The Ameliorative Effects of Naringin on Cisplatin-Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells

Abstract

In this study, our aim was to investigate the potential therapeutic effects of different doses of naringin on SH-SY5Y neuroblastoma cells by effecting the 3 different cellular processes: (i) apoptosis, (ii) inflammation, and (iii) oxidative stress. For this reason, we performed ELISA to detect the levels/positivity of IL-1-beta, IL-6, IL-10, TGF-beta, SOD, CAT, LPO, VEGF, caspase-3 and caspase-9. Our study was designed as groups in which control, only cisplatin, only naringin and cisplatin with naringin co-incubated groups. In cisplatin and naringin co-incubated groups, cisplatin was applied on SH-SY5Y neuroblastoma cells for 2 h and then co-incubated with appropriate doses of naringin. In the without cisplatin groups, only naringin was administered. CVDK-8 was used for cell viability and FDA-PI immunofluorescent dyes were used to determine the ratio of dead and viable cells. For ELISA; the culture media of all experimental groups were collected and the levels of TGF-beta, IL-10, IL-6 and IL-1-beta, caspase-3, caspase-9, VEGF, SOD, CAT and LPO were determined. Immunofluorescence staining results were also in line with the viability analysis results and neurotoxicity was inhibited at the best 25 µM dose. When the ELISA results are examined, it was seen that Cisplatin caused an important increase in the levels of pro-inflammatory cytokines, caspase-3, caspase-9, and the activities of SOD, CAT, LPO enzymes, while naringin application reduced the levels of mentioned parameters in different doses. Naringin was able to balance the activities of oxidative and anti-oxidant enzymes, suppress inflammation, apoptosis and metastasis. Although it has various beneficial effects on neurotoxicity models, further molecular studies should be performed for better understanding the mechanism of naringin effects.