Attenuation of liver cancer development by oral glycerol supplementation in the rat
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.
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).
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.
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.
KeywordsProliferation Apoptosis Glycerol Liver preneoplasia Oxidative stress
This work was supported by research grants PICT 2013 No. 1693 (Alvarez) from Agencia Nacional de Promoción Científica y Tecnológica and by PIP No. 0062 (Carrillo and Alvarez) from Consejo Nacional de Investigaciones Científicas y Técnicas. The authors thank Wiener Lab for the generous gift of critical reagents for glycerol phosphate enzymatic determination and Dr. Mauricio Rassetto for his expert technical assistance in performing this procedure.
Compliance with ethical standards
Animal studies were performed according to the NIH “Guide for the Care and Use of Laboratory Animals” (Publication no. 25–28, revised 1996) and approved by the local animal care and use committee (Permission 6060/234, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR).
Conflict of interest
The authors declare that they have no conflict of interest.
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