Evaluating the dopaminergic neurotoxic effects of chemotherapeutics

Abstract

Chemotherapy-induced neurotoxicity is one of the most common contraindication seen in the cancer survivors. Thus chemotherapy-induced neurotoxicity can adversely affect the clinical management of these patients. Cancer survivors during chemotherapy often complain about problems with memory retrieval, learning and concentration, which may persevere even post-treatment or never fully resolve. Role of chemotherapeutics in hippocampal neurotoxicity is well established and is referred to as chemobrain or chemofog. However, there are very few reports on the chemotherapeutics-induced neurotoxicity in movement disorders like Parkinson’s disease. Hence, in this study we used dopaminergic cell lines (N27) to investigate the cytotoxic effects of doxorubicin and cyclophosphamide. N27 cells have been well established in studies of dopamine biosynthesis, neurotoxicity and used as a dopaminergic model for in vitro studies. In this study the dopaminergic neurotoxicity was evaluated in N27 cells using MTT assay. The effect of doxorubicin and cyclophosphamide were studied on markers of oxidative stress, mitochondrial functions and other relevant neurotoxic mechanisms. All statistical analyses were performed using the Prism-V software (La Jolla, CA, USA). All data were expressed as Mean ± SEM. Statistical analyses were performed using one-way analysis of variance (ANOVA) followed by an appropriate post-hoc test including Tukey's and Dunnett's method ((p < 0.05) was considered to indicate statistical significance). Doxorubicin significantly induced dopaminergic neurotoxicity. Thus, if careful patient care measures are not taken with cancer survivors exposed to doxorubicin and cyclophosphamide, it can considerably increase the risk for several movement disorders.