Essential Amino Acids-Rich Diet Increases Cardiomyocytes Protection in Doxorubicin-Treated Mice
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals and Treatments
2.2. Transmission Electron Microscopy (TEM)
2.3. Morphometry
2.4. Histochemistry
2.5. Immunohistochemistry
2.6. Statistics
3. Results
3.1. Morphology
3.2. Histochemistry
3.3. Electron Microscopy
3.4. Immunohistochemistry
4. Discussion
4.1. Clinical Implications
4.2. Limits of the Study
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Hortobagyi, G.N. Anthracyclines in the treatment of cancer: An overview. Drugs 1997, 54, 1–7. [Google Scholar]
- Maluf, F.C.; Spriggs, D. Anthracyclines in the treatment of gynecologic malignancies. Gynecol. Oncol. 2002, 85, 18–31. [Google Scholar] [CrossRef]
- Bristow, M.R.; Thompson, P.D.; Martin, R.P.; Mason, J.W.; Billingham, M.E.; Harrison, D.C. Early anthracycline cardiotoxicity. Am. J. Med. 1978, 65, 823–832. [Google Scholar] [CrossRef]
- Lefrak, E.A.; Pitha, J.; Rosenheim, S.; Gottlieb, J.A. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer 1973, 32, 302–314. [Google Scholar] [CrossRef]
- Kremer, L.; van Dalen, E.; Offringa, M.; Ottenkamp, J.; Voûte, P. Anthracycline-induced clinical heart failure in a cohort of 607 children: Long-term follow-up study. J. Clin. Oncol. 2001, 19, 191–196. [Google Scholar] [CrossRef]
- Swain, S.M.; Whaley, F.S.; Ewer, M.S. Congestive heart failure in patients treated with doxorubicin: A retrospective analysis of three trials. Cancer 2003, 97, 2869–2879. [Google Scholar] [CrossRef]
- Gewirtz, D.A. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem. Pharmacol. 1999, 57, 727–741. [Google Scholar] [CrossRef]
- Minotti, G.; Menna, P.; Salvatorelli, E.; Cairo, G.; Gianni, L. Anthracyclines: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. 2004, 56, 185–229. [Google Scholar] [CrossRef][Green Version]
- Xu, F.; Li, X.; Liu, L.; Xiao, X.; Zhang, L.; Zhang, S.; Lin, P.; Wang, X.; Wang, Y.; Li, Q. Attenuation of doxorubicin-induced cardiotoxicity by esculetin through modulation of Bmi-1 expression. Exp. Ther. Med. 2017, 14, 2216–2220. [Google Scholar] [CrossRef][Green Version]
- Khan, A.A.; Ashraf, A.; Singh, R.; Rahim, A.; Rostom, W.; Hussain, M.; Renner, I.; Collins, N.J. Incidence, time of occurrence and response to heart failure therapy in patients with anthracycline cardiotoxicity. Intern. Med. J. 2017, 47, 104–109. [Google Scholar] [CrossRef]
- Takemura, G.; Fujiwara, H. Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management. Prog. Cardiovasc. Dis. 2007, 49, 330–352. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.W.; Shi, J.; Li, Y.J.; Wei, L. Cardiomyocyte death in doxorubicin-induced cardiotoxicity. Arch. Immunol. Ther. Exp. 2009, 57, 435–445. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Lagoa, R.; Gañán, C.; López-Sánchez, C.; García-Martínez, V.; Gutierrez-Merino, C. The decrease of NAD(P)H: Quinone oxidoreductase 1 activity and increase of ROS production by NADPH oxidases are early biomarkers in doxorubicin cardiotoxicity. Biomarkers 2014, 19, 142–153. [Google Scholar] [CrossRef][Green Version]
- Flati, V.; Corsetti, G.; Pasini, E.; Rufo, A.; Romano, C.; Dioguardi, F.S. Nutrient, nitrogen requirements, exercise and chemotherapy-induced toxicity in cancer patients. A puzzle of contrasting truths? Anticancer Agents Med. Chem. 2016, 16, 89–100. [Google Scholar] [CrossRef]
- Tsutsui, H.; Kinugawa, S.; Matsushima, S. Oxidative stress and heart failure. Am. J. Physiol. Heart. Circ. Physiol. 2011, 301, H2181–H2190. [Google Scholar] [CrossRef][Green Version]
- Yamamoto, M.; Clark, J.D.; Pastor, J.V.; Gurnani, P.; Nandi, A.; Kurosu, H.; Miyoshi, M.; Ogawa, Y.; Castrillon, D.H.; Rosenblatt, K.P.; et al. Regulation of oxidative stress by the anti-aging hormone klotho. J. Biol. Chem. 2005, 280, 38029–38034. [Google Scholar] [CrossRef][Green Version]
- Kuro-O, M. Klotho. Pflug. Arch. 2010, 459, 333–343. [Google Scholar] [CrossRef]
- Semba, R.D.; Cappola, A.R.; Sun, K.; Bandinelli, S.; Dalal, M.; Crasto, C.; Guralnik, J.M.; Ferrucci, L. Plasma klotho and cardiovascular disease in adults. J. Am. Geriatr. Soc. 2011, 59, 1596–1601. [Google Scholar] [CrossRef][Green Version]
- Corsetti, G.; Pasini, E.; Scarabelli, T.M.; Romano, C.; Agrawal, P.R.; Chen-Scarabelli, C.; Knight, R.; Saravolatz, L.; Narula, J.; Ferrari-Vivaldi, M.; et al. Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease. Geriatr. Cardiol. 2016, 13, 701–711. [Google Scholar] [CrossRef]
- Kostin, S.; Pool, L.; Elsässer, A.; Hein, S.; Drexler, H.C.; Arnon, E.; Hayakawa, Y.; Zimmermann, R.; Bauer, E.; Klövekorn, W.P.; et al. Myocytes die by multiple mechanisms in failing human hearts. Circ. Res. 2003, 92, 715–724. [Google Scholar] [CrossRef][Green Version]
- Corsetti, G.; Chen-Scarabelli, C.; Romano, C.; Pasini, E.; Dioguardi, F.S.; Onorati, F.; Knight, R.; Patel, H.; Saravolatz, L.; Faggian, G.; et al. Autophagy and oncosis/necroptosis are enhanced in cardiomyocytes from heart failure patients. Med. Sci. Monit. Basic Res. 2019, 25, 33–44. [Google Scholar] [CrossRef] [PubMed]
- Lemasters, J.J.V. Necrapoptosis and the mitochondrial permeability transition: Shared pathways to necrosis and apoptosis. Am. J. Physiol. Gastrointest. Liver Physiol. 1999, 276, G1–G6. [Google Scholar] [CrossRef]
- Chandrashekhar, Y.; Narula, J. Death hath a thousand doors to let out life. Circ. Res. 2003, 92, 710–714. [Google Scholar] [CrossRef] [PubMed]
- Takemura, G.; Miyata, S.; Kawase, Y.; Okada, H.; Maruyama, R.; Fujiwara, H. Autophagic degeneration and death of cardiomyocytes in heart failure. Autophagy 2006, 2, 212–214. [Google Scholar] [CrossRef][Green Version]
- Kanduc, D.; Mittelman, A.; Serpico, R.; Sinigaglia, E.; Sinha, A.A.; Natale, C.; Santacroce, R.; Di Corcia, M.G.; Lucchese, A.; Dini, L.; et al. Cell death: Apoptosis versus necrosis (review). Int. J. Oncol. 2002, 21, 165–170. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Meylan, E.; Tschopp, J. The RIP kinases: Crucial integrators of cellular stress. Trends Biochem. Sci. 2005, 30, 151–159. [Google Scholar] [CrossRef] [PubMed]
- Adameova, A.; Goncalvesova, E.; Szobi, A.; Dhalla, N.S. Necroptotic cell death in failing heart: Relevance and proposed mechanisms. Heart Fail. Rev. 2016, 21, 213–221. [Google Scholar] [CrossRef] [PubMed]
- Stanger, B.Z.; Leder, P.; Lee, T.H.; Kim, E.; Seed, B. RIP: A novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell 1995, 81, 513–523. [Google Scholar] [CrossRef][Green Version]
- Festjens, N.; Vanden Berghe, T.; Cornelis, S.; Vandenabeele, P. RIP1, a kinase on the crossroads of a cell’s decision to live or die. Cell Death Differ. 2007, 14, 400–410. [Google Scholar] [CrossRef]
- Lee, T.H.; Shank, J.; Cusson, N.; Kelliher, M.A. The kinase activity of Rip1 is not required for tumor necrosis factor-alpha-induced IkappaB kinase or p38 MAP kinase activation or for the ubiquitination of Rip1 by Traf2. J. Biol. Chem. 2004, 279, 33185–33191. [Google Scholar] [CrossRef][Green Version]
- Cho, Y.S.; Challa, S.; Moquin, D.; Genga, R.; Ray, T.D.; Guildford, M.; Chan, F.K. Phosphorylation driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 2009, 137, 1112–1123. [Google Scholar] [CrossRef] [PubMed][Green Version]
- He, S.; Wang, L.; Miao, L.; Wang, T.; Du, F.; Zhao, L.; Wang, X. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 2009, 137, 1100–1111. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Zhang, D.W.; Shao, J.; Lin, J.; Zhang, N.; Lu, B.J.; Lin, S.C.; Dong, M.Q.; Han, J. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 2009, 325, 332–336. [Google Scholar] [CrossRef] [PubMed]
- Moriwaki, K.; Ka-Ming Chan, F. RIP3: A molecular switch for necrosis and inflammation. Genes Dev. 2013, 27, 1640–1649. [Google Scholar] [CrossRef][Green Version]
- Qian, Y.; Guo, X.; Che, L.; Guan, X.; Wu, B.; Lu, R.; Zhu, M.; Pang, H.; Yan, Y.; Ni, Z.; et al. Klotho reduces necroptosis by targeting oxidative stress involved in renal ischemic-reperfusion injury. Cell. Physiol. Biochem. 2018, 45, 2268–2282, Erratum in Cell Physiol. Biochem. 2021, 55, 508–509. [Google Scholar] [CrossRef][Green Version]
- Romano, C.; Corsetti, G.; Flati, V.; Pasini, E.; Picca, A.; Calvani, R.; Marzetti, E.; Saverio Dioguardi, F. Influence of diets with varying essential/nonessential amino acid ratios on mouse lifespan. Nutrients 2019, 11, 1367. [Google Scholar] [CrossRef][Green Version]
- Pansarasa, O.; Flati, V.; Corsetti, G.; Brocca, L.; Pasini, E.; D’Antona, G. Oral amino acid supplementation counteracts age-induced sarcopenia in elderly rats. Am. J. Cardiol. 2008, 101, 35E–41E. [Google Scholar] [CrossRef]
- Tedesco, L.; Corsetti, G.; Ruocco, C.; Ragni, M.; Rossi, F.; Carruba, M.O.; Valerio, A.; Nisoli, E. A specific amino acid formula prevents alcoholic liver disease in rodents. Am. J. Physiol. Gastrointest. Liver Physiol. 2018, 314, G566–G582. [Google Scholar] [CrossRef]
- D’Antona, G.; Tedesco, L.; Ruocco, C.; Corsetti, G.; Ragni, M.; Fossati, A.; Saba, E.; Fenaroli, F.; Montinaro, M.; Carruba, M.O.; et al. A peculiar formula of essential amino acids prevents rosuvastatin myopathy in mice. Antioxid. Redox Signal. 2016, 25, 595–608. [Google Scholar] [CrossRef][Green Version]
- Corsetti, G.; Stacchiotti, A.; Tedesco, L.; D’Antona, G.; Pasini, E.; Dioguardi, F.S.; Nisoli, E.; Rezzani, R. Essential amino acid supplementation decreases liver damage induced by chronic ethanol consumption in rats. Int. J. Immunopathol. Pharmacol. 2011, 24, 611–619. [Google Scholar] [CrossRef]
- Corsetti, G.; D’Antona, G.; Ruocco, C.; Stacchiotti, A.; Romano, C.; Tedesco, L.; Dioguardi, F.; Rezzani, R.; Nisoli, E. Dietary supplementation with essential amino acids boosts the beneficial effects of rosuvastatin on mouse kidney. Amino Acids 2014, 46, 2189–2203. [Google Scholar] [CrossRef] [PubMed][Green Version]
- D’Antona, G.; Ragni, M.; Cardile, A.; Tedesco, L.; Dossena, M.; Bruttini, F.; Caliaro, F.; Corsetti, G.; Bottinelli, R.; Carruba, M.O.; et al. Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice. Cell Metab. 2010, 12, 362–372. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Suliman, H.B.; Carraway, M.S.; Ali, A.S.; Reynolds, C.M.; Welty-Wolf, K.E.; Piantadosi, C.A. The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy. J. Clin. Investig. 2007, 117, 3730–3741. [Google Scholar] [CrossRef][Green Version]
- Corsetti, G.; Pasini, E.; D’Antona, G.; Nisoli, E.; Flati, V.; Assanelli, D.; Dioguardi, F.S.; Bianchi, R. Morphometric changes induced by amino acid supplementation in skeletal and cardiac muscles of old mice. Am. J. Cardiol. 2008, 101, 26E–34E. [Google Scholar] [CrossRef] [PubMed]
- Dayan, D.; Hiss, Y.; Hirshberg, A.; Bubis, J.J.; Wolman, M. Are the polarization colors of picrosirius red-stained collagen determined only by the diameter of the fibers? Histochemistry 1989, 93, 27–29. [Google Scholar] [CrossRef]
- Williams, I.F.; McCullagh, K.G.; Silver, I.A. The distribution of types I and III collagen and fibronectin in the healing equine tendon. Connect. Tissue Res. 1984, 12, 211–227. [Google Scholar] [CrossRef]
- Vranes, D.; Cooper, M.E.; Dilley, R.J. Cellular mechanisms of diabetic vascular hypertrophy. Microvasc Res. 1999, 57, 8–18. [Google Scholar] [CrossRef]
- Koren, R.; Yaniv, E.; Kristt, D.; Shvero, J.; Veltman, V.; Grushko, I.; Feinmesser, R.; Sulkes, J.; Gal, R. Capsular collagen staining of follicular thyroid neoplasm by picrosirius red: Role in differential diagnosis. Acta Histochem. 2001, 103, 151–157. [Google Scholar] [CrossRef]
- Corsetti, G.; Flati, V.; Sanità, P.; Pasini, E.; Dioguardi, F.S. Protect and counter-attack: Nutritional supplementation with essential amino acid ratios reduces doxorubicin–induced cardiotoxicity In Vivo and promote cancer cell death In Vitro. J. Cytol. Histol. 2015, 6, 5. [Google Scholar] [CrossRef][Green Version]
- Corsetti, G.; Pasini, E.; Romano, C.; Chen-Scarabelli, C.; Scarabelli, T.M.; Flati, V.; Saravolatz, L.; Dioguardi, F.S. How can malnutrition affect autophagy in chronic heart failure? focus and perspectives. Int. J. Mol. Sci. 2021, 22, 3332. [Google Scholar] [CrossRef]
- Corsetti, G.; Romano, C.; Codenotti, S.; Pasini, E.; Fanzani, A.; Dioguardi, F.S. Essential amino acids-rich diet decreased adipose tissue storage in adult mice: A preliminary histopathological study. Nutrients 2022, 14, 2915. [Google Scholar] [CrossRef] [PubMed]
- Guo, Y.; Zhuang, X.; Huang, Z.; Zou, J.; Yang, D.; Hu, X.; Du, Z.; Wang, L.; Liao, X. Klotho protects the heart from hyperglycemia-induced injury by inactivating ROS and NF-κB-mediated inflammation both In Vitro and In Vivo. Biochim. Biophys. Acta Mol. Basis Dis. 2018, 1864, 238–251. [Google Scholar] [CrossRef] [PubMed]
- Zhu, H.; Gao, Y.; Zhu, S.; Cui, Q.; Du, J. Klotho improves cardiac function by suppressing reactive oxygen species (ROS) mediated apoptosis by modulating Mapks/Nrf2 signaling in doxorubicin-induced cardiotoxicity. Med. Sci. Monit. 2017, 23, 5283–5293. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Weinlich, R.; Oberst, A.; Beere, H.M.; Green, D.R. Necroptosis in development, inflammation and disease. Nat. Rev. Mol. Cell. Biol. 2017, 18, 127–136. [Google Scholar] [CrossRef]
- Liu, Y.; Liu, T.; Lei, T.; Zhang, D.; Du, S.; Girani, L.; Qi, D.; Lin, C.; Tong, R.; Wang, Y. RIP1/RIP3-regulated necroptosis as a target for multifaceted disease therapy (Review). Int. J. Mol. Med. 2019, 44, 771–786. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Newton, K.; Dugger, D.L.; Maltzman, A.; Greve, J.M.; Hedehus, M.; Martin-McNulty, B.; Carano, R.A.; Cao, T.C.; van Bruggen, N.; Bernstein, L.; et al. RIPK3 deficiency or catalytically inactive RIPK1 provides greater benefit than MLKL deficiency in mouse models of inflammation and tissue injury. Cell Death Differ. 2016, 23, 1565–1576. [Google Scholar] [CrossRef][Green Version]
- Hänggi, K.; Vasilikos, L.; Valls, A.F.; Yerbes, R.; Knop, J.; Spilgies, L.M.; Rieck, K.; Misra, T.; Bertin, J.; Gough, P.J.; et al. RIPK1/RIPK3 promotes vascular permeability to allow tumor cell extravasation independent of its necroptotic function. Cell Death Dis. 2017, 8, e2588. [Google Scholar] [CrossRef] [PubMed]
- Luedde, M.; Lutz, M.; Carter, N.; Sosna, J.; Jacoby, C.; Vucur, M.; Gautheron, J.; Roderburg, C.; Borg, N.; Reisinger, F.; et al. RIP3, a kinase promoting necroptotic cell death, mediates adverse remodelling after myocardial infarction. Cardiovasc. Res. 2014, 103, 206–216. [Google Scholar] [CrossRef][Green Version]
- Lin, Y. RIP1-Mediated Signaling Pathways in Cell Survival and Death Control. In Cell Death in Biology and Diseases; Shen, H.M., Vandenabeele, P., Eds.; Humana Press: New York, NY, USA, 2014. [Google Scholar] [CrossRef]
- Wang, H.; Sun, L.; Su, L.; Rizo, J.; Liu, L.; Wang, L.F.; Wang, F.S.; Wang, X. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol. Cell. 2014, 54, 133–146. [Google Scholar] [CrossRef][Green Version]
- O’Donnell, M.A.; Ting, A.T. RIP1 comes back to life as a cell death regulator in TNFR1 signaling. FEBS J. 2011, 278, 877–887. [Google Scholar] [CrossRef][Green Version]
- Zhang, H.; Zhou, X.; Mcquade, T.; Li, J.; Chan, F.K.; Zhang, J. Functional complementation between FADD and RIP1 in embryos and lymphocytes. Nature 2011, 471, 373–376. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Skaug, B.; Jiang, X.; Chen, Z.J. The Role of ubiquitin in NF-kB regulatory pathways. Annu. Rev. Biochem. 2009, 78, 769–796. [Google Scholar] [CrossRef] [PubMed]
- Kaltschmidt, B.; Kaltschmidt, C.; Hofmann, T.G.; Hehner, S.P.; Dröge, W.; Schmitz, M.L. The pro- or anti-apoptotic function of NF-kB is determined by the nature of the apoptotic stimulus. Eur. J. Biochem. 2000, 267, 3828–3835. [Google Scholar] [CrossRef] [PubMed]
- Campbell, K.J.; Rocha, S.; Perkins, N.D. Active repression of antiapoptotic gene expression by RelA(p65) NF-kappa B. Mol. Cell. 2004, 13, 853–865. [Google Scholar] [CrossRef] [PubMed]
- Janssens, S.; Tschopp, J. Signals from within: The DNA-damage-induced NF-κB response. Cell Death Differ. 2006, 13, 773–784. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Zbeki, F.; Asuzu, D.T.; Lorincz, A.; Bardsley, M.R.; Popko, L.N.; Choi, K.M.; Young, D.L.; Hayashi, Y.; Linden, D.R.; Kuro, M.; et al. Loss of Kitlow progenitors, reduced stem cell factor and high oxidative stress underlie gastric dysfunction in progeric mice. J. Physiol. 2010, 588, 3101–3117. [Google Scholar]
- Mitobe, M.; Yoshida, T.; Sugiura, H.; Shirota, S.; Tsuchiya, K.; Nihei, H. Oxidative stress decreases klotho expression in a mouse kidney cell line. Nephron Exp. Nephrol. 2005, 101, e67–e74. [Google Scholar] [CrossRef] [PubMed]
- Kuro, M. Klotho as a regulator of oxidative stress and senescence. Biol. Chem. 2008, 389, 233–241. [Google Scholar] [CrossRef]
- Miao, J.; Huang, J.; Luo, C.; Ye, H.; Ling, X.; Wu, Q.; Shen, W.; Zhou, L. Klotho retards renal fibrosis through targeting mitochondrial dysfunction and cellular senescence in renal tubular cells. Physiol. Rep. 2021, 9, e14696. [Google Scholar] [CrossRef]
- Sahu, A.; Mamiya, H.; Shinde, S.N.; Cheikhi, A.; Winter, L.L.; Vo, N.V.; Stolz, D.; Roginskaya, V.; Tang, W.-Y.; Croix, C.S.; et al. Age-related declines in alpha-Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration. Nat. Commun. 2018, 9, 4859. [Google Scholar] [CrossRef][Green Version]
- Tedesco, L.; Rossi, F.; Ragni, M.; Ruocco, C.; Brunetti, D.; Carruba, M.O.; Torrente, Y.; Valerio, A.; Nisoli, E. A special amino-acid formula tailored to boosting cell respiration prevents mitochondrial dysfunction and oxidative stress caused by doxorubicin in mouse cardiomyocytes. Nutrients 2020, 12, 282. [Google Scholar] [CrossRef] [PubMed][Green Version]
StD | EAAs | |
---|---|---|
KCal/Kg | 3952 | 3995 |
Carbohydrates (%) | 54.61 | 61.76 |
Lipids (%) | 7.5 | 6.12 |
Nitrogen (%) | 21.8 ° | 20 * |
Proteins: % of total N content | 95.93 | -- |
Free AA: % of total N content | 4.07 | 100 |
EAA/NEAA (% in grams) | - | 86/14 |
Free AA composition (%) | ||
l-Leucine (bcaa) | -- | 13.53 |
l-Isoleucine (bcaa) | -- | 9.65 |
l-Valine (bcaa) | -- | 9.65 |
l-Lysine | 0.97 | 11.6 |
l-Threonine | -- | 8.7 |
l-Histidine | -- | 11.6 |
l-Phenylalanine | -- | 7.73 |
l-Methionine | 0.45 | 4.35 |
l-Tyrosine | -- | 5.80 |
l-Triptophan | 0.28 | 3.38 |
l-Cystine | 0.39 | 8.20 |
l-Cysteine | -- | -- |
l-Alanine | -- | -- |
l-Glycine | 0.88 | -- |
l-Arginine | 1.1 | -- |
l-Proline | -- | -- |
l-Glutamine | -- | -- |
l-Serine | -- | 2.42 |
l-Glutamic Acid | -- | -- |
l-Asparagine | -- | -- |
l-Aspartic Acid | -- | -- |
Ornithine-αKG | -- | 2.42 |
N-acetyl-cysteine | -- | 0.97 |
Body Weight (g) | Heart Weight (g) | hw/bw (%) | |
---|---|---|---|
StD | 29.5 ± 1.41 | 0.2 ± 0.06 | 0.67 ± 0.17 |
StD + Doxo | 29.29 ± 2.29 | 0.17 ± 0.02 | 0.60 ± 0.08 |
EAAs | 28.5 ± 2 | 0.18 ± 0.01 | 0.63 ± 0.04 |
EAA + Doxo | 28.02 ± 2.4 | 0.17 ± 0.02 | 0.61 ± 0.08 |
F | 0.5 | 1.02 | 0.5 |
p | 0.687 | 0.388 | 0.690 |
Smit/Scyt (%) | Nmit/100 μ2 | Smit Mean (μ2) | |
---|---|---|---|
StD | 19.84 ± 2.37 | 32.06 ± 3.49 | 0.621 ± 0.06 |
StD + Doxo | 13.7 ± 1.57 * | 23.01 ± 3.55 * | 0.603 ± 0.09 |
EAAs | 19.75 ± 2 ^ | 34.96 ± 7.3 ^ | 0.58 ± 0.1 |
EAA + Doxo | 17.81 ± 2.14 * ^ | 29.84 ± 4.57 ° ^ | 0.612 ± 0.13 |
F | 31.72 | 16.85 | 0.48 |
p | 0.000 | 0.000 | 0.695 |
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Corsetti, G.; Romano, C.; Pasini, E.; Scarabelli, T.; Chen-Scarabelli, C.; Dioguardi, F.S. Essential Amino Acids-Rich Diet Increases Cardiomyocytes Protection in Doxorubicin-Treated Mice. Nutrients 2023, 15, 2287. https://doi.org/10.3390/nu15102287
Corsetti G, Romano C, Pasini E, Scarabelli T, Chen-Scarabelli C, Dioguardi FS. Essential Amino Acids-Rich Diet Increases Cardiomyocytes Protection in Doxorubicin-Treated Mice. Nutrients. 2023; 15(10):2287. https://doi.org/10.3390/nu15102287
Chicago/Turabian StyleCorsetti, Giovanni, Claudia Romano, Evasio Pasini, Tiziano Scarabelli, Carol Chen-Scarabelli, and Francesco S. Dioguardi. 2023. "Essential Amino Acids-Rich Diet Increases Cardiomyocytes Protection in Doxorubicin-Treated Mice" Nutrients 15, no. 10: 2287. https://doi.org/10.3390/nu15102287
APA StyleCorsetti, G., Romano, C., Pasini, E., Scarabelli, T., Chen-Scarabelli, C., & Dioguardi, F. S. (2023). Essential Amino Acids-Rich Diet Increases Cardiomyocytes Protection in Doxorubicin-Treated Mice. Nutrients, 15(10), 2287. https://doi.org/10.3390/nu15102287