title: 18β-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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: a Division of Physiology, Department of Zoology, Faculty of Science , Beni-Suef University, Beni-Suef , Egypt.
authors: Sanaa M
authors: SM
authors: Abd El-Twab
authors: 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.
authors: Walaa G
authors: WG
authors: Hozayen
authors: a Division of Physiology, Department of Zoology, Faculty of Science , Beni-Suef University, Beni-Suef , Egypt.
authors: Omnia E
authors: OE
authors: Hussein
authors: a Division of Physiology, Department of Zoology, Faculty of Science , Beni-Suef University, Beni-Suef , Egypt.
authors: Ayman M
authors: AM
authors: Mahmoud
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D017629:Gap Junctions; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000235:genetics*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D008727:Methotrexate / Q000633:toxicity; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis / Q000235:genetics*; D018384:Oxidative Stress; D012313:RNA / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; C119129:18alpha-glycyrrhetinic acid; D012313:RNA; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D006034:Glycyrrhetinic Acid; D008727:Methotrexate
keywords: Methotrexate; glycyrrhetinic acid; inflammation; kidney; oxidative stress