The protective effect of ondansetron on cisplatin-induced toxicity in neuronal PC12 cells

Background: Sensory peripheral neuropathy and neurotoxicity are a frequent complication resulting from cisplatin (CP)-therapy. The neuroprotective effects of 5-HT3receptor antagonists such as ondansetron (ODT) have indicated in studies. However, little information has been reported on its protective mechanism.Objectives: Therefore, in this study, we have explored the protective effect of ODT on CP-induced toxicity in neuronal PC12 cells. Materials and Methods: The cellular toxicity of CP and ODT on PC12 cell line was investigated by MTT assay after 24h exposure to the drugs. Combined treatment with CP and ODT was performed for evaluation the neuroprotective effect and involved mechanisms of ODT on cytotoxicity-induced by CP on PC12 cell line. The oxidative stress (OS) biomarkers such as malondialdehyde (MDA) concentration, glutathione (GSH) content, and the antioxidative enzymes like superoxide dismutase (SOP) and catalase (CAT) were determined to investigate the toxicity. Finally, caspase-3 levels were measured using ELISA kit. Results: For PC12 cells treated with CP and ODT, the half maximal inhibitory concentration (IC50) value was estimated to be 82.9 ± 7.06 µg/ml and 196.446 ± 7.31 µg/ml, respectively. The combining treatment showed a significant lower cytotoxicity than CP alone. Therefore, ODT could potentially inhibit toxicity and apoptosis through reducing the OS biomarkers and caspase pathway. Conclusion: These results suggest that the application of ODT attenuate the neurotoxicity side effects induced after CP therapy. However, identification of the related mechanisms requires further studies.

Keywords:

Neurotoxicity , 5-HT3 antagonists , Oxidative stress , Malondialdehyde , Caspase pathway