Kara Mehtap, Oztas Ezgi, Ramazanoğulları Rabia, Kouretas Demetrios, Nepka Charitini, Tsatsakis Aristides M, Veskoukis Aristidis S
Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Istanbul University, 34116, Istanbul, Turkey.
Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500, Larissa, Greece.
Toxicol Rep. 2020 Apr 11;7:501-509. doi: 10.1016/j.toxrep.2020.04.001. eCollection 2020.
Fungicides are used in the agricultural sector against the harmful action of fungi, however they are potential toxic agents for the environment and the living organisms. Benomyl is a widely encountered benzimidazole fungicide that exerts its toxicity via inhibiting microtubule formation in the nervous system and the male reproductive and endocrine systems, whilst it is a known teratogen. Since toxic effects of benomyl and its molecular mechanisms are not fully understood, we aimed to detect its neurotoxic potential via evaluating cytotoxicity, oxidative stress and apoptosis in SH-SY5Y cell line. The cells were incubated with benomyl in a concentration range between 1 and 6 μM for 24 h. Our results indicated a concentration-dependent enhancement of reactive oxygen species measured through flow cytometry and DNA damage evaluated via the comet assay. Additionally, it induced apoptosis in all tested concentrations. According to the findings of the present study, benomyl is a xenobiotic, which it appears to exert its toxic action via a redox-related mechanism that, finally, induces cell apoptosis and death. We believe that this study will offer further insight in the toxicity mechanism of benomyl, although further studies are recommended in order to elucidate these mechanisms in the molecular level.
杀菌剂用于农业领域以对抗真菌的有害作用，然而它们对环境和生物是潜在的有毒物质。苯菌灵是一种广泛使用的苯并咪唑类杀菌剂，它通过抑制神经系统、雄性生殖和内分泌系统中的微管形成来发挥毒性，同时它还是一种已知的致畸剂。由于苯菌灵的毒性作用及其分子机制尚未完全明确，我们旨在通过评估SH-SY5Y细胞系中的细胞毒性、氧化应激和凋亡来检测其神经毒性潜力。将细胞与浓度范围在1至6μM之间的苯菌灵孵育24小时。我们的结果表明，通过流式细胞术测量的活性氧水平呈浓度依赖性增加，通过彗星试验评估的DNA损伤也增加。此外，它在所有测试浓度下均诱导细胞凋亡。根据本研究的结果，苯菌灵是一种外源性物质，它似乎通过一种与氧化还原相关的机制发挥其毒性作用，最终诱导细胞凋亡和死亡。我们相信这项研究将为苯菌灵的毒性机制提供进一步的见解，不过为了在分子水平阐明这些机制，建议进行进一步的研究。
