RESUMO
Brazilin, the main constituent of Caesalpinia sappan L., is a natural red pigment that has been reported to possess anti-inflammatory properties. This study aimed to identify a novel anti-inflammatory mechanism of brazilin. We found that brazilin did not cause cytotoxicity below 300 microM, and activated heme oxygenase-1 (HO-1) protein synthesis in a concentration-dependent manner at 10-300 microM in RAW264.7 macrophages without affecting mRNA transcription of HO-1. Additionally, brazilin increased bilirubin production and HO-1 activity in RAW264.7 macrophages. In lipopolysaccharide (LPS)-stimulated macrophages, brazilin suppressed the release of nitric oxide (NO), prostaglandin E(2) (PGE(2)), interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha), and reduced the expression of inducible nitric oxide synthase (iNOS). A specific inhibitor of HO-1, Zn(II) protoporphyrin IX, blocked the suppression of NO production, cytokines release and iNOS expression by brazilin. These results suggest that brazilin possesses anti-inflammatory actions in macrophages and works through a novel mechanism involving the action of HO-1.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Benzopiranos/farmacologia , Heme Oxigenase-1/biossíntese , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Bilirrubina/biossíntese , Caesalpinia , Linhagem Celular , Dinoprostona/biossíntese , Heme Oxigenase-1/antagonistas & inibidores , Interleucina-1beta/biossíntese , Macrófagos/enzimologia , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/biossíntese , Protoporfirinas/farmacologia , RNA Mensageiro/biossíntese , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Median corpuscular fragility of erythrocytes does not differ significantly between fed and fasted Bolivian and Brazilian squirrel monkeys and are similar to values reported in humans and rhesus monkeys. This report further confirms that the fasting hyperbilirubinemia present only in Bolivian squirrel monkeys with a Gilbert-like syndrome is not due to an increased fragility of erythrocytes and should be classified as a nonhemolytic hyperbilirubinemia.
Assuntos
Bilirrubina/biossíntese , Doença de Gilbert/veterinária , Hiperbilirrubinemia/veterinária , Doenças dos Macacos/sangue , Saimiri/sangue , Animais , Bolívia , Brasil , Doença de Gilbert/sangue , Hiperbilirrubinemia/sangue , Masculino , Fragilidade OsmóticaRESUMO
We studied the effect of intravenous zinc protoporphyrin (ZnPP) administration on total body carbon monoxide excretion (VeCO), (an index of heme degradation), blood carboxyhemoglobin level, plasma bilirubin level, and tissue homogenate heme oxygenase activity 24 hours after delivery of rhesus neonates treated at 12 hours of age with heat-damaged erythrocytes (32 mumol heme/kg birth weight). All neonates were delivered by cesarean section and received ampicillin and gentamicin to suppress intestinal flora. The control group (n = 4) was treated with saline solution and ZnPP solvent; the erythrocyte-treated control group (n = 4) received erythrocytes and ZnPP solvent; and two experimental groups received erythrocytes and one dose of 10 (n = 3) or 40 (n = 4) mumol ZnPP/kg body weight, respectively. At 24 hours, administration of erythrocytes alone doubled the VeCO (p less than 0.05), carboxyhemoglobin level, (p less than 0.05), and plasma total bilirubin level (p less than 0.05). Treatment with ZnPP, 40 mumol/kg body weight, caused a significant decrease in VeCO (p less than 0.05), carboxyhemoglobin (p less than 0.05), bilirubin (p less than 0.05), and spleen heme oxygenase (p less than 0.05). Treatment of the erythrocyte-loaded animals with ZnPP, 10 mumol/kg body weight, also significantly (p less than 0.05) lowered VeCO and spleen heme oxygenase activity but did not cause a significant lowering of blood carboxyhemoglobin or plasma bilirubin concentration. We conclude that ZnPP is an effective, dose-dependent in vivo inhibitor of heme oxygenase in the newborn rhesus with latrogenic hemolysis, and that it suppresses both bilirubin production and subsequent accumulation.
Assuntos
Animais Recém-Nascidos/metabolismo , Bilirrubina/biossíntese , Heme Oxigenase (Desciclizante)/antagonistas & inibidores , Icterícia Neonatal/prevenção & controle , Oxigenases de Função Mista/antagonistas & inibidores , Porfirinas/uso terapêutico , Protoporfirinas/uso terapêutico , Animais , Monóxido de Carbono/metabolismo , Eritrócitos , Heme/metabolismo , Hemólise , Humanos , Recém-Nascido , Macaca mulattaRESUMO
Desde sua introduçäo em 1958 a fototerapia tem sido largamente utilizada em neonatologia. Estima-se que cerca de 10 por cento dos recém-nascidos säo submetidos anualmente a fototerapia. Entretanto, apesar do uso frequente e rotineiro, esta terapia ainda e utilizada de maneira empírica e näo controlada na maioria dos serviços. Entre os profissionais de saúde que prestam assistência a recém-nascidos, existe uma crença bastante difundida de que as lâmpadas de fototerapia devem ser substituídas após determinado tempo de uso. Näo existe, entretanto, um consenso quanto ao momento apropriado da substituiçäo. Alguns serviços preconizam a troca após 240 horas de uso, outros com 400, 600 e até 2000 horas de uso. Este estudo, conduz a 2 etapas. Na primeira etapa o objetivo foi determinar o momento ideal para a substituiçäo das lâmpadas fluorescentes baseado no tempo de uso. Numa segunda etapa desta investigaçäo, analisam a situaçäo dos aparelhos de fototerapia utilizados em hospitais públicos do Rio de Janeiro. Determina através da mediçäo periódica da irradiância emitida utilizando-se fotodosimetros especiais. A irradiância emitida por aparelhos de fototerapia de fabricaçäo nacional säo significativamente menores do que as doses terapêuticas recomendadas na literatura.
Assuntos
Recém-Nascido , Bilirrubina/biossíntese , Bilirrubina/fisiologia , Icterícia Neonatal , FototerapiaRESUMO
1. Bilirubin UDP-glucuronyltransferase activity and its dependence on substrate concentrations in rat liver, renal cortex and intestinal mucosa microsomes were studied. 2. Bilirubin monoglucuronide synthesis from unconjugated bilirubin was a higher capacity, lower affinity step in comparison with bilirubin diglucuronide formation in the three tissues tested. 3. Bilirubin glucuronide formation in liver microsomes showed a higher capacity but a lower affinity than extrahepatic ones. Renal cortex and intestinal mucosa exhibited similar kinetics parameters. 4. In vitro bilirubin glucuronidation in renal cortex and intestinal mucosa was quantitatively important as compared with the hepatic one.