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Dig Dis Sci ; 65(1): 215-224, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31312992

RESUMO

BACKGROUND: A significant role in pathogenesis of cholangitis is attributed to excessive reactive oxygen species production and oxidative stress. Therefore, antioxidants could be promising therapeutics. AIMS: The effects of powerful free radical scavenger C60 fullerene on hepatic and pancreatic manifestations of acute and chronic cholangitis in rats were aimed to be discovered. METHODS: Acute (AC, 3 days) and chronic (CC, 28 days) cholangitis models were simulated by single (AC) and 4 weekly (CC) α-naphthylisothiocyanate per os administrations. Pristine C60 fullerene aqueous colloid solution (C60FAS, 0.15 mg/ml, size of aggregates 1.2-100 nm) was administered either per os or intraperitoneally at a dose of 0.5 mg/kg C60 fullerene daily (AC) and every other day (CC). Prednisolone was used as a reference. Liver and pancreas autopsies were analyzed, and blood serum biochemical markers were measured. Pan-cytokeratin expression in HepG2 cells was assessed after 48-h incubation with C60FAS. RESULTS: On AC, C60FAS normalized elevated bilirubin, alkaline phosphatase, and triglycerides, diminished fibrotic alterations in liver, and improved pancreas state when applied by both ways. Additionally, C60FAS per os significantly reduced the signs of inflammation in liver and pancreas. On CC, C60FAS also mitigated liver fibrosis and inflammation, improved pancreas state, and normalized alkaline phosphatase and triglycerides. The remedy effect of C60FAS was more expressed compared to that of prednisolone on both models. Furthermore, C60FAS inhibited pan-cytokeratin expression in HepG2 cells in a dose-dependent manner. CONCLUSION: Pristine C60 fullerene inhibits liver inflammation and fibrogenesis and partially improved liver and pancreas state under acute and chronic cholangitis.


Assuntos
Anti-Inflamatórios/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Colangite/tratamento farmacológico , Fulerenos/farmacologia , Cirrose Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Pancreatopatias/prevenção & controle , 1-Naftilisotiocianato , Animais , Biomarcadores/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Colangite/sangue , Colangite/induzido quimicamente , Colangite/patologia , Modelos Animais de Doenças , Sequestradores de Radicais Livres/farmacologia , Células Hep G2 , Humanos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/sangue , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatopatias/sangue , Pancreatopatias/induzido quimicamente , Pancreatopatias/patologia , Prednisolona/farmacologia , Ratos Wistar , Fatores de Tempo
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