Naringin protects against perfluorooctane sulfonate-induced liver injury by modulating NRF2 and NF-κB in mice
Naringin protects against perfluorooctane sulfonate-induced liver injury by modulating NRF2 and NF-κB in mice
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柚皮苷通过调节 NRF2 和 NF-κ B 预防小鼠全氟辛烷磺酸诱导的肝损伤
DOI：
10.1016/j.intimp.2018.09.019
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发表时间：
2018-12-01
影响因子：
5.6
通讯作者：
Zhang, Dalei
中科院分区：
文献类型：
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作者：
Lv, Zehui;Wu, Wenyao;Zhang, Dalei
全氟辛烷磺酸 (PFOS) 是一种持久性有机污染物，已被证明会引起多种毒性。在本研究中，我们探讨了柚皮苷（Nar）在减轻PFOS引起的小鼠肝损伤中的作用及其潜在机制。雄性小鼠单独灌胃 PFOS（10 毫克/公斤/天）或与 Nar（100 毫克/公斤/天）一起灌胃 3 周。补充 Nar 可使 PFOS 攻击的小鼠血清肝酶活性恢复升高，并增加相对肝脏重量。此外，Nar处理增加了转录因子NRF2蛋白及其调节的抗氧化酶基因血红素加氧酶-1、超氧化物歧化酶和过氧化氢酶的肝脏表达，并抑制丙二醛和过氧化氢的产生。此外，同时施用 Nar 可抑制 PFOS 诱导的 NF-κ Beta 活性升高以及肝脏中炎症细胞因子 TNF-α 和 IL-6 的产生。此外，Nar 还能增强暴露于 PFOS 的小鼠肝组织中抗凋亡 Bcl-2 的表达，降低促凋亡 Bax 的表达并抑制 caspase-3 的激活。我们的结果表明，Nar 通过调节氧化、炎症和细胞凋亡途径，防止 PFOS 诱导的小鼠肝毒性。
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-kappa Beta activity and generation of inflammatory cytokines TNF-alpha 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.