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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
| Content Provider | Scilit |
|---|---|
| Author | El-Twab, Sanaa M. Abd Hozayen, Walaa G. Hussein, Omnia E. Mahmoud, Ayman M. |
| Copyright Year | 2016 |
| Description | 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. |
| Related Links | https://www.tandfonline.com/doi/pdf/10.1080/0886022X.2016.1216722?needAccess=true |
| Ending Page | 1527 |
| Page Count | 12 |
| Starting Page | 1516 |
| ISSN | 0886022X |
| e-ISSN | 15256049 |
| DOI | 10.1080/0886022x.2016.1216722 |
| Journal | Renal Failure |
| Issue Number | 9 |
| Volume Number | 38 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2016-08-08 |
| Access Restriction | Open |
| Subject Keyword | Journal: Renal Failure Toxicology Methotrexate Kidney Glycyrrhetinic Acid Oxidative Stress Inflammation |
| Content Type | Text |
| Resource Type | Article |
| Subject | Critical Care and Intensive Care Medicine Nephrology |
