Chemobrain in rats: Behavioral, morphological, oxidative and inflammatory effects of doxorubicin administration.

Autor: Cardoso CV; Graduate Program in Environmental and Experimental Pathology, University Paulista, Rua Doutor Bacelar, 1212, 4th Floor, São Paulo (SP), 04026-002, Brazil. Electronic address: vieiramedvet@gmail.com., de Barros MP; Institute of Physical Activity and Sports Science (ICAFE), University Cruzeiro do Sul, Rua Galvão Bueno 868, Building B, 13th Floor, São Paulo (SP), 01506-000, Brazil., Bachi ALL; Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Rua Pedro Ernesto, 240, São José dos Campos (SP), 12245-520, Brazil; Department of Otorhinolaryngology, Federal University of São Paulo, Rua Pedro de Toledo, 947, São Paulo (SP), 04039-002, Brazil., Bernardi MM; Graduate Program in Environmental and Experimental Pathology, University Paulista, Rua Doutor Bacelar, 1212, 4th Floor, São Paulo (SP), 04026-002, Brazil., Kirsten TB; Graduate Program in Environmental and Experimental Pathology, University Paulista, Rua Doutor Bacelar, 1212, 4th Floor, São Paulo (SP), 04026-002, Brazil., de Fátima Monteiro Martins M; School of Veterinary Medicine, University Cruzeiro do Sul, Avenida Tenente Laudelino Ferreira do Amaral, 700, São Paulo (SP), 08060-000, Brazil., Rocha PRD; Graduate Program in Environmental and Experimental Pathology, University Paulista, Rua Doutor Bacelar, 1212, 4th Floor, São Paulo (SP), 04026-002, Brazil., da Silva Rodrigues P; Graduate Program in Environmental and Experimental Pathology, University Paulista, Rua Doutor Bacelar, 1212, 4th Floor, São Paulo (SP), 04026-002, Brazil., Bondan EF; Graduate Program in Environmental and Experimental Pathology, University Paulista, Rua Doutor Bacelar, 1212, 4th Floor, São Paulo (SP), 04026-002, Brazil. Electronic address: bondan@uol.com.br.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2020 Jan 27; Vol. 378, pp. 112233. Date of Electronic Publication: 2019 Sep 12.
DOI: 10.1016/j.bbr.2019.112233
Abstrakt: Doxorubicin (DOX) is known to cause cognitive impairments in patients submitted to long-term chemotherapy (deficits also known as chemobrain). The present study investigated whether DOX administration could affect behavior and brain morphology, as well as oxidative and inflammatory status in rats. Male Wistar rats were injected with DOX (2.5 mg/kg/week, 4 weeks, i.p.) or saline. Behavioral analyses were performed. Brains were collected and analyzed by hematoxylin-eosin and luxol fast blue staining techniques and by immunohistochemistry (for glial fibrillary acidic protein expression in astrocytes; GFAP). Serum and brain levels of TNF-α, IL-1β, IL-6, IL-8, IL-10 and CXCL-1 were determined. Oxidative parameters, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), nitric oxide (NO•), brain iron and ferritin levels, as well as reduced and oxidized glutathione (GSH and GSSG, respectively) and thiobarbituric acid reactive substances (TBARS) were also assessed in brain. DOX-injected rats presented cognitive/memory impairments, increased GFAP expression, increased levels of TBARS, NO and GR, but decreased GSSG and ferritin levels in brain homogenate. In addition, increased serum and brain levels of IL-6, IL-8 and CXCL1 were noted in the DOX group, although IL-10 decreased. As DOX has a poor penetration across the blood-brain barrier (BBB), it is proposed that this drug elicits a systemic proinflammatory response with increase of proinflammatory cytokines which cross the BBB and can be involved in the induction of oxidative molecules and proinflammatory cytokines that altogether induce astrogliosis all over the brain. These events may be responsable for chemotherapy-induced cognitive/memory deficits.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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