Alejo M Capiglioni1, Florencia Lorenzetti1, Ariel D Quiroga1,2, Juan P Parody1, María T Ronco1, Gerardo B Pisani2, María C Carrillo1,2, María P Ceballos1, María de Luján Alvarez3,4. 1. Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Suipacha 570, S2002LRL, Rosario, Argentina. 2. Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Suipacha 570, S2002LRL, Rosario, Argentina. 3. Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Suipacha 570, S2002LRL, Rosario, Argentina. alvarez@ifise-conicet.gov.ar. 4. Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Suipacha 570, S2002LRL, Rosario, Argentina. alvarez@ifise-conicet.gov.ar.
Abstract
PURPOSE: Glycerol usage is increasing in food industry for human and animal nutrition. This study analyzed the impact of glycerol metabolism when orally supplemented during the early stage of rat liver carcinogenesis. METHODS: Wistar rats were subjected to a 2-phase model of hepatocarcinogenesis (initiated-promoted, IP group). IP animals also received glycerol by gavage (200 mg/kg body weight, IPGly group). RESULTS: Glycerol treatment reduced the volume of preneoplastic lesions by decreasing the proliferative status of liver foci, increasing the expression of p53 and p21 proteins and reducing the expression of cyclin D1 and cyclin-dependent kinase 1. Besides, apoptosis was enhanced in IPGly animals, given by an increment of Bax/Bcl-2 ratio, Bad and PUMA mitochondrial expression, a concomitant increase in cytochrome c release and caspase-3 activation. Furthermore, hepatic levels of glycerol phosphate and markers of oxidative stress were increased in IPGly rats. Oxidative stress intermediates act as intracellular messengers, inducing p53 activation and changes in JNK and Erk signaling pathways, with JNK activation and Erk inhibition. CONCLUSION: The present work provides novel data concerning the preventive actions of glycerol during the development of liver cancer and represents an economically feasible intervention to treat high-risk individuals.
PURPOSE:Glycerol usage is increasing in food industry for human and animal nutrition. This study analyzed the impact of glycerol metabolism when orally supplemented during the early stage of ratliver carcinogenesis. METHODS:Wistar rats were subjected to a 2-phase model of hepatocarcinogenesis (initiated-promoted, IP group). IP animals also received glycerol by gavage (200 mg/kg body weight, IPGly group). RESULTS:Glycerol treatment reduced the volume of preneoplastic lesions by decreasing the proliferative status of liver foci, increasing the expression of p53 and p21 proteins and reducing the expression of cyclin D1 and cyclin-dependent kinase 1. Besides, apoptosis was enhanced in IPGly animals, given by an increment of Bax/Bcl-2 ratio, Bad and PUMA mitochondrial expression, a concomitant increase in cytochrome c release and caspase-3 activation. Furthermore, hepatic levels of glycerol phosphate and markers of oxidative stress were increased in IPGlyrats. Oxidative stress intermediates act as intracellular messengers, inducing p53 activation and changes in JNK and Erk signaling pathways, with JNK activation and Erk inhibition. CONCLUSION: The present work provides novel data concerning the preventive actions of glycerol during the development of liver cancer and represents an economically feasible intervention to treat high-risk individuals.
Authors: María Laura Casella; Juan Pablo Parody; María Paula Ceballos; Ariel Darío Quiroga; María Teresa Ronco; Daniel Eleazar Francés; Juan Alberto Monti; Gerardo Bruno Pisani; Cristina Ester Carnovale; María Cristina Carrillo; María de Luján Alvarez Journal: Mol Nutr Food Res Date: 2013-10-01 Impact factor: 5.914
Authors: Ariel D Quiroga; María de Luján Alvarez; Juan P Parody; María Teresa Ronco; Daniel E Francés; Gerardo B Pisani; Cristina E Carnovale; María Cristina Carrillo Journal: Biochem Pharmacol Date: 2007-02-16 Impact factor: 5.858