The aims of this study were to explore whether a phenolic acid and flavonoid fraction (named PAFF) isolated from Lolium multiflorum Lam. protects against d-galactosamine (GalN)-induced liver damages in mice and to investigate the associated mechanisms. ICR mice received oral administration with various concentrations (50, 100, and 200 mg/kg body weight) of PAFF once per 2 days for seven times before intraperitoneal injection with 800 mg/kg GalN. After a day of GalN challenge, blood and tissue samples were analyzed by biochemical, histopathological, real time RT-PCR, and Western blot methods. GalN challenge induced severe damage to hepatocytes with hepatocellular vacuolization and necrosis. GalN treatment increased serum ALT, ALP, AST, and LDH levels and hepatic MDA levels and stimulated mRNA and protein expressions of Nrf2 and HO-1 in the liver. GalN treatment also diminished the levels of GSH and the activities of CAT, SOD, and GPx in the liver. However, combined treatment with PAFF inhibited GalN-mediated increases in the histological damages and the levels of serum enzymes and hepatic MDA, restored the activities of hepatic antioxidant enzymes up to those in the control values, and augmented the GalN-stimulated expression of Nrf2 and HO-1 in the liver. Furthermore, PAFF treatment alone increased the cellular SOD activity and the expression of Nrf2 and HO-1 in the liver. Our results suggest that PAFF may protect against GalN-induced liver damage by decreasing oxidative stress and increasing cellular antioxidant activities through an activation of Nrf2/HO-1-dependent pathway.
Italian ryegrass d-Galactosamine Hepatic damage Nrf2 Bioactive compounds
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This work was supported by a grant from the Rural Development Administration, Ministry of Agriculture and Forestry, South Korea (Grant No.: PJ010903032015).
Compliance with Ethical Standards
Conflict of interest
Young-Ok Son, Jung-Min Hwang, Ki-Choon Choi and Jeong-Chae Lee declares that they have no conflict of interest.
Human and Animal Rights
This study was carried out in strict accordance with the recommendations in the Guide for the Animal Care and Use of the Chonbuk National University. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The protocol in this study was approved by the University Committee on Ethics in the Care and Use of Laboratory Animals (Permit No. CBU 2012–0039).
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