(194) N,N’-bis(2-mercaptoethyl)isophthalamide Protects Human Kidney Proximal Tubule Cells against Cisplatin-induced Nephrotoxicity.

Objective : Cisplatin, an anticancer drug, causes severe nephrotoxicity as a dose-limiting adverse effect. So far, no drug has been approved to prevent cisplatin nephrotoxicity. The objective of our study is to investigate the effects of N,N’-bis(2-mercaptoethyl)isophthalamide (NBMI) against cisplatin-induced toxicity in HK-2 non-cancerous human kidney proximal tubule cells, A2780 ovarian cancer cells, and A549 lung cancer cells. NBMI is a lipophilic, non-toxic thiol compound known to be a metal chelator and an antioxidant.

Methods: To determine the effect of NBMI against cisplatin-induced toxicity, we performed the MTS cell viability assay, the DCF-DA fluorescent dye reactive oxygen species (ROS) assay, the GSH-Glo glutathione assay, and the lactate dehydrogenase (LDH) Glo necrotic cell death assay. We used a ‘pretreatment setup’ involving treating cells with NBMI (10-100 µM) for 24 hours followed by a 24-hour exposure to 25 µM cisplatin.

Results: Cisplatin (0-1000 µM) induced concentration-dependent cytotoxicity in HK-2 cells and the 25 µM concentration was selected for further experiments. NBMI was safe up to 100 µM, and pretreatment with NBMI (10-100 µM) prevented cisplatin-induced cell death. NBMI prevented cisplatin-induced ROS elevation and intracellular glutathione reduction. Cisplatin-induced elevated LDH levels were also prevented by NBMI. Interestingly, NBMI failed to protect A2780 and A549 cancer cells from cisplatin-induced cytotoxicity implying that NBMI does not interfere with the anticancer activity of cisplatin.

Conclusions: Positive findings from this study would present NBMI as a promising chemoprotectant to improve the prognosis and quality of life of cancer patients on cisplatin therapy.