8种多环芳烃联合暴露致大鼠肝脏毒性及BMDL推导
作者:
作者单位:

1.华中科技大学同济医学院公共卫生学院,食品营养与安全湖北省重点实验室,湖北 武汉 430030;2.国家食品安全风险评估中心,北京 100022

作者简介:

杨淼 男 硕士研究生 研究方向为食品安全风险评估 E-mail:1339277462@qq.com

通讯作者:

毛伟峰 女 副研究员 研究方向为食品安全风险评估 E-mail:maoweifeng@cfsa.net.cn

中图分类号:

R155

基金项目:

国家自然科学基金(81803241)


Hepatotoxicity and BMDL derivation in rats under combined exposure to eight kinds of polycyclic aromatic hydrocarbons
Author:
Affiliation:

1.School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hubei Key Laboratory of Food Nutrition and Safety, Huazhong University of Science and Technology,Hubei Wuhan 430030, China;2.China National Center for Food Safety Risk Assessment, Beijing 100022, China

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    摘要:

    目的 探究8种多环芳烃(PAH8)联合暴露的大鼠肝脏毒性,利用基准剂量法(BMD)获得PAH8致肝脏毒性的基准剂量95%置信区间下限值(BMDL)。方法 雄性SD大鼠随机分为5组,每组10只,分别按照0、10、50、250和1 000 μg/kg·BW剂量的PAH8连续染毒30 d后处死大鼠,计算脏器系数,进行肝脏病理学检测和油红O染色,检测血清谷丙转氨酶、谷草转氨酶、丙二醛、谷胱甘肽过氧化物酶(GSH-Px)、甘油三酯(TG)、总胆固醇(TC)的水平及肝脏TG、TC含量。选择具有统计学意义、毒理学意义和剂量效应趋势的肝脏毒性数据,利用BMDS 3.2软件进行BMD分析,选择最佳拟合模型得到BMDL值。结果 1 000 μg/kg·BW剂量组大鼠肝脏系数较对照组显著升高(P<0.05)。PAH8染毒后部分大鼠肝脏出现细胞水肿、炎性浸润、脂肪变性等病理改变。10~250 μg/kg·BW剂量组血清GSH-Px较对照组显著升高(P<0.01),但1 000 μg/kg·BW剂量组GSH-Px显著降低(P<0.001)。肝脏中TC含量呈现剂量效应趋势,1 000 μg/kg·BW剂量组较对照组显著升高(P<0.001)。其他指标与对照组相比均无显著性差异(P>0.05)。利用肝脏TC含量进行BMD分析,选择Hill模型得到PAH8致大鼠肝脏毒性的BMDL和BMD分别为47.61和213.52 μg/kg·BW。根据肝脏TC含量得到PAH8的未观察到有害作用水平(NOAEL)和观察到有害作用的最低水平(LOAEL)分别为250和1 000 μg/kg·BW。结论 PAH8联合暴露引起肝脏脂质异常蓄积,致大鼠肝脏毒性的BMDL为47.61 μg/kg·BW,低于相应的NOAEL/LOAEL值。

    Abstract:

    Objective To investigate the hepatotoxicity induced by the combined exposure of eight types of PAHs (PAH8) in rats, the lower limit of the 95% confidence interval of benchmark dose (BMDL) of PAH8-induced hepatotoxicity was determined using the benchmark dose (BMD) method.Methods Male SD rats were randomly divided into five groups (10 rats in each group) and were exposed to PAH8 at doses of 0, 10, 50, 250, and 1 000 μg/kg·BW, respectively. Rats were sacrificed after 30 d, and organ coefficients were calculated. Liver pathological examination and oil-red O staining were performed. Serum alanine aminotransferase, aspartate aminotransferase, malondialdehyde, glutathione peroxidase (GSH-Px), triglyceride (TG), total cholesterol (TC) levels, and liver TG and TC levels were measured. Hepatotoxicity data with statistical significance, toxicological significance, and dose-effect trend were selected. BMD analysis was performed using the BMDS 3.2 software. BMDL values of PAH8-induced hepatotoxicity in rats were obtained by choosing the optimal fitting model.Results The liver coefficient of the 1 000 μg/kg·BW group was significantly higher than that in the control group (P<0.05). After PAH8 exposure, some rats showed pathological changes, such as cell edema, inflammatory infiltration, and liver steatosis. Serum GSH-Px in the 10-250 μg/kg·BW group was significantly higher than that in the control group (P<0.01) but significantly decreased in the 1 000 μg/kg·BW group (P<0.001). The TC content in the liver showed a dose-dependent trend and increased significantly in the 1 000 μg/kg·BW group (P<0.001). No significant changes in other indexes were observed compared with the control group (P>0.05). Liver TC content was used for BMD analysis, and the BMDL and BMD of PAH8 based on the Hill model were 47.61 and 213.52 μg/kg·BW, respectively. The non-observed adverse effect level and lowest observed adverse effect level of PAH8 were 250 and 1 000 μg/kg·BW, respectively.Conclusion Combined exposure to PAH8 caused abnormal lipid accumulation in the liver, and the BMDL value of liver toxicity in PAH8 rats was 47.61 μg/kg·BW, which was lower than the NOAEL/LOAEL.

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杨淼,卢宇翾,曹鑫,毛侃敏,毛伟峰,郝丽萍.8种多环芳烃联合暴露致大鼠肝脏毒性及BMDL推导[J].中国食品卫生杂志,2023,35(6):813-819.

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  • 收稿日期:2022-10-06
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  • 在线发布日期: 2023-09-25
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