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J Pharmacol Exp Ther ; 361(2): 292-302, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28209723

RESUMO

Background: Mitochondrion is an important metabolic and energetic organelle that regulates several cellular processes. Mitochondrial dysfunction has been related to liver diseases including hepatocellular carcinoma. As a result, the energetic demand is not properly supplied and mitochondrial morphologic changes have been observed, resulting in an altered metabolism. We previously demonstrated the chemopreventive effect of the hepatoprotector IFC-305. Aim: In this work we aimed to evaluate the functional, metabolic, and dynamic mitochondrial alterations in the sequential model of cirrhosis-hepatocellular carcinoma induced by diethylnitrosamine in rats and the possible beneficial effect of IFC-305. Methods: Experimental groups of rats were formed to induce cirrhosis-hepatocellular carcinoma and to assess the IFC-305 effect during cancer development and progression through the evaluation of functional, metabolic, and dynamic mitochondrial parameters. Results: In this experimental model, dysfunctional mitochondria were observed and suspension of the diethylnitrosamine treatment was not enough to restore them. Administration of IFC-305 maintained and restored the mitochondrial function and regulated parameters implicated in metabolism as well as the mitochondrial dynamics modified by diethylnitrosamine intoxication. Conclusion: This study supports IFC-305 as a potential hepatocellular carcinoma treatment or as an adjuvant in chemotherapy.


Assuntos
Adenosina/análogos & derivados , Anticarcinógenos/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Cirrose Hepática Experimental/prevenção & controle , Neoplasias Hepáticas Experimentais/prevenção & controle , Mitocôndrias Hepáticas/efeitos dos fármacos , Adenosina/farmacologia , Adenosina/uso terapêutico , Trifosfato de Adenosina/biossíntese , Animais , Anticarcinógenos/farmacologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Complexo I de Transporte de Elétrons/metabolismo , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Potencial da Membrana Mitocondrial , Mitocôndrias Hepáticas/metabolismo , Ratos Wistar
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