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

Autor:	Dias-Carvalho A; Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal.; UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal., Ferreira M; Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal.; UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal.; LAQV/REQUIMTE, Chemistry Department, University of Aveiro, Aveiro, Portugal., Reis-Mendes A; Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal.; UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal., Ferreira R; LAQV/REQUIMTE, Chemistry Department, University of Aveiro, Aveiro, Portugal., de Lourdes Bastos M; Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal.; UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal., Fernandes E; LAQV/REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal., Sá SI; Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal.; Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Porto, Portugal., Capela JP; Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal.; UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal.; FP-I3ID, Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Porto, Portugal., Carvalho F; Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal.; UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal., Costa VM; Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal.; UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 May 24; Vol. 10 (11), pp. e31608. Date of Electronic Publication: 2024 May 24 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e31608
Abstrakt:	Doxorubicin (DOX) is an anthracycline used to treat a wide range of tumours. Despite its effectiveness, it is associated with a long range of adverse effects, of which cognitive deficits stand out. The present study aimed to assess the neurologic adverse outcome pathways of two clinically relevant cumulative doses of DOX. Adult male CD-1 mice received biweekly intraperitoneal administrations for 3 weeks until reaching cumulative doses of 9 mg/kg (DOX9) or 18 mg/kg (DOX18). Animals were euthanized one week after the last administration, and biomarkers of oxidative stress and brain metabolism were evaluated in the whole brain. Coronal sections of fixed brains were used for specific determinations of the prefrontal cortex (PFC) and hippocampal formation (HF). In the whole brain, DOX18 tended to disrupt the antioxidant defences, affecting glutathione levels and manganese superoxide dismutase expression. Considering the regional analysis, DOX18 increased the volume of all brain areas evaluated, while GFAP-immunoreactive astrocytes decreased in the dentate gyrus (DG) and increased in the CA3 region of HF, both in a dose-dependent manner. Concerning the apoptosis pathway, whereas Bax increased in the DOX9 group, it decreased in the DOX18 group. Only in the latter group did Bcl-2 levels also decrease. While p53 only increased in the CA3 region of the DOX9 group, AIF increased in the PFC and DG of DOX18. Finally, phosphorylation of Tau decreased with the highest DOX dose in DG and CA3, while TNF-α levels increased in CA1 of DOX18. Our results indicate new pathways not yet described that could be responsible for the cognitive impairments observed in treated patients. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vera Marisa Costa is part of Heliyon's Editorial Board. (© 2024 The Authors.)
Databáze:	MEDLINE
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