Naringin protects against perfluorooctane sulfonate-induced liver injury by modulating NRF2 and NF-κB in mice

• Published in: International immunopharmacology Vol. 65; pp. 140 - 147
• Main Authors: Lv, Zehui, Wu, Wenyao, Ge, Shuna, Jia, Rui, Lin, Tingting, Yuan, Yangyang, Kuang, Haibin, Yang, Bei, Wu, Lei, Wei, Jie, Zhang, Dalei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2018; Elsevier BV
• Subjects: Alkanesulfonic Acids - toxicity; Animal tissues; Animals; Apoptosis; BAX protein; Bcl-2 protein; Caspase; Catalase; Chemical and Drug Induced Liver Injury - prevention & control; Cytokines; Enzymatic activity; Enzymes; Flavanones - pharmacology; Fluorocarbons - toxicity; Gene expression; Gene Expression Regulation - drug effects; Heme; Hepatotoxicity; Hydrogen peroxide; Inflammation; Interleukin 6; Liver; Liver - drug effects; Liver - metabolism; Male; Malondialdehyde; Mice; Naringin; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB protein; NRF2 protein; Oxidative stress; Oxygenase; Perfluorooctane sulfonate; Perfluorooctane sulfonic acid; Pollutants; Protective Agents - pharmacology; Proteins; Superoxide dismutase; Supplements; Toxicity; Tumor necrosis factor-α; Up-Regulation; Weight; Oxidative stress; Perfluorooctane sulfonate; Inflammation; Naringin; Hepatotoxicity; Apoptosis
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2018.09.019

Perfluorooctane sulfonate (PFOS), a persistent organic pollutant, has been demonstrated to cause multiple toxicities. In this study, we explored the role of naringin (Nar) in alleviating PFOS-caused mouse liver injury and its potential mechanisms. Male mice were intragastrically administered PFOS (10 mg/kg/day) alone or with Nar (100 mg/kg/day) for 3 weeks. Nar supplementation led to resumption of elevated serum hepatic enzyme activities and increased relative liver weight in PFOS-challenged mice. Moreover, Nar treatment increased hepatic expression of transcription factor NRF2 protein and its regulated antioxidative enzyme genes heme oxygenase‑1, superoxide dismutase and catalase, with an inhibition of malondialdehyde and hydrogen peroxide production. Furthermore, simultaneous administration of Nar suppressed PFOS-induced elevation in NF-κB activity and generation of inflammatory cytokines TNF-α and IL-6 in the liver. In addition, Nar enhanced anti-apoptotic Bcl-2 expression, decreased pro-apoptotic Bax expression and inhibited caspase‑3 activation in liver tissue in mice exposed to PFOS. Our results indicate that Nar protects against PFOS-induced hepatotoxicity in mice via modulating oxidative, inflammatory and apoptotic pathways. •Naringin restored serum hepatic enzyme activities and relative liver weight in PFOS-exposed mice.•Naringin exerted anti-oxidative, anti-inflammatory and anti-apoptotic roles in PFOS-induced hepatic damage.•NRF2 up-regulation and NF-κB inhibition contribute to hepatoprotection against PFOS by naringin.