Supplementing Soy-Based Diet with Creatine in Rats: Implications for Cardiac Cell Signaling and Response to Doxorubicin.

Kay, Laurence; Potenza, Lucia; Hininger-Favier, Isabelle; Roth, Hubert; Attia, Stéphane; Tellier, Cindy; Zuppinger, Christian; Calcabrini, Cinzia; Sestili, Piero; Wallimann, Theo; Schlattner, Uwe; Tokarska-Schlattner, Malgorzata (2022). Supplementing Soy-Based Diet with Creatine in Rats: Implications for Cardiac Cell Signaling and Response to Doxorubicin. Nutrients, 14(3) Molecular Diversity Preservation International MDPI 10.3390/nu14030583

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Nutritional habits can have a significant impact on cardiovascular health and disease. This may also apply to cardiotoxicity caused as a frequent side effect of chemotherapeutic drugs, such as doxorubicin (DXR). The aim of this work was to analyze if diet, in particular creatine (Cr) supplementation, can modulate cardiac biochemical (energy status, oxidative damage and antioxidant capacity, DNA integrity, cell signaling) and functional parameters at baseline and upon DXR treatment. Here, male Wistar rats were fed for 4 weeks with either standard rodent diet (NORMAL), soy-based diet (SOY), or Cr-supplemented soy-based diet (SOY + Cr). Hearts were either freeze-clamped in situ or following ex vivo Langendorff perfusion without or with 25 μM DXR and after recording cardiac function. The diets had distinct cardiac effects. Soy-based diet (SOY vs. NORMAL) did not alter cardiac performance but increased phosphorylation of acetyl-CoA carboxylase (ACC), indicating activation of rather pro-catabolic AMP-activated protein kinase (AMPK) signaling, consistent with increased ADP/ATP ratios and lower lipid peroxidation. Creatine addition to the soy-based diet (SOY + Cr vs. SOY) slightly increased left ventricular developed pressure (LVDP) and contractility dp/dt, as measured at baseline in perfused heart, and resulted in activation of the rather pro-anabolic protein kinases Akt and ERK. Challenging perfused heart with DXR, as analyzed across all nutritional regimens, deteriorated most cardiac functional parameters and also altered activation of the AMPK, ERK, and Akt signaling pathways. Despite partial reprogramming of cell signaling and metabolism in the rat heart, diet did not modify the functional response to supraclinical DXR concentrations in the used acute cardiotoxicity model. However, the long-term effect of these diets on cardiac sensitivity to chronic and clinically relevant DXR doses remains to be established.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

UniBE Contributor:

Zuppinger, Christian

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2072-6643

Publisher:

Molecular Diversity Preservation International MDPI

Language:

English

Submitter:

Pubmed Import

Date Deposited:

15 Mar 2022 10:58

Last Modified:

05 Dec 2022 16:15

Publisher DOI:

10.3390/nu14030583

PubMed ID:

35276943

Uncontrolled Keywords:

adenosine 5′-monopnophosphate-activated protein kinase anthracyclines cardiac signaling cardiotoxicity creatine supplementation doxorubicin soy vegetarian/vegan diet

BORIS DOI:

10.48350/167393

URI:

https://boris.unibe.ch/id/eprint/167393

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