RESUMO
We have studied the prophylactic effect of new derivatives of ursodeoxycholic acid (UDCA), including UDCA-N-acetylcysteine, UDCA-L-acetylcysteine, and nor-UDCA (in doses equivalent to 40 mg/kg of UDCA) on the development of experimental alcoholic steatohepatitis induced by the Lieber-DeCarli liquid ethanol-containing diet. Results demonstrated that most of the investigated compounds produced a hepatoprotective effect, improving biochemical tests and liver morphology, as manifested by decreasing steatosis intensity, activity of alkaline phosphatase and gamma-glutamyltranspeptidase, triglyceride level in blood serum and liver, and TNF alpha content. However, nor-UDCA was most effective as compared to UDCA in preventing the accumulation of triglycerides in the liver.
Assuntos
Colagogos e Coleréticos/farmacologia , Fígado Gorduroso Alcoólico/prevenção & controle , Fígado/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ácido Ursodesoxicólico/análogos & derivados , Ácido Ursodesoxicólico/farmacologia , Acetilcisteína/química , Fosfatase Alcalina/metabolismo , Animais , Dieta , Etanol , Fígado Gorduroso Alcoólico/tratamento farmacológico , Fígado Gorduroso Alcoólico/metabolismo , Fígado Gorduroso Alcoólico/patologia , Feminino , Fígado/metabolismo , Ratos , Ratos Wistar , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfa/sangue , gama-Glutamiltransferase/metabolismoRESUMO
The effect of infliximab (1 and 10 mg/kg, i.p., during 10 days) on alcoholic steatohepatitis has been studied in rats fed with ethanol-containing liquid diet over 10 weeks. Both doses of infliximab showed immunomodulatory and anti-inflammatory effects, whereas only the maximum drug dose significantly decreased lipid accumulation in the liver. It can be concluded that infliximab (10 mg/kg) acts as an effective hepatoprotector, anti-inflammatory agent, and immunomodulator in rats with experimental alcoholic steatohepatitis.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Anticorpos Monoclonais/farmacologia , Fígado Gorduroso Alcoólico/tratamento farmacológico , Fatores Imunológicos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Animais , Depressores do Sistema Nervoso Central/efeitos adversos , Depressores do Sistema Nervoso Central/farmacologia , Modelos Animais de Doenças , Etanol/efeitos adversos , Etanol/farmacologia , Fígado Gorduroso Alcoólico/sangue , Fígado Gorduroso Alcoólico/etiologia , Feminino , Infliximab , Ratos , Ratos WistarRESUMO
Alimentary obesity induced by the long-term feeding of rats by high-fat diet results the reducing of rate and efficiency of oxidative phosphorylation in liver mitochondria when NAD-dependent substrates are used. The treatment of the obese rats with panthotenic acid derivatives (phosphopantotenate, panthetin, panthenol) enhanced oxidative phosphorylation of pyruvate and fatty acid carnitine esters. Among investigated compounds panthenol activated respiratory control and phosphorylation rate more effectively. Moreover, panthenol, but not phosphopanthotenate nor panthetine, increased the activity of carnitine palmitoyltransferase 1 that confirms the preferable usage of fatty acids for mitochondrial oxidation under the influence of this compound.
Assuntos
Mitocôndrias Hepáticas/metabolismo , Obesidade/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Ácido Pantotênico/administração & dosagem , Animais , Carnitina/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Ácidos Graxos/metabolismo , Feminino , Obesidade/patologia , Oxirredução , Ácido Pantotênico/análogos & derivados , Ácido Pirúvico/metabolismo , RatosRESUMO
It has been found that hydroxylated pyrimidine derivatives actively participate in metabolic proceeds related to functioning of vitamin B1-dependent enzymes (transketolase, 2-oxo acid dehydrogenase). Hydroxypyrimidines also induce a significant increase in the levels of total lipids and cholesterol in the mice liver, not changing the phospholipid content.
