Impact of thyroid hormones and grape juice on biochemical markers and metabolic control proteins in experimental pulmonary arterial hypertension
DOI:
https://doi.org/10.1590/Keywords:
PGC-1-alpha, Pyruvate dehydrogenase, Monocrotaline, Food intakeAbstract
Background-Pulmonary arterial hypertension (PAH) increases afterload in the right ventricle (RV), inducing adverse ventricular remodelling. Objective- This study explored the protective effects of thyroid hormones and grape juice on serum biomarkers and proteins related to intermediary metabolism in the RV in a model of PAH. Methods- PAH was induced in Wistar rats via the administration of monocrotaline (60 mg/kg i.p.) and they were subsequently treated with organic grape juice (GJ) and thyroid hormones (TH), administered separately or in combination. Results: The RV systolic diameter significantly increased (20%) in the PAH group compared to the control group (P = 0.002). Total CK, LDH, and ALT levels were reduced (~50%) (P<0.001) in the PAH+TH+GJ group as compared to PAH group. Glucose, albumin, triglyceride, and total cholesterol levels were reduced (~50%) (P<0.001) in the PAH group; however, these parameters returned to baseline in the PAH+GJ group. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) protein expression increased two-fold (P<0.001) and PDH protein levels were reduced (~25%) in the PAH+TH+GJ group compared to the PAH group (P<0.001). Conclusion: The data suggest that serum biomarkers can help in the evaluation of this disease, and that this therapeutic approach can attenuate maladaptive remodelling in the PAH model.
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Albuquerque B, Chen X, Hirenallur-Shanthappa D, Zhao Y, Stansfield JC, Zhang BB, et al. Neutralization of GDF15 Prevents Anorexia and Weight Loss in the Monocrotaline-Induced Cardiac Cachexia Rat Model. Cells. 2022; 11(7): 1–10.
Al Husseini A, Bagnato G, Farkas L, Gomez-Arroyo J, Farkas D, Mizuno S, et al. Thyroid hormone is highly permissive in angioproliferative pulmonary hypertension in rats. Eur Respir J. 2013 Jan; 41(1): 104-14. doi: 10.1183/09031936.00196511. Epub 2012 Jul 26. PMID: 22835607.
» https://doi.org/10.1183/09031936.00196511.
Arques S, Ambrosi P. Human serum albumin in the clinical syndrome of heart failure. J Card Fail. 2011; 17(6): 451–8.
Bernal-Ramírez J, Silva-Platas C, Jerjes-Sánchez C, Ramos- González MR, Vázquez-Garza E, Chapoy-Villanueva H, et al. Resveratrol Prevents Right Ventricle Dysfunction, Calcium Mishandling, and Energetic Failure via SIRT3 Stimulation in Pulmonary Arterial Hypertension. Oxid Med Cell Longev. 2021; 15.
Bertero E, Maack C. Metabolic remodelling in heart failure. Nat Rev Cardiol. 2018; 15(8): 457–70.
Corssac GB, De Castro AL, Tavares AV, Campos C, Fernandes RO, Ortiz VD, et al. Thyroid hormones effects on oxidative stress and cardiac remodeling in the right ventricle of infarcted rats. Life Sci. 2016;146:109–16.
Dani C, Pasquali MAB, Oliveira MR, Umezu FM, Salvador M, Henriques JAP, et al. Protective effects of purple grape juice on carbon tetrachloride-induced oxidative stress in brains of adult Wistar rats. J Med Food. 2008;11(1).
De Castro AL, Tavares AV, Campos C, Fernandes RO, Siqueira R, Conzatti A, et al. Cardioprotective effects of thyroid hormones in a rat model of myocardial infarction are associated with oxidative stress reduction. Mol Cell Endocrinol. 2014; 391(1–2): 22–9.
Dos Santos Lacerda D, Türck P, Gazzi de Lima-Seolin B, Colombo R, Duarte Ortiz V, Poletto Bonetto JH, et al. Pterostilbene reduces oxidative stress, prevents hypertrophy and preserves systolic function of right ventricle in cor pulmonale model. Br J Pharmacol. 2017 Oct; 174(19): 3302-3314. doi: 10.1111/bph.13948. Epub 2017 Aug 14. PMID: 28703274; PMCID: PMC5595755.
» https://doi.org/10.1111/bph.13948.
Huber LC, Bye H, Brock M. The pathogenesis of pulmonary hypertension - An update. Swiss Med Wkly. 2015; 145(October): 1–8.
Inampudi C, Tedford RJ, Hemnes AR, Hansmann G, Bogaard H, Koestenberger M, et al. Tratamento da disfunção ventricular direita e insuficiência cardíaca na hipertensão arterial pulmonar Abstrato. Cardiovasc Diagn Ther. 2020; 10(5): 1659–74.
Jankauskas SS, Morelli MB, Gambardella J, Lombardi A, Santulli G. Thyroid hormones regulate both cardiovascular and renal mechanisms underlying hypertension. J Clin Hypertens. 2021; 23(2): 373–81.
Klein D, Kern RM, Sokol RZ. A method for quantification and correction of proteins after transfer to immobilization membranes. Biochem Mol Biol Int. 1995; 36(1): 59–66.
Komolafe O, Pereira SP, Davidson BR, Gurusamy KS. Serum C-reactive protein, procalcitonin, and lactate dehydrogenase for the diagnosis of pancreatic necrosis. Cochrane Database Syst Rev. 2017; (4): CDO12645.
Liang H, Ward WF. PGC-1α: A key regulator of energy metabolism. Am J Physiol - Adv Physiol Educ. 2006; 30(4): 145–51.
Maleki SJ, Crespo JF, Cabanillas B. Anti-inflammatory effects of flavonoids. Food Chem. 2019; 299: 125124.
Nakai G, Shimura D, Uesugi K, Kajimura I, Jiao Q, Kusakari Y, et al. Pyruvate dehydrogenase activation precedes the down-regulation of fatty acid oxidation in monocrotaline-induced myocardial toxicity in mice. Heart Vessels. 2019; 34(3): 545–55.
Parsanathan R, Jain SK. Novel Invasive and Noninvasive Cardiac-Specific Biomarkers in Obesity and Cardiovascular Diseases. Metab Syndr Relat Disord. 2020; 18(1): 10–30.
Paulin R, Michelakis ED. The metabolic theory of pulmonary arterial hypertension. Circ Res. 2014; 115(1): 148–64.
Penedo-Vázques A, Duran X, Mateu J, López-Postigo A, Barreiro E. Curcumin and Resveratrol Improve Muscle Function and Structure through attenuation of proteolytic markers in experimental cancer-induced cachexia. Molecules. 2021;26:4904.
Olivares EL, Marassi MP, Fortunato RS, da Silva AC, Costa-e-Sousa RH, Araújo IG, et al. Thyroid function disturbance and type 3 iodothyronine deiodinase induction after myocardial infarction in rats a time course study. Endocrinology. 2007 Oct; 148(10): 4786-92. doi: 10.1210/en.2007-0043. Epub 2007 Jul 12. PMID: 17628010.
» https://doi.org/10.1210/en.2007-0043.
Rasines-Perea Z, Teissedre PL. Grape Polyphenols’ effects in human cardiovascular diseases and diabetes. Molecules. 2017; 22(1): 1–19.
Singal PK, Khaper N, Farahmand F, Belló-Klein A. Oxidative stress in congestive heart failure. Curr Cardiol Rep. 2000; 2(3): 206–11.
Spyropoulos F, Michael Z, Finander B, Vitali S, Kosmas K, Zymaris P, et al. Acetazolamide Improves Right Ventricular Function and Metabolic Gene Dysregulation in Experimental Pulmonary Arterial Hypertension. Front Cardiovasc Med. 2021; 8(June): 1–12.
Türck P, Salvador IS, Campos-Carraro C, Ortiz V, Bahr A, Andrades M, et al. Blueberry extract improves redox balance and functional parameters in the right ventricle from rats with pulmonary arterial hypertension. Eur J Nutr. 2022 Feb; 61(1): 373-386. doi: 10.1007/s00394-021-02642-9. Epub 2021 Aug 10. PMID: 34374852.
» https://doi.org/10.1007/s00394-021-02642-9.
Vinke P, Jansen SM, Witkamp RF, van Norren K. Increasing quality of life in pulmonary arterial hypertension: is there a role for nutrition? Heart Fail Rev. 2018; 23(5): 711–22.
Vrigkou E, Vassilatou E, Dima E, Langleben D, Kotanidou A, Tzanela M. The Role of Thyroid Disorders, Obesity, Diabetes Mellitus and Estrogen Exposure as Potential Modifiers for Pulmonary Hypertension. J Clin Med. 2022 Feb 10; 11(4): 921. doi: 10.3390/jcm11040921. PMID: 35207198; PMCID: PMC8874474.
» https://doi.org/10.3390/jcm11040921.
Zimmer A, Teixeira RB, Constantin RL, Campos-Carraro C, Aparicio Cordero EA, Ortiz VD, et al. The progression of pulmonary arterial hypertension induced by monocrotaline is characterized by lung nitrosative and oxidative stress, and impaired pulmonary artery reactivity. Eur J Pharmacol. 2021; 891(May 2020): 173699.
Zimmer A, Teixeira RB, Bonetto JHP, Bahr AC, Türck P, de Castro AL, et al. Role of inflammation, oxidative stress, and autonomic nervous system activation during the development of right and left cardiac remodeling in experimental pulmonary arterial hypertension. Mol Cell Biochem. 2020; 464(1–2): 93–109.
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