RESUMO
Staphylococcus (S.) aureus is a major udder pathogen causing bovine mastitis. Some pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), enhance extracellular and intracellular growth of S. aureus, indicating that the inflammatory process favors S. aureus infection. Helenalin is a sesquiterpene lactone with potent anti-inflammatory properties. This study was designed to evaluate the effects of helenalin on S. aureus infection. First, in vitro experiments were conducted. These studies revealed that proliferation of S. aureus in bovine mammary epithelial MAC-T cells treated in the presence or absence of TNF-alpha was markedly reduced in the presence of helenalin. Secondly, in vivo effects of helenalin were investigated. Lactating mice treated in the presence or absence of helenalin were challenged by the intramammary route with S. aureus and the bacteria in the mammary glands were counted 12 h after infection. Significantly less numbers of bacteria were recovered from the infected glands of helenalin-treated mice compared with untreated mice. Moreover, histological examination of mammary tissue from helenalin-treated mice that were challenged with S. aureus indicated that helenalin is able to significantly reduce leukocyte infiltration in the mammary gland following S. aureus inoculation. Our results show that helenalin reduces S. aureus intracellular growth and experimental S. aureus infection. We conclude that helenalin may be of potential interest in the treatment of S. aureus-induced mastitis in the bovine species.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Mastite Bovina/prevenção & controle , Sesquiterpenos/farmacologia , Infecções Estafilocócicas/veterinária , Staphylococcus aureus/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Bovinos , Linhagem Celular , Células Cultivadas , Contagem de Colônia Microbiana/veterinária , Modelos Animais de Doenças , Feminino , Injeções Intraperitoneais , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/microbiologia , Mastite Bovina/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana/veterinária , Sesquiterpenos/administração & dosagem , Sesquiterpenos de Guaiano , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/crescimento & desenvolvimento , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Respiratory alterations induced by an acute exposure to ozone (O(3)) paradoxically resolve during multiday exposure. This adaptation is characteristically accompanied by a gradual attenuation of lung neutrophilia. As maintenance of neutrophilia at the site of inflammation is due to cytokine-mediated delayed neutrophil apoptosis, which is associated with reduced levels of Bax, a proapoptotic protein, we sought to determine whether defects in these mechanisms could account for O(3) adaptation. Lung granulocytes obtained at different time points from calves exposed to 0.75 ppm O(3) for 12 h/d for 7 consecutive days neither showed enhancement of survival nor Bax deficiency, when compared to blood granulocytes. To further investigate the effects of an exogenous oxidative stress on neutrophil survival, human granulocytes were treated with hydrogen peroxide alone, or in combination with granulocyte/macrophage colony-stimulating factor, an antiapoptotic cytokine. Both treatments led to rapid apoptosis associated with downregulation of Bcl-x(L) and Bcl-2, two antiapoptotic proteins. This study shows that O(3) adaptation is associated with a failure in the mechanisms leading to accumulation of neutrophils at the site of inflammation, and suggests that this defect is due to direct proapoptotic effects of exogenous oxidative stress on granulocytes.