Facultad de Ciencias Exactas y Naturales, Departamento de Ciencias Marinas, Mar Del Plata, Argentina.
Universidad Nacional de Córdoba - CONICET, Facultad de Ciencias Químicas, Dto. Bioquímica Clínica-CIBICI, Córdoba, Argentina.
Ecotoxicol Environ Saf. 2020 Dec 1;205:111157. doi: 10.1016/j.ecoenv.2020.111157. Epub 2020 Aug 20.
The fungicide carbendazim (CBM) has been applied all around the world but its potential adverse effects other than its recognized activity as endocrine disruptor in non target organisms have been scarcely studied. The aims of this work were (1) to use a battery of biomarkers that can reflect potential negative effects such as oxidative stress, genotoxicity, neurotoxicity or altered immune response; and (2) to examine biomarkers of detoxification by analyzing the gene expression of cytochrome P4501A1 (CYP1A1) and the multi-xenobiotic resistance protein P-glycoprotein (P-gp) in the freshwater fish Jenynsia multidentata exposed to environmentally relevant concentrations of CBM during 24 h. Fish exposed to 5 μg/L showed inhibition of GST activity and an increase of TBARs contents in gills, the organ of direct contact with waterborne contaminants. Genotoxicity - measured in peripheral blood-was evidenced by the increases of micronuclei frequency when fish were exposed to 5, 10 and 100 μg/L CBM and of nuclear abnormalities (NA) frequency at 0.05, 0.5, 5, 10 and 100 μg/L CBM. The expression inhibition of interleukin (IL-1β) and tumor necrosis factor a (TNF-α) at 10, and 5 and 10 μg/L CBM, respectively, indicated an altered immune response. The expression of CYP1A1 was down regulated in liver at 10 μg/L and of P-gp at 5 μg/L CBM, indicating a possible slow on CBM metabolization. On the other hand, in gills CYP1A1 decreased at 5 and 10 μg/L while P-gp was induced at 5 and 100 μg/L CBM. Overall, most of these significant effects were detected below 10 μg/L CBM, in a range of realistic concentrations in aquatic ecosystems worldwide.
杀菌剂多菌灵（CBM）已在全球范围内使用，但除了其作为非靶标生物内分泌干扰物的公认活性外，其潜在的不良影响很少被研究。这项工作的目的是（1）使用一组生物标志物来反映潜在的负面影响，如氧化应激、遗传毒性、神经毒性或改变的免疫反应；（2）通过分析淡水鱼詹尼西亚多齿脂鲤（Jenynsia multidentata）暴露于环境相关浓度的 CBM 24 小时后细胞色素 P4501A1（CYP1A1）和多外源性耐药蛋白 P-糖蛋白（P-gp）的基因表达来检查解毒生物标志物。暴露于 5μg/L 的鱼显示 GST 活性抑制和鳃中 TBARs 含量增加，鳃是与水污染物直接接触的器官。在 5、10 和 100μg/L CBM 暴露时外周血中的遗传毒性增加表明微核频率增加，而在 0.05、0.5、5、10 和 100μg/L CBM 时核异常（NA）频率增加。当鱼分别暴露于 10、5 和 10μg/L CBM 时，白细胞介素（IL-1β）和肿瘤坏死因子 a（TNF-α）的表达抑制表明免疫反应改变。在 10μg/L CBM 时肝中 CYP1A1 的表达下调，在 5μg/L CBM 时 P-gp 的表达下调，表明 CBM 代谢可能减缓。另一方面，在 5 和 10μg/L CBM 时，鳃中的 CYP1A1 减少，而在 5 和 100μg/L CBM 时 P-gp 诱导。总体而言，这些显著影响中的大多数在 10μg/L CBM 以下检测到，在全球水生生态系统中的现实浓度范围内。
