Süloğlu Aysun Kılıç, Karacaoğlu Elif, Koçkaya Evrim Arzu, Selmanoğlu Güldeniz, Loğoglu Elif
Department of Biology, Faculty of Science, Hacettepe University, Beytepe, Ankara, Turkey
Department of Biology, Faculty of Science, Hacettepe University, Beytepe, Ankara, Turkey.
Int J Toxicol. 2014 Jul;33(4):319-324. doi: 10.1177/1091581814530437. Epub 2014 May 6.
The aim of this study was to compare the cytotoxic effects of a newly synthesized thialo benzene derivative 2,4-dithiophenoxy-1-iodo-4-bromobenzene (CHSIBr) and a well-known antifungal agent, fluconazole, in L929 cells. L929 cells were treated with 250, 500, or 1000 µg/mL of CHSIBr and with the same doses of fluconazole. Cytotoxicity tests including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH) leakage, and protein content were compared. Glucose and lactate concentrations were measured to determine alterations in metabolic activity. Apoptosis was investigated by TUNEL test and results were supported with survivin enzyme-linked immunosorbent assay. Treatment with CHSIBr resulted in a concentration-dependent cytotoxicity as indicated by MTT, LDH leakage assay, and decreased protein concentration. The loss of cell viability and the increased LDH leakage in 500 µg/mL and 1000 µg/mL CHSIBr and fluconazole groups indicated cell membrane damage and necrotic cell death. In all groups, metabolic activities were altered but apoptosis was not induced. We have previously investigated lower doses of CHSIBr; there was no cytotoxicity in L929 cells. In this study, higher doses caused cytotoxicity and alterations in metabolic activity . When we consider the similar results obtained from fluconazole and especially the lowest dose of CHSIBr, this newly synthesized compound may be a good alternative antifungal agent.
本研究的目的是比较新合成的噻吩苯衍生物2,4 - 二硫代苯氧基 - 1 - 碘 - 4 - 溴苯（CHSIBr）和一种知名抗真菌剂氟康唑对L929细胞的细胞毒性作用。用250、500或1000μg/mL的CHSIBr以及相同剂量的氟康唑处理L929细胞。比较了包括3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基四氮唑溴盐（MTT）、乳酸脱氢酶（LDH）泄漏和蛋白质含量在内的细胞毒性试验。测量葡萄糖和乳酸浓度以确定代谢活性的变化。通过TUNEL试验研究细胞凋亡，并通过生存素酶联免疫吸附测定法支持结果。MTT、LDH泄漏试验以及蛋白质浓度降低表明，用CHSIBr处理会导致浓度依赖性细胞毒性。500μg/mL和1000μg/mL CHSIBr及氟康唑组中细胞活力的丧失和LDH泄漏增加表明细胞膜受损和坏死性细胞死亡。在所有组中，代谢活性均发生改变，但未诱导细胞凋亡。我们之前研究过较低剂量的CHSIBr；在L929细胞中没有细胞毒性。在本研究中，较高剂量导致细胞毒性和代谢活性改变。当我们考虑从氟康唑以及特别是最低剂量的CHSIBr获得的相似结果时，这种新合成的化合物可能是一种很好的替代抗真菌剂。
