Hepatoprotective effects of rolipram on experimental murine model of immune-mediated fulminant hepatitis
Assiut Medical Journal. 2009; 33 (3): 11-22
em En
| IMEMR
| ID: emr-135410
Biblioteca responsável:
EMRO
ABSTRACT
Autoimmune fulminant hepatic failure has a specific clinical and social importance. However, it still lacks its effective and targeting medication. Herein, we investigated the influence of rolipram, a selective PDE-IV inhibitor, on D-galactosamine/lipopolysaccharide [DGalN/ LPS]-induced immune-mediated and dose-dependent fulminant hepatitis and acute lethality in mice; in which tumor necrosis factor-alpha [TNF-alpha] plays a pivotal role. Two complementary sets of experiments were conducted in this work. Firstly, we assessed the distinct hepatoprotective effects of rolipram on this model. After an intraperitoneal [i.p.] injection of a single sub-lethal dose of D-GalN/LPS [0.2 mg/g + 5 microg/g] into mice a serious destructive hepatic injury was developed over a period of 4 days, and it was associated with abundant increases in the serum levels of liver enzymes [AST and ALT] and the concentrations of TNF-alpha in serum and hepatic tissues, as well as an over-production of vascular cellular adhesion mlocule-1 [VCAM-1] on liver tissues. Additionally, the histopathological findings showed the features of severely injured liver. Interestingly, treatment with rolipram [3 mg/kg, i.p.; at days +0, +1, +2, and +3] remarkably reversed all the aforementioned biochemical, immunological, and histopathological hallmarks of D-GalN/ LPS-induced hepatitis. Secondly, the prophylactic administration of rolipram [10 mg/kg, i.p.; at -24, -12, and -1 h] efficiently prevented the severe acute deaths and massive systemic TNF-alpha production that induced by a lethal dose of D-GalN/LPS [0.6 mg/g + 15 microg/g; i.p.] over 24-h period. The results reveal that rolipram; via, at least in part, inhibition of TNF-alpha production and VCAM-1 over-expression, has obvious hepatoprotective effects on D-GalN/LPS-induced lethal destructive hepatitis in mice. In addition, the beneficial role of rolipram in suppressing the progression of human hepatitis in which TNF-alpha is markedly involved could be considered
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Índice:
IMEMR
Assunto principal:
Molécula 1 de Adesão de Célula Vascular
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Substâncias Protetoras
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Rolipram
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Fatores de Necrose Tumoral
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Histologia
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Fígado
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Testes de Função Hepática
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Camundongos
Limite:
Animals
Idioma:
En
Revista:
Assiut Med. J.
Ano de publicação:
2009