INTRODUCTION: Chemotherapy-related cognitive impairment (“chemobrain”) is a complex neurological consequence of anticancer treatment, the underlying mechanisms of which remain incompletely understood. Although chemotherapeutic agents are effective in eliminating cancer cells, they frequently also damage healthy brain cells, leading to long-lasting neurological dysfunction. Memory deficits affect over 90% of oncology patients and may persist for up to five years after cessation of treatment.

AIM(S): Despite the clinical relevance of this phenomenon, the existing literature lacks comprehensive comparative analyses that consistently evaluate neurotoxicity, dose-response relationships, and inter-agent differences. To address this gap, the aim of the present study was to directly compare the dose-dependent neurotoxic effects of commonly used chemotherapeutic agents from different pharmacological classes within a unified cell model.

METHOD(S): In this study, neuronal cells were treated with increasing doses of selected chemotherapeutic agents, including 5-fluorouracil, oxaliplatin, methotrexate, and paclitaxel. Neurotoxicity was assessed using biochemical assays. Primary cultures of mouse neuronal cells were employed, as the anti-proliferative nature of chemotherapeutic agents limits the suitability of immortalized cell lines for addressing this research question.

RESULTS: The results revealed pronounced time- and dose-dependent neurotoxicity across the tested chemotherapeutic agents from different pharmacological classes. The analysis encompassed their impact on neuronal cell viability, metabolic activity, and markers of cellular damage.

CONCLUSIONS: Collectively, these findings provide a solid foundation for further investigation into the mechanisms underlying chemotherapy-induced neurotoxicity and for the development of pharmacological strategies aimed at mitigating these adverse effects.

FINANCIAL SUPPORT: NCN Preludium 22 Grant no. 2023/49/N/NZ7/03640