Glabridin ameliorates methotrexate-induced liver injury via attenuation of oxidative stress, inflammation, and apoptosis.

Abstract

Despite unprecedented advances in modern medicine, no safe and effective drug is available to date for oral administration to combat drug-induced liver injury, which is a vital concern nowadays. The present study deals with the hepatoprotective effect of pure glabridin, a key phytoconstituent from Glycyrrhiza glabra with mechanistic investigations using an in-vivo methotrexate-induced liver injury model as there is no such precedent. The study was performed in the Swiss mice model where a single dose of methotrexate (40 mg/kg) was given on the 7th day through an intraperitoneal route to induce hepatotoxicity, and glabridin as a test compound was administered orally for eleven consecutive days at 10 to 40 mg/kg. Glabridin markedly improved serum biochemical parameters (SGPT, SGOT), proinflammatory cytokine (TNF-α) level, oxidative stress markers (MDA, GSH, SOD, CAT) as compared to methotrexate alone. Alterations in methotrexate-induced liver architecture were considerably prevented by glabridin treatment as suggested by liver histopathological examination and SEM investigation. Glabridin substantially prevented methotrexate-induced down-regulation of Nrf2, & activation of NF-κB, and caused up-regulation of BAX at different dose levels. Overall, glabridin is found to protect methotrexate-induced hepatotoxicity by improving important factors for oxidative stress, inflammation, and apoptosis.

• Authors: Ashish Dogra, Divya Gupta, Swarnendu Bag, Irfan Ahmed, Shipra Bhatt, Ekta Nehra, Shakti Dhiman, Amit Kumar, Gurdarshan Singh, Sheikh Tasduq Abdullah, Payare Lal Sangwan, Utpal Nandi
• Journal: Life sciences (Life Sci) Vol. 278 Pg. 119583 (Aug 01 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 33957170 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Antioxidants
• Isoflavones
• NF-kappa B
• Phenols
• Protective Agents
• Tumor Necrosis Factor-alpha
• glabridin
• Methotrexate

Topics

• Animals
• Antioxidants (pharmacology)
• Apoptosis
• Chemical and Drug Induced Liver Injury (pathology)
• Chemical and Drug Induced Liver Injury, Chronic (drug therapy, metabolism)
• Down-Regulation
• Glycyrrhiza
• Humans
• Inflammation (therapy)
• Isoflavones (pharmacology)
• Liver (drug effects, injuries, metabolism)
• Methotrexate
• Mice
• NF-kappa B (metabolism)
• Oxidative Stress
• Phenols (pharmacology)
• Protective Agents (pharmacology)
• Tumor Necrosis Factor-alpha (metabolism)