Protective effects of crocin on paclitaxel-induced neurotoxic effects

Paclitaxel is an important chemotherapeutic agent used in different cancer treatments, and its use also causes serious cytotoxic effects on muscle, nervous, liver, and others tissues. Crocin, a natural carotenoid compound, and creates the golden-orange color of saffron (Crocus sativus L.). It is also used in some medical applications such as antitumor, antidepressant, hypotensive, and has a strong antioxidant property. The present study aimed to demonstrate the protective effects of crosin against paclitaxel-induced neurotoxicity. In the present study, cytotoxic effects were determined by cell viability (MTT) and lactate dehydrogenase (LDH) assays in human neuroblastoma cell line (SH-SY5Y). The oxidant/antioxidant status was demonstrated by total antioxidant capacity (TAC) and total oxidative status (TOS). Micronuclei (MN) and Sister Chromatid Exchange (SCE), DNA fragmentation, and caspase 3/7 activities were evaluated. Our results showed that combination treatment of paclitaxel and crocin significantly (p<0.05) ameliorated the cell viability while significantly (p<0.05) reducing LDH release which is sign of cell membrane damage. Crocin significantly (p<0.05) decreased paclitaxel-induced TOS levels while significantly (p<0.05) increasing TAC levels. The increase in DNA fragmentation and the increase in malondialdehyde concentration, the end product of lipid peroxidation, induced by oxidative stress was inhibited. Combination administration of crocin and paclitaxel activated apoptosis via increases in caspase 3/7 expression compared to cisplatin alone. As a result, it was demonstrated that crocin has a significant protective effect against paclitaxel-induced neurotoxicity.