Protective Effects of Cilastatin against Vancomycin-Induced Nephrotoxicity
Cilastatin protects against vancomycin-induced apoptosis but not necrosis. Proximal tubular epithelial cells (RPTECs) were cultured in the presence of vancomycin (0.6 and/or 3 and 6 mg/mL) and vancomycin plus cilastatin (200 μg/mL) for 24 and/or 48 hours. (a–d) Nuclear staining with DAPI. Adherent RPTECs were stained with DAPI to study if apoptotic-like nuclear morphology was present. Arrows point to fragmented apoptotic nuclei. (e) Quantitative approach to the images presented in (a–d). (f) Oligonucleosomes at 24 hours were quantified in the cell soluble fraction and detected with an ELISA kit. (g) Effect of cilastatin in vancomycin-induced release of LDH. Data are presented as % of total release of LDH obtained by Triton X 100 (TX-100) cell treatment. Data are represented as the mean SEM of at least three separate experiments. versus control and control plus cilastatin, versus the same data without cilastatin, versus the same data without cilastatin.