Calorie restriction potentiates epigallocatechin-3-gallate-mediated Nrf2 activation in hepatocytes of aged rats

Abstract

Objective: To explore the combinatorial effect of epigallocatechin-3-gallate (EGCG) and calorie restriction on activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor involved in the antioxidant defense system of aged rats. Methods: Aged male Wistar rats were calorie-restricted and treated with EGCG orally for 45 days. The initial body weight of aged rats was recorded, and the final body weight was measured at the end of the experimental period. Serum lipid and lipoprotein status, oxidative stress markers such as free radicals and malondialdehyde levels, and reduced glutathione were assessed. In addition, RT-PCR and Western blotting analyses were performed. Results: Calorie restriction potentiated the effect of EGCG on enhancing antioxidant status, improving the levels of serum lipid and lipoproteins, upregulating Nrf2 and Bcl2, and downregulating Keap1, cullin3, Bax and cytochrome c in aged rats. Conclusions: Calorie restriction can promote EGCG-mediated Nrf2 activation in aged rats. This preliminary finding paves the way for a combinatory approach to replenishing the antioxidant status during aging, thereby reducing the risk for age-associated degenerative diseases.

Keywords

Aging / Reactive oxygen species / Calorie restriction / EGCG / Nrf2 / Antioxidant

Acknowledgments

The authors wish to acknowledge the financial support offered by UGC SAP Programme, University of Madras, Chennai, India for conducting this study.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

The article was financially supported by UGC SAP Programme, University of Madras, Chennai, India.

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

Material preparation, data collection and analysis were performed by MM, RR and KP. Study design and conception were done by MM, RR, RJ and KP. The first draft of the manuscript was written by MM and RR. Previous version and revised version of the manuscript were commented by RR, RJ, TM and KP. Final manuscript was read and approved by MM, RR, RJ, TM and KP.

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