Essential Amino Acids-Rich Diet Increases Cardiomyocytes Protection in Doxorubicin-Treated Mice

Author:

Corsetti Giovanni1ORCID,Romano Claudia1,Pasini Evasio2,Scarabelli Tiziano3,Chen-Scarabelli Carol4,Dioguardi Francesco S.5ORCID

Affiliation:

1. Division of Human Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy

2. Italian Association of Functional Medicine, 20855 Lesmo (Milan), Italy

3. Center for Heart and Vessel Preclinical Studies, St. John Hospital and Medical Center, Wayne State University, Detroit, MI 48236, USA

4. Division of Cardiology, Richmond Veterans Affairs Medical Center (VAMC), Richmond, VA 23249, USA

5. Department of Internal Medicine, University of Cagliari, 09042 Monserrato (Cagliari), Italy

Abstract

Background: Doxorubicin (Doxo) is a widely prescribed drug against many malignant cancers. Unfortunately, its utility is limited by its toxicity, in particular a progressive induction of congestive heart failure. Doxo acts primarily as a mitochondrial toxin, with consequent increased production of reactive oxygen species (ROS) and attendant oxidative stress, which drives cardiac dysfunction and cell death. A diet containing a special mixture of all essential amino acids (EAAs) has been shown to increase mitochondriogenesis, and reduce oxidative stress both in skeletal muscle and heart. So, we hypothesized that such a diet could play a favorable role in preventing Doxo-induced cardiomyocyte damage. Methods: Using transmission electron microscopy, we evaluated cells’ morphology and mitochondria parameters in adult mice. In addition, by immunohistochemistry, we evaluated the expression of pro-survival marker Klotho, as well as markers of necroptosis (RIP1/3), inflammation (TNFα, IL1, NFkB), and defense against oxidative stress (SOD1, glutathione peroxidase, citrate synthase). Results: Diets with excess essential amino acids (EAAs) increased the expression of Klotho and enhanced anti-oxidative and anti-inflammatory responses, thereby promoting cell survival. Conclusion: Our results further extend the current knowledge about the cardioprotective role of EAAs and provide a novel theoretical basis for their preemptive administration to cancer patients undergoing chemotherapy to alleviate the development and severity of Doxo-induced cardiomyopathy.

Funder

Dolomite-Franchi S.p.a.

Publisher

MDPI AG

Subject

Food Science,Nutrition and Dietetics

Reference72 articles.

1. Anthracyclines in the treatment of cancer: An overview;Hortobagyi;Drugs,1997

2. Anthracyclines in the treatment of gynecologic malignancies;Maluf;Gynecol. Oncol.,2002

3. Early anthracycline cardiotoxicity;Bristow;Am. J. Med.,1978

4. A clinicopathologic analysis of adriamycin cardiotoxicity;Lefrak;Cancer,1973

5. Anthracycline-induced clinical heart failure in a cohort of 607 children: Long-term follow-up study;Kremer;J. Clin. Oncol.,2001

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