Abstract # 2051 Chemobrain in rats – Morphological, oxidative and behavioral effects of doxorubicin administration

Doxorubicin (Dox), a topoisomerase interactive agent, is commonly used to treat several types of cancer. This drug is known to cause cognitive impairments in individuals submitted to long-term chemotherapy (deficits also called as chemobrain). The present study investigated whether morphological, oxidative and behavioral impairments could be induced by Dox. Male Wistar rats were injected with Dox (2.5 mg/kg, once every week for 28 days, intraperitoneal route-IP) or 0.9% saline solution (same volume, IP). During the experimental period, behavioral studies were performed, including the open field test, the elevated plus maze, tests for sociability and preference for social novelty and the novel object recognition task. Brains were analyzed by immunohistochemistry (GFAP or glial fibrillary acidic protein expression in astrocytes) and hematoxylin-eosin and luxol fast blue (for myelin) staining techniques, as well as for the assessment of oxidative parameters (thiobarbituric acid reactive substances-TBARS, catalase, superoxide dismutase-SOD, glutathione peroxidase-GPX, glutathione reductase-GR, nitric oxide-NO). Dox-injected rats presented increased GFAP expression in all analyzed areas (frontal cortex, striatum, hippocampus, hypothalamus, granular and molecular layers of the cerebellum). Dox administration also increased the levels of the oxidative indicators TBARS, NO and GR and caused memory impairments as seen in the novel object recognition test. No signs of demyelination and/or neuronal loss were found. Results suggest that astrogliosis and oxidative stress induced by Dox may be linked to chemotherapy-induced memory deficits.