Pavlovic V, Cekic S, Kamenov B, Ciric M, Krtinic D
Institute of Physiology, Medical Faculty University of Nis, Serbia.
Pediatric Clinic, University Clinical Centre, Nis, Serbia.
Folia Biol (Praha). 2015;61(3):116-23. doi: 10.14712/fb2015061030116.
Mancozeb, as a dithiocarbamate fungicide, has been found to exhibit toxicological manifestations in different cells, mainly by generation of free radicals which may alter antioxidant defence systems in cells. The effect of mancozeb on the cells of a primary lymphoid organ has not been studied. In the present study, the effects of mancozeb (0.2, 2 and 5 μg/ml) or mancozeb+ascorbic acid (100 μg/ml), or ascorbic acid alone or control medium alone on the levels of cell viability, apoptosis, intracellular reactive oxygen species production (ROS), mitochondrial membrane potential (MMP) and ATP levels in rat thymocytes were examined in vitro. Cells treated with mancozeb displayed a concentration-dependent increase of hypodiploid cells and ROS production followed by markedly decreased viability of the cells, MMP and ATP levels. Application of ascorbic acid significantly reduced cytotoxicity in cell cultures treated with 0.2 and 2 μg/ml of mancozeb, together with significantly decreased ROS levels and increased MMP and ATP levels. In cells treated with 5 μg/ml of mancozeb, ascorbic acid failed to reduce toxicity while simultaneously increasing the apoptosis rate of thymocytes. These results suggest that ROS plays a significant role in mancozeb-induced toxicity, through alteration of mitochondrial function. Ascorbic acid administration reduced the toxicity rate in cells treated with lower mancozeb concentrations, while it may have the ability to shift cells from necrosis to apoptosis in the presence of highest mancozeb concentrations.
代森锰锌作为一种二硫代氨基甲酸盐类杀菌剂，已被发现会在不同细胞中表现出毒理学特征，主要是通过产生自由基，这些自由基可能会改变细胞中的抗氧化防御系统。代森锰锌对初级淋巴器官细胞的影响尚未得到研究。在本研究中，体外检测了代森锰锌（0.2、2和5μg/ml）或代森锰锌+抗坏血酸（100μg/ml）、单独的抗坏血酸或单独的对照培养基对大鼠胸腺细胞的细胞活力、凋亡、细胞内活性氧产生（ROS）、线粒体膜电位（MMP）和ATP水平的影响。用代森锰锌处理的细胞显示亚二倍体细胞和ROS产生呈浓度依赖性增加，随后细胞活力、MMP和ATP水平显著降低。抗坏血酸的应用显著降低了用0.2和2μg/ml代森锰锌处理的细胞培养物中的细胞毒性，同时显著降低了ROS水平，提高了MMP和ATP水平。在用5μg/ml代森锰锌处理的细胞中，抗坏血酸未能降低毒性，同时增加了胸腺细胞的凋亡率。这些结果表明，ROS通过改变线粒体功能在代森锰锌诱导的毒性中起重要作用。给予抗坏血酸降低了用较低浓度代森锰锌处理的细胞中的毒性率，而在存在最高浓度代森锰锌的情况下，它可能有能力使细胞从坏死转变为凋亡。
