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Bioaccumulation of resveratrol metabolites in myocardial tissue is dose-time dependent and related to cardiac hemodynamics in diabetic rats

Journal Article


Abstract


  • Background and aims: Trans-resveratrol (RSV) is a natural compound occurring in different foods and plants, which in vivo is rapidly conjugated with glucuronic acid and sulfate. Despite its demonstrated cardioprotective activity, the bioaccumulation of RSV or its metabolites in cardiac tissue is still unknown. Methods and results: Diabetic rats were randomized to 1, 3 or 6 weeks of RSV treatment at two different doses (1 or 5mg/kg/day). A dose and time-dependent accumulation was observed, with no detectable levels of RSV metabolites found in heart tissues after 1 week and significant concentrations of RSV-3-sulfate and RSV-3-glucuronide after 6 weeks of treatment (0.05nmol/g of tissue and 0.01nmol/g of tissue, respectively). Tissue accumulation of RSV metabolites was accompanied by an improvement of cardiac function in long-term diabetes, when myocardial morpho-functional damage is more evident, with an almost complete recovery of all hemodynamic parameters, at the highest RSV dose. Conclusion: Even if a higher concentration of RSV in tissues cannot be ruled out after constant oral administration, an accumulation coherent with what is usually evaluated in cell based mechanistic studies is largely unattainable and the RSV unconjugated form would not be present in this paradigm. The current investigation provides data on myocardial tissue concentrations of RSV metabolites, after short/medium term RSV treatment. This knowledge constitutes a basic requirement for future studies aimed at reliably defining the molecular pathways underlying RSV-mediated cardioprotective effects and opens up new perspectives for research focused on testing phenolic compounds as adjuvants in degenerative heart diseases. © 2013 Elsevier B.V.

Publication Date


  • 2014

Citation


  • Bresciani, L., Calani, L., Bocchi, L., Delucchi, F., Savi, M., Ray, S., . . . Del Rio, D. (2014). Bioaccumulation of resveratrol metabolites in myocardial tissue is dose-time dependent and related to cardiac hemodynamics in diabetic rats. Nutrition, Metabolism and Cardiovascular Diseases, 24(4), 408-415. doi:10.1016/j.numecd.2013.09.008

Scopus Eid


  • 2-s2.0-84897078117

Web Of Science Accession Number


Start Page


  • 408

End Page


  • 415

Volume


  • 24

Issue


  • 4

Abstract


  • Background and aims: Trans-resveratrol (RSV) is a natural compound occurring in different foods and plants, which in vivo is rapidly conjugated with glucuronic acid and sulfate. Despite its demonstrated cardioprotective activity, the bioaccumulation of RSV or its metabolites in cardiac tissue is still unknown. Methods and results: Diabetic rats were randomized to 1, 3 or 6 weeks of RSV treatment at two different doses (1 or 5mg/kg/day). A dose and time-dependent accumulation was observed, with no detectable levels of RSV metabolites found in heart tissues after 1 week and significant concentrations of RSV-3-sulfate and RSV-3-glucuronide after 6 weeks of treatment (0.05nmol/g of tissue and 0.01nmol/g of tissue, respectively). Tissue accumulation of RSV metabolites was accompanied by an improvement of cardiac function in long-term diabetes, when myocardial morpho-functional damage is more evident, with an almost complete recovery of all hemodynamic parameters, at the highest RSV dose. Conclusion: Even if a higher concentration of RSV in tissues cannot be ruled out after constant oral administration, an accumulation coherent with what is usually evaluated in cell based mechanistic studies is largely unattainable and the RSV unconjugated form would not be present in this paradigm. The current investigation provides data on myocardial tissue concentrations of RSV metabolites, after short/medium term RSV treatment. This knowledge constitutes a basic requirement for future studies aimed at reliably defining the molecular pathways underlying RSV-mediated cardioprotective effects and opens up new perspectives for research focused on testing phenolic compounds as adjuvants in degenerative heart diseases. © 2013 Elsevier B.V.

Publication Date


  • 2014

Citation


  • Bresciani, L., Calani, L., Bocchi, L., Delucchi, F., Savi, M., Ray, S., . . . Del Rio, D. (2014). Bioaccumulation of resveratrol metabolites in myocardial tissue is dose-time dependent and related to cardiac hemodynamics in diabetic rats. Nutrition, Metabolism and Cardiovascular Diseases, 24(4), 408-415. doi:10.1016/j.numecd.2013.09.008

Scopus Eid


  • 2-s2.0-84897078117

Web Of Science Accession Number


Start Page


  • 408

End Page


  • 415

Volume


  • 24

Issue


  • 4