Doxorubicin-induced neurotoxicity differently affects the hippocampal formation subregions in adult mice

• DOI: 10.1016/j.heliyon.2024.e31608
• Publication Date: 2024-05-24T06:49:54Z
• Authors: Ana Dias-Carvalho; Mariana Ferreira; Ana Reis-Mendes; Rita Ferreira; Maria de Lourdes ...; Eduarda Fernandes; Susana Isabel Sá; João Paulo Capela; Félix Carvalho; Vera Marisa Costa
• Keywords: Neurotoxicity

Doxorubicin (DOX) is an anthracycline used to treat a wide range of tumours. Despite its effectiveness, it associated with long adverse effects, which cognitive deficits stand out. The present study aimed assess the neurologic outcome pathways two clinically relevant cumulative doses DOX. Adult male CD-1 mice received biweekly intraperitoneal administrations for 3 weeks until reaching 9 mg/kg (DOX9) or 18 (DOX18). Animals were euthanized one week after last administration, and biomarkers oxidative stress brain metabolism evaluated in whole brain. Coronal sections fixed brains specific determinations prefrontal cortex (PFC) hippocampal formation (HF). In brain, DOX18 tended disrupt antioxidant defences, affecting glutathione levels manganese superoxide dismutase expression. Considering regional analysis, increased volume all areas evaluated, while GFAP-immunoreactive astrocytes decreased dentate gyrus (DG) CA3 region HF, both dose-dependent manner. Concerning apoptosis pathway, whereas Bax DOX9 group, group. Only latter group did Bcl-2 also decrease. While p53 only AIF PFC DG DOX18. Finally, phosphorylation Tau highest DOX dose CA3, TNF-α CA1 Our results indicate new not yet described that could be responsible impairments observed treated patients.