title: Functional, Metabolic, and Dynamic Mitochondrial Changes in the Rat Cirrhosis-Hepatocellular Carcinoma Model and the Protective Effect of IFC-305.
abstract: 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.
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (E.C., M.G.L.-R., M.D.-L., G.V.-L., J.R.R.-A., V.C.S.); and Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (C.J.-N., M.T.G.-P.).
authors.forename: Enrique
authors.initials: E
authors.lastname: Chávez
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (E.C., M.G.L.-R., M.D.-L., G.V.-L., J.R.R.-A., V.C.S.); and Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (C.J.-N., M.T.G.-P.).
authors.forename: María Guadalupe
authors.initials: MG
authors.lastname: Lozano-Rosas
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (E.C., M.G.L.-R., M.D.-L., G.V.-L., J.R.R.-A., V.C.S.); and Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (C.J.-N., M.T.G.-P.).
authors.forename: Mariana
authors.initials: M
authors.lastname: Domínguez-López
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (E.C., M.G.L.-R., M.D.-L., G.V.-L., J.R.R.-A., V.C.S.); and Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (C.J.-N., M.T.G.-P.).
authors.forename: Gabriela
authors.initials: G
authors.lastname: Velasco-Loyden
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (E.C., M.G.L.-R., M.D.-L., G.V.-L., J.R.R.-A., V.C.S.); and Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (C.J.-N., M.T.G.-P.).
authors.forename: Jesús Rafael
authors.initials: JR
authors.lastname: Rodríguez-Aguilera
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (E.C., M.G.L.-R., M.D.-L., G.V.-L., J.R.R.-A., V.C.S.); and Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (C.J.-N., M.T.G.-P.).
authors.forename: Concepción
authors.initials: C
authors.lastname: José-Nuñez
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (E.C., M.G.L.-R., M.D.-L., G.V.-L., J.R.R.-A., V.C.S.); and Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (C.J.-N., M.T.G.-P.).
authors.forename: Marietta
authors.initials: M
authors.lastname: Tuena de Gómez-Puyou
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (E.C., M.G.L.-R., M.D.-L., G.V.-L., J.R.R.-A., V.C.S.); and Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (C.J.-N., M.T.G.-P.) vchagoya@ifc.unam.mx.
authors.forename: Victoria
authors.initials: V
authors.lastname: Chagoya de Sánchez
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D042967:Electron Transport Complex I / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D016588:Anticarcinogenic Agents; C548964:adenosine 2-aminosuccinic acid-2-(6-amino-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol; D000255:Adenosine Triphosphate; D042967:Electron Transport Complex I; D000241:Adenosine