Comparison of the cytotoxic, nephrotoxic and ototoxic effects of cisplatin and lipoplatin in in vivo neuroblastom tumor model

Aim: The aim of this study was to compare the cytotoxic, cytostatic, ototoxic and nephrotoxic effects of lipoplatin (LIPO) administration according to cisplatin (CDDP) application in the subcutaneous xenograft nude mouse neuroblastoma tumor model. Method: In this experimentally planned study, C1300 neuroblastoma cells were given subcutaneously to 21 male nude mice, weighted 20 gram. When the tumor reached 150 mm3 diameter, 20 mg / kg of saline to the control group, 20 mg / kg of cisplatin and 20 mg / kg of LIPO were given intraperitoneally. The auditory function tests were performed before the agents were given (basal) and after 72 hours of administration. At 72nd hours, the animals were sacrificed and the tumor and cochlea were removed. Creatinine was evaluated in urine samples. In paraffin-embedded tissue samples, apoptosis and necrosis (TUNEL) and anti-oxidant and anti-inflammatory related protein levels (COX2, SOD2 and INOS) were determined by immunohistochemistry. The data were compared between the groups with SPSS 22.0 version. P value less than 0.05 is considered significant. Results: Apoptosis and necrosis rates were higher in the LIPO group than in CDDP (p = 0.035 and p = 0.010). In the spiral ganglion, apoptosis and necrosis were lower in the LIPO group than in CDDP (p = 0.002 and p = 0.002). COX2 pattern in the cochlea was positive in both control and LIPO group and negative in CDDP (p = 0.001). SOD2 and INOS2 showed no difference between groups (p> 0.05). The auditory functions are similar in baseline values and have a better threshold value in the LIPO group than CDDP. Conclusion: In the treatment of neuroblastoma, the use of LIPO seems to be beneficial to eliminate the dose-limiting side effects of CDDP. In addition, LIPO has a higher anti-tumor effect than CDDP. In further studies, it is recommended that the mechanism of these superior properties of LIPO should be evaluated within the tumor microenvironment. Keywords: Neuroblastoma, Lipoplatin, Cisplatin, Ototoxicity, Cytotoxicity