Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
J Agric Food Chem. 2012 Feb 22;60(7):1887-92. doi: 10.1021/jf2052042. Epub 2012 Feb 10.
In the present study, we examined the toxicity of benzyl ITC (BITC) and its urinary mercapturic acid metabolite (BITC-NAC), using a normal renal proximal tubular cell line, pig LLC-PK1. BITC increased cell death with an IC(50) value of about 7 μM, whereas the cytotoxic effect of BITC-NAC was five times weaker than that of BITC. We observed a significant necrosis of the compounds on LLC-PK1 cells with oxidative stress. In the presence of 5 mM glutathione (GSH), comparable to physiological levels, the cytotoxicity of BITC-NAC as well as BITC was significantly reduced. Furthermore, the increase in intracellular GSH levels by pretreatment with NAC before the BITC treatment resulted in inhibition of the BITC-induced necrotic events as well as intracellular oxidative stress. These results suggest that GSH is a determinant of cellular resistance against the BITC-mediated and oxidative stress-dependent cytotoxicity in renal proximal tubular cells.
在本研究中，我们使用正常的肾近端肾小管细胞系猪 LLC-PK1 检查了苄基异硫氰酸酯 (BITC) 及其尿硫代尿酸代谢物 (BITC-NAC) 的毒性。BITC 的细胞死亡 IC50 值约为 7 μM，而 BITC-NAC 的细胞毒性比 BITC 弱五倍。我们观察到化合物对 LLC-PK1 细胞有明显的坏死作用，伴有氧化应激。在 5 mM 谷胱甘肽 (GSH) 的存在下，与生理水平相当，BITC-NAC 以及 BITC 的细胞毒性显著降低。此外，用 NAC 预处理后，细胞内 GSH 水平增加，导致 BITC 诱导的坏死事件以及细胞内氧化应激受到抑制。这些结果表明，GSH 是决定肾近端肾小管细胞对 BITC 介导和氧化应激依赖性细胞毒性的抵抗能力的因素。
