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Am Surg ; 70(9): 797-800, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15481297

RESUMO

Reperfusion after cardiopulmonary bypass causes induction of reactive oxygen species (ROS), elevated plasma levels of bacterial lipopolysaccharide (LPS), and production of tumor necrosis factor-alpha (TNF) by the heart. Nuclear factor-kappaB (NF-kappaB) regulates the expression of TNF. Because NF-kappaB is activated by both LPS and ROS, we hypothesized that an inhibitor of NF-kappaB, pyrrolidine dithiocarbamate (PDTC), would block release of TNF from the heart stimulated by these two agents. With Institutional animal care and use committee (IACUC) approval, rat hearts were perfused Langendorf style. LPS was infused and ROS were generated with a hypoxanthine/xanthine oxidase system. PDTC was added to the perfusion buffer. Other hearts were treated with forskolin in order to elevate cyclic AMP. Timed collections of coronary effluent were made for the determination of coronary flow and measurement of TNF. LPS stimulated TNF release to a maximum of 2247 +/- 133 pg/min at 150 minutes. PDTC inhibited LPS-stimulated TNF release. For instance, at 150 minutes, LPS-stimulated TNF release was 449 +/- 49 pg/min with 100 microM PDTC and was 70 +/- 65 pg/mL with 250 microM PDTC (P < 0.05 vs LPS alone). ROS stimulated TNF release was 1494 +/- 130 pg/min at 150 minutes and was not affected by PDTC. Forskolin almost completely blocked TNF release stimulated by LPS or ROS. These data are consistent with the notion that inhibitors of NF-kappaB block cytokine production stimulated by some agents but not others.


Assuntos
Lipopolissacarídeos/metabolismo , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Animais , Antioxidantes/farmacologia , Quimioterapia do Câncer por Perfusão Regional/métodos , Técnicas In Vitro , Masculino , Modelos Animais , Miocárdio/metabolismo , NF-kappa B/antagonistas & inibidores , Pirrolidinas/farmacologia , Ratos , Ratos Sprague-Dawley , Tiocarbamatos/farmacologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos
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