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

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-1ß, 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.

Depressive behavior induced by unpredictable chronic mild stress increases dentin hypersensitivity in rats.

OBJECTIVE: The present study evaluated the nociceptive response induced by dentin hypersensitivity after dental erosion in rats that were exhibited to unpredictable chronic mild stress (UCMS)-induced depressive-like behavior. DESIGN: Adult male rats were subjected to UCMS (depression [D] group) or not (no depression [ND] group) for 30days and received either acidic solution to induce dental erosion (E) or water (W), thus forming the WND, END, WD, and ED groups. After the end of treatment, depressive-like parameters (i.e., sucrose preference and immobility in the forced swim test) and dentin hypersensitivity were evaluated. Plasma tumor necrosis factor α (TNF-α) and corticosterone levels were measured, and astrocytic glial fibrillary acidic protein (GFAP) expression was evaluated in the prefrontal cortex, hippocampus, amygdala, and hypothalamus. RESULTS: Administration of the acidic solution potentiated dentin hypersensitivity and increased corticosterone levels in the ED group compared with the WD group. TNF-α levels only increased in the WD group. The ED group exhibited an increase in astrocytic GFAP expression in the hypothalamus and prefrontal cortex but decreases in the hippocampus. CONCLUSIONS: These results suggest that UCMS exacerbated the nociceptive response associated with dentin hypersensitivity, concomitant with an increase in plasma corticosterone levels. Hypothalamic and prefrontal cortex astrogliosis in the ED group may be attributable to the increase in corticosterone associated to UCMS procedure. The reduction of astrocytic GFAP expression in the hippocampus in the ED group supports the association between dentin hypersensitivity and depression.

Dosagem de lisozima para avaliação da resposta imune em bezerros

O presente trabalho visou verificar a eficiência da dosagem de lisozima como indicador de imunidade em bovinos, valendo-sede animais naturalmente acometidos de processo diarréico. Para tanto, foram utilizados bezerros com até três meses deidade, criados em manejo semi-intensivo e divididos em três grupos experimentais (I sem diarréia, II com diarréia massem sintomas sistêmicos, III com diarréia e sintomas sistêmicos). Foram colhidas amostras sangüíneas de cada animal,que foram processadas para a realização da dosagem de gamaglobulinas por eletroforese, dosagem de IgG por imunodifusãoradial, contagem de linfócitos e dosagem de lisozima. Os resultados encontrados mostraram existir linfopenia nos animais dogrupo III, mas não foi verificada hipogamaglobulinemia na eletroforese ou na imunodifusão radial. Não foram encontradasdiferenças estatisticamente significantes no nível de lisozima entre os grupos estudados. Não foi possível demonstrar correlaçãoentre a dosagem de lisozima e os outros indicadores preconizados no presente experimento. Todavia, embora nopresente experimento não se tenha encontrado uma correlação positiva entre o teor de lisozima e parâmetros de respostaimunitária, os resultados obtidos sugerem que novos trabalhos devam ser realizados para que tal parâmetro seja validadocomo indicador biológico.