Effects of diazepam on Mycobacterium bovis-induced infection in hamsters

The in utero exposure of hamsters to low doses of diazepam results in impaired host defense against Mycobacterium bovis during adulthood. Delayed developmental immunotoxicity, however, represents a specific situation that might not be general. The present experiment was undertaken to investigate the effects of diazepam on hamster resistance to M. bovis using adult animals. The effects of diazepam treatment on serum cortisol levels were also studied. Adult hamsters (N = 10 for each group) were treated with diazepam (E1 = 1.0, E2 = 2.0 or E3 = 3.0 mg kg-1 day-1 subcutaneously) or with control solution (C) for 30 days. Seven days after the beginning of the treatment, the animals received identical inoculum concentrations of M. bovis. Hamsters treated with the higher (2.0 and 3.0 mg kg-1 day-1) doses of diazepam exhibited: 1) increased granuloma areas in the liver (C = 1.81 + or - 1.39, E2 = 10.29 + or - 4.64 and E3 = 15.80 + or - 4.82) and lung (C = 0.54 + or - 0.55, E2 = 6.28 + or - 3.85 and E3 = 6.31 + + or - 3.56) and 2) increased scores of M. bovis colony-forming units isolated from liver (C = 2.0, E2 = 3.0 and E3 = 3.5), lung (C = 1.0, E2 = 3.0 and E3 = 3.5) and spleen (C = 1.0, E2 = 2.5 and E3 = 4.0). These effects were dose dependent, and were not detected or were less severe in animals treated with the lowest (1.0 mg/kg) dose of diazepam as well as in those of the control group. Furthermore, diazepam treatment (3.0 mg kg-1 day-1 for 30 days) increased (E3 = 71.32 + or - 2.99; N = 10) the serum levels of cortisol compared to control hamsters (C = 22.61 + or - 2.75; N = 10). The present data, that demonstrate an impaired defense against M. bovis in adult hamsters treated with diazepam, were tentatively explained on the basis of a direct and/or indirect action of diazepam on the cytokine network. The effects may be related to stimulation of peripheral benzodiazepine receptor binding sites (PBR) by macrophages and/or lymphocytes, or they may be mediated by PBR stimulation of the adrenals

Avaliaçäo quantitativa da concentraçäo de micobactérias em órgäos e humores de hamster experimentalmente infectados com Mycobacterium bovis, estirpe AN 5 / Quantitative evaluation of mycobacterial concentration in organs and fluids of experimentally infected hamster with Mycobacterium bovis, strain AN 5

Descreve-se a tuberculose desencadeada pela inoculaçäo intraperitoneal de 1,0 mg de Mycobacterium bovis (cepa AN 5) em hamsters através de exames bacteriológicos e histopatológicos, realizados 1, 15, 29 e 45 dias após a infecçäo. A bactéria se multiplicou no baço, rins, fígado e pulmöes dos animais infectados, induzindo a formaçäo de lesöes granulomatosas. Um dia após a infecçäo o baço albergou um maior número de bactérias e 45 dias após a infecçäo houve diferença nas concentraçöes bacterianas apenas entre baço e rim, com um maior número de bactérias para o baço. Foram observadas duas fases de bacteremia e a micobactéria foi cultivada a partir do líquido peritoneal em todas as etapas de experimento. Os animais perderam peso em decorrência da doença e morreram em média 50,6 dias após a infecçäo