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Chavez, Enrique; Guadalupe Lozano-Rosas, Maria; Dominguez-Lopez, Mariana; Velasco-Loyden, Gabriela; Rafael Rodriguez-Aguilera, Jesus; Jose-Nunez, Concepcion; Tuena de Gomez-Puyou, Marietta; Chagoya de Sanchez, Victoria (2017)

FUNCTIONAL, METABOLIC, AND DYNAMIC MITOCHONDRIAL CHANGES IN THE RAT CIRRHOSIS-HEPATOCELLULAR CARCINOMA MODEL AND THE PROTECTIVE EFFECT OF IFC-305

J. Pharmacol. Exp. Ther. 361(2):292-302
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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.