Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration

Lourdes Sánchez-Sevilla,Rolando Hernández-Muñoz,Edgar Mendieta-Condado

doi:10.1186/s12967-016-1062-y

Lourdes Sánchez-Sevilla, Rolando Hernández-Muñoz + Show 1 more

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https://doi.org/10.1186/s12967-016-1062-y

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Abstract

BackgroundThe pre-treatment with α-tocopherol inhibits progression of rat liver proliferation induced by partial hepatectomy (PH), by decreasing and/or desynchronizing cyclin D1 expression and activation into the nucleus, activation and nuclear translocation of STAT-1 and -3 proteins and altering retinoid metabolism. Interactions between retinoic acid and polyamines have been reported in the PH-induced rat liver regeneration. Therefore, we evaluated the effect of low dosage of α-tocopherol on PH-induced changes in polyamine metabolism.MethodsThis study evaluated the participation of polyamine synthesis and metabolism during α-tocopherol-induced inhibition of rat liver regeneration. In PH-rats (Wistar) treated with α-tocopherol and putrescine, parameters indicative of cell proliferation, lipid peroxidation, ornithine decarboxylase expression (ODC), and polyamine levels, were determined.ResultsPre-treatment with α-tocopherol to PH-animals exerted an antioxidant effect, shifting earlier the increased ODC activity and expression, temporally affecting polyamine synthesis and ornithine metabolism. Whereas administration of putrescine induced minor changes in PH-rats, the concomitant treatment actually counteracted most of adverse actions exerted by α-tocopherol on the remnant liver, restituting its proliferative potential, without changing its antioxidant effect. Putrescine administration to these rats was also associated with lower ODC expression and activity in the proliferating liver, but the temporally shifting in the amount of liver polyamines induced by α-tocopherol, was also “synchronized” by the putrescine administration. The latter is supported by the fact that a close relationship was observed between fluctuations of polyamines and retinoids.ConclusionsPutrescine counteracted most adverse actions exerted by α-tocopherol on rat liver regeneration, restoring liver proliferative potential and restituting the decreased retinoid levels induced by α-tocopherol. Therefore interactions between polyamines and retinol, mediated by the oxidant status, should be taken into consideration in the development of new therapeutic strategies for pathologies occurring with liver cell proliferation.

Highlights

The pre-treatment with α-tocopherol inhibits progression of rat liver proliferation induced by partial hepatectomy (PH), by decreasing and/or desynchronizing cyclin D1 expression and activation into the nucleus, activation and nuclear translocation of signal transducer and activator of transcription (STAT)-1 and -3 proteins and altering retinoid metabolism
We have demonstrated that the oxidant status can control the progression of partial hepatectomy (PH)induced rat liver regeneration [8, 9], and treatment with the α-tocopherol promotes an early termination of priming cell events, culminating in a partial inhibition of rat liver regeneration [10]
Liver histology and parameters indicative of liver cell proliferation in animals subjected to PH and treated with α‐tocopherol and/or putrescine The cytosolic activity of thymidine kinase (TK) is considered as a reliable parameter for evaluating DNA synthesis [27]

Summary

Introduction

The pre-treatment with α-tocopherol inhibits progression of rat liver proliferation induced by partial hepatectomy (PH), by decreasing and/or desynchronizing cyclin D1 expression and activation into the nucleus, activation and nuclear translocation of STAT-1 and -3 proteins and altering retinoid metabolism. Abdominal obesity is a risk factor associated with enhanced oxidative stress; it has proved that this condition has relationships with dietary vitamin E and A intake and genetic variants of thioredoxin and catechol-O-methyltransferase [7] In this regard, we have demonstrated that the oxidant status can control the progression of partial hepatectomy (PH)induced rat liver regeneration [8, 9], and treatment with the α-tocopherol promotes an early termination of priming cell events, culminating in a partial inhibition of rat liver regeneration [10]. We have demonstrated that interactions between α-tocopherol and retinoid compounds (retinol, retinal, and retinoic acid) are important for impacting rat liver regeneration after PH In this context, an anti-tumor effect of VE might be attributed to a kind of disruption of signal transduction [14], as we have already explored [10, 15]. It has been highlighted the role of STAT3 signaling in liver injury, steatosis, inflammation, regeneration, fibrosis, and hepato-carcinogenesis, proposing that cytokines and small molecules that activate STAT3 in hepatocytes may readily have therapeutic benefits to treat liver diseases, including cancer [16]

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