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

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 oxygenase­1, 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 caspase­3 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.