 18β-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants. Renal Failure, 38(9), 1516-1527.
Abd El-Twab SM, et al. 18β-Glycyrrhetinic Acid Protects Against Methotrexate-induced Kidney Injury By Up-regulating the Nrf2/ARE/HO-1 Pathway and Endogenous Antioxidants. Ren Fail. 2016;38(9):1516-1527. PubMed PMID: 27499091.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 18β-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants. AU - Abd El-Twab,Sanaa M, AU - Hozayen,Walaa G, AU - Hussein,Omnia E, AU - Mahmoud,Ayman M, Y1 - 2016/08/08/ PY - 2016/11/4/pubmed PY - 2017/4/12/medline PY - 2016/8/9/entrez KW - Methotrexate KW - glycyrrhetinic acid KW - inflammation KW - kidney KW - oxidative stress SP - 1516 EP - 1527 JF - Renal failure JO - Ren Fail VL - 38 IS - 9 N2 - OBJECTIVES: 18β-glycyrrhetinic acid (18β-GA) has multiple beneficial and therapeutic effects. However, its protective roles on methotrexate (MTX)-induced renal injury are not well defined. In the present study, we investigated the possible protective effects of 18β-GA against MTX-induced nephrotoxicity in rats. MATERIALS: 18β-GA (50 and 100 mg/kg) was administered for 7 days either before or after MTX. The rats were decapitated and kidney and serum samples were collected. RESULTS: MTX-induced renal injury in rats was evidenced by the significant (p < 0.001) increase in circulating kidney function markers and tumor necrosis factor alpha (TNF-α), as well as the histopathological alterations. MTX-induced rats exhibited significantly increased lipid peroxidation (p < 0.05) and nitric oxide (p < 0.001) levels, with concomitant marked (p < 0.001) decline in the antioxidant defenses. 18β-GA, administered either before or after MTX, produced a significant amelioration of circulating kidney function markers, TNF-α, kidney lipid peroxidation, nitric oxide, and antioxidant defenses. In addition, 18β-GA supplementation significantly up-regulated the mRNA abundance of both nuclear factor-erythroid 2-related factor 2 (Nrf2) and hemoxygenase 1 (HO-1) in the kidney of MTX-induced rats. CONCLUSIONS: These results indicate that 18β-GA has a protective effect on MTX-induced nephrotoxicity with possible mechanisms of attenuating oxidative stress and inflammation through up-regulating the Nrf2/ARE signaling. These findings make 18β-GA candidate as a potent agent in preventing MTX-induced kidney injury. SN - 1525-6049 UR - https://www.unboundmedicine.com/medline/citation/27499091/18β_Glycyrrhetinic_acid_protects_against_methotrexate_induced_kidney_injury_by_up_regulating_the_Nrf2/ARE/HO_1_pathway_and_endogenous_antioxidants_ L2 - https://www.tandfonline.com/doi/full/10.1080/0886022X.2016.1216722 DB - PRIME DP - Unbound Medicine ER -