1. Glabridin ameliorates methotrexate-induced liver injury via attenuation of oxidative stress, inflammation, and apoptosis.
- Author
-
Dogra A, Gupta D, Bag S, Ahmed I, Bhatt S, Nehra E, Dhiman S, Kumar A, Singh G, Abdullah ST, Sangwan PL, and Nandi U
- Subjects
- Animals, Antioxidants pharmacology, Chemical and Drug Induced Liver Injury pathology, Chemical and Drug Induced Liver Injury, Chronic metabolism, Down-Regulation, Glycyrrhiza, Humans, Liver injuries, Liver metabolism, Methotrexate, Mice, NF-kappa B metabolism, Protective Agents pharmacology, Tumor Necrosis Factor-alpha metabolism, Apoptosis, Chemical and Drug Induced Liver Injury, Chronic drug therapy, Inflammation therapy, Isoflavones pharmacology, Liver drug effects, Oxidative Stress, Phenols pharmacology
- 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 7
th 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., (Copyright © 2021. Published by Elsevier Inc.)- Published
- 2021
- Full Text
- View/download PDF