Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA.
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA.
Environ Toxicol Pharmacol. 2023 Jun;100:104148. doi: 10.1016/j.etap.2023.104148. Epub 2023 May 13.
Mancozeb is a widely-used, broad-spectrum contact dithiocarbamate fungicide. Dithiocarbamates are known to trans-chelate metals. This study was designed to evaluate the potential of Mancozeb to mobilize and bioaccumulate essential trace metals in various tissues. Long-Evans rats were orally gavaged with 0, 50, or 100 mg/kg/day of Mancozeb for 28 days. Mancozeb caused a significant increase in copper and manganese in the hippocampus and manganese in the liver. Exceedingly higher level of copper was detected in the renal cortex using ICP-OES in both dose groups. This was confirmed histologically in the tubular epithelial cells. In addition, copper-associated protein levels were also increased. Copper bioaccumulation in the renal cortex was accompanied by oxidative damage and tubular insult indicated by increased 4-HNE, KIM-1, and NGAL immunoreactivity. These findings demonstrate that low-dose Mancozeb exposure is a potential risk for kidney injury due to copper overload and warrants further in vivo and human population-based investigations.
代森锰锌是一种广泛使用的、广谱的接触型二硫代氨基甲酸盐类杀菌剂。二硫代氨基甲酸盐类物质已知可进行金属转螯合作用。本研究旨在评估代森锰锌在各种组织中动员和生物累积必需痕量金属的潜力。长爪沙鼠经口灌胃给予 0、50 或 100mg/kg/天的代森锰锌，共 28 天。代森锰锌导致海马体中的铜和锰以及肝脏中的锰显著增加。使用 ICP-OES 在两个剂量组中均检测到肾皮质中铜的含量极高。这在管状上皮细胞的组织学上得到了证实。此外，铜相关蛋白的水平也增加了。肾皮质中的铜生物累积伴随着氧化损伤和管状损伤，表现为 4-HNE、KIM-1 和 NGAL 免疫反应性增加。这些发现表明，低剂量代森锰锌暴露可能会导致铜过载引起的肾脏损伤，这需要进一步进行体内和人群为基础的研究。
