Identification of hepatotoxicity and renal dysfunction of pyrene in adult male rats
Identification of hepatotoxicity and renal dysfunction of pyrene in adult male rats
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DOI：
10.1002/tox.22638
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发表时间：
2018-09
影响因子：
4.5
通讯作者：
Jiayin Zhu;Li-yang Zhao;Xiao-Xiao Wang-Xiao;Zhe Shi;Yang Zhang;Gang Wu;Shu-Yun Zhang
中科院分区：
文献类型：
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作者：
Jiayin Zhu;Li-yang Zhao;Xiao-Xiao Wang-Xiao;Zhe Shi;Yang Zhang;Gang Wu;Shu-Yun Zhang
多环芳烃（PAHs）是一类主要由碳质材料不完全燃烧形成的持久性有机污染物，对人体健康产生不利影响。在这项研究中，我们研究了芘（一种由 4 个稠合苯环组成的多环芳烃）是否对大鼠有不良影响。成年雄性 Sprague-Dawly 大鼠每天口服赋形剂（玉米油）或芘，剂量为 375、750、1500 或 2200 mg/kg/天，持续 4 天。结果表明，芘对大鼠造成肝毒性。与对照组相比，芘暴露后相对肝脏重量、血浆丙氨酸氨基转移酶和直接胆红素水平显着增加。在芘暴露的大鼠中还发现肝细胞肿胀和变性以及肝脏总谷胱甘肽（GSH）水平降低。我们进一步观察到，在芘暴露的大鼠中，由组成型雄甾烷受体（CAR）调节的几种肝脏代谢酶（例如 CYP2B1 和 CYP2B2）的 mRNA 水平显着增加。这些结果表明，GSH 水平降低、肝代谢酶基因表达升高和 CAR 激活是芘诱导大鼠肝毒性的重要因素。此外，我们发现芘显着诱导血浆炎症指数，包括白细胞和淋巴细胞计数。我们还观察到，芘暴露会增加大鼠肾脏的相对重量，并扰乱肾功能，导致大鼠尿素和肌酐水平升高。
Polycyclic aromatic hydrocarbons (PAHs) are a group of persistent organic pollutants primarily formed from the incomplete combustion of carbonaceous materials, and have adverse effects on human health. In this study, we investigated whether pyrene, a PAH consisting of 4 fused benzene rings, has adverse effects on rat. Adult male Sprague‐Dawly rats were treated daily by oral gavage with vehicle (corn oil) or pyrene at doses of 375, 750, 1500, or 2200 mg/kg/day for 4 days. The results showed that pyrene caused hepatotoxicity in rats. When compared with the control group, relative liver weights, plasma alanine aminotransferase, and direct bilirubin levels significantly increased after pyrene exposure. Hepatocyte swelling and degeneration and decreased hepatic total glutathione (GSH) levels were also found in pyrene‐exposed rats. We further observed that mRNA levels of several hepatic metabolizing enzymes regulated by constitutive androstane receptor (CAR) such as CYP2B1 and CYP2B2 significantly increased in pyrene‐exposed rats. These results suggest that decreased GSH levels, elevated hepatic metabolizing enzyme gene expression, and CAR activation are important contributors for pyrene‐induced hepatotoxicity in rats. Additionally, we found pyrene significantly induced plasma inflammatory indices including white blood cell and lymphocyte counts. We also observed that pyrene exposure increased relative weight of kidneys and disrupted kidney function with elevated urea and creatinine levels in rats.