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Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Research Article

The Influence of Atorvastatin, Amlodipine and Ethoxidol on Ubiquinol and Ubiquinone Endogenous Plasma Concentrations in Patients with Chronic Heart Failure

Author(s): V.I. Zozina*, S.N. Kondratenko, E.V. Shikh, L.M. Krasnykh, E.S. Melnikov and V.G. Kukes

Volume 24, Issue 9, 2023

Published on: 22 September, 2023

Page: [635 - 644] Pages: 10

DOI: 10.2174/1389200224666230913133201

Price: $65

Abstract

Background: Coenzyme Q10 is a key component of the mitochondrial respiratory chain and a fat-soluble endogenous antioxidant performing many vital functions in the human body. Many researchers studied the plasma concentrations of ubiquinol, ubiquinone, total CoQ10 and the redox state (ubiquinol/ubiquinone ratio) of CoQ10 in healthy volunteers. However, these parameters in the plasma of patients with chronic heart failure (CHF) remain almost uninvestigated.

Objective: The aim of this case-control study was to investigate the effect of atorvastatin, amlodipine and ethoxidol on endogenous plasma concentrations of ubiquinol, ubiquinone, total CoQ10 and its redox state in patients with CHF.

Methods: The study included 62 patients with CHF divided into four groups depending on the prescribed therapy. For the quantitative determination of ubiquinol, ubiquinone, and total CoQ10 in the plasma of patients, HPLCMS/ MS was used.

Results: It was established that the endogenous plasma concentration of total CoQ10 in patients with CHF is significantly lower than in healthy volunteers, and the ratio of reduced and oxidized forms of CoQ10 is shifted towards ubiquinone. It was a statistically significant effect of drugs with different physicochemical structures and pharmacological action on the plasma concentrations of ubiquinol, ubiquinone and total CoQ10: atorvastatin administration led to a decrease in the concentration of ubiquinol (-33.3Δ%), and total CoQ10 (-15Δ%), administration of amlodipine contributed to an increase in the levels of ubiquinol (+27.7Δ%) and total CoQ10 (+18.2Δ%), and the administration of ethoxidol caused an increase in the concentration of ubiquinol (+25Δ%), ubiquinone (+17.7Δ%) and total CoQ10 (+20.2Δ%).

Conclusion: Amlodipine is able to neutralize the negative effect of atorvastin on the redox balance of CoQ10 in patients with CHF. An additional prescription of the antioxidant ethoxidol to standard therapy for patients with CHF was substantiated. Determination of the redox state of CoQ10 in plasma can be used to diagnose and assess the degree of oxidative stress in patients with cardiovascular diseases, as well as to assess the efficacy and safety of ongoing pharmacotherapy.

Graphical Abstract

[1]
Ernster, L.; Forsmark-Andrée, P. Ubiquinol: An endogenous antioxidant in aerobic organisms. Clin. Investig., 1993, 71(8), S60-S65.
[http://dx.doi.org/10.1007/BF00226842] [PMID: 8241707]
[2]
Littarru, G.P.; Tiano, L. Bioenergetic and antioxidant properties of coenzyme Q10: Recent developments. Mol. Biotechnol., 2007, 37(1), 31-37.
[http://dx.doi.org/10.1007/s12033-007-0052-y] [PMID: 17914161]
[3]
Belliere, J.; Devun, F.; Cottet-Rousselle, C.; Batandier, C.; Leverve, X.; Fontaine, E. Prerequisites for ubiquinone analogs to prevent mitochondrial permeability transition-induced cell death. J. Bioenerg. Biomembr., 2012, 44(1), 207-212.
[http://dx.doi.org/10.1007/s10863-012-9406-7] [PMID: 22246424]
[4]
Bhagavan, H.N.; Chopra, R.K. Plasma coenzyme Q10 response to oral ingestion of coenzyme Q10 formulations. Mitochondrion, 2007, 7, S78-S88.
[http://dx.doi.org/10.1016/j.mito.2007.03.003] [PMID: 17482886]
[5]
Bhagavan, H.N.; Chopra, R.K. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic. Res., 2006, 40(5), 445-453.
[http://dx.doi.org/10.1080/10715760600617843] [PMID: 16551570]
[6]
López-Lluch, G.; Barroso, M.P.; Martín, S.F.; Fernández-Ayala, D.J.M.; Gómez-Díaz, C.; Villalba, J.M.; Navas, P. Role of plasma membrane coenzyme Q on the regulation of apoptosis. Biofactors, 1999, 9(2-4), 171-177.
[http://dx.doi.org/10.1002/biof.5520090212] [PMID: 10416029]
[7]
Siciliano, G.; Volpi, L.; Piazza, S.; Ricci, G.; Mancuso, M.; Murri, L. Functional diagnostics in mitochondrial diseases. Biosci. Rep., 2007, 27(1-3), 53-67.
[http://dx.doi.org/10.1007/s10540-007-9037-0] [PMID: 17492503]
[8]
Zozina, V.I.; Covantev, S.; Goroshko, O.A.; Krasnykh, L.M.; Kukes, V.G. Coenzyme Q10 in cardiovascular and metabolic diseases: Current state of the problem. Curr. Cardiol. Rev., 2018, 14(3), 164-174.
[http://dx.doi.org/10.2174/1573403X14666180416115428] [PMID: 29663894]
[9]
Berman, M.; Erman, A.; Ben-Gal, T.; Dvir, D.; Georghiou, G.P.; Stamler, A.; Vered, Y.; Vidne, B.A.; Aravot, D. Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: A randomized, placebo-controlled study. Clin. Cardiol., 2004, 27(5), 295-299.
[http://dx.doi.org/10.1002/clc.4960270512] [PMID: 15188947]
[10]
Gazdík, F.; Gvozdjáková, A.; Nádvorníková, R.; Repická, L.; Jahnová, E.; Kucharská, J.; Piják, M.R.; Gazdíková, K. Decreased levels of coenzyme Q10 in patients with bronchial asthma. Allergy, 2002, 57(9), 811-814.
[http://dx.doi.org/10.1034/j.1398-9995.2002.23747.x] [PMID: 12169177]
[11]
Mancini, A.; Raimondo, S.; Di Segni, C.; Persano, M.; Gadotti, G.; Silvestrini, A.; Festa, R.; Tiano, L.; Pontecorvi, A.; Meucci, E. Thyroid hormones and antioxidant systems: Focus on oxidative stress in cardiovascular and pulmonary diseases. Int. J. Mol. Sci., 2013, 14(12), 23893-23909.
[http://dx.doi.org/10.3390/ijms141223893] [PMID: 24351864]
[12]
Deichmann, R.; Lavie, C.; Andrews, S. Coenzyme Q10 and statin-induced mitochondrial dysfunction. Ochsner J., 2010, 10(1), 16-21.
[PMID: 21603349]
[13]
Sharma, A.; Fonarow, G.C.; Butler, J.; Ezekowitz, J.A.; Felker, G.M. Coenzyme Q10 and heart failure. Circ. Heart Fail., 2016, 9(4), e002639.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.115.002639] [PMID: 27012265]
[14]
Shikh, E.; Zozina, V.; Kondratenko, S.; Melnikov, E.; Kukes, V. The particulars of certain drugs’ effect on the endogenous coenzyme Q10 plasma level in patients with cardiovascular diseases. Drug Metab. Pers. Ther., 2020, 35(2)
[PMID: 32609647]
[15]
Garrido-Maraver, J.; Cordero, M.D.; Oropesa-Ávila, M.; Fernández Vega, A.; de la Mata, M.; Delgado Pavón, A.; de Miguel, M.; Pérez Calero, C.; Villanueva Paz, M.; Cotán, D.; Sánchez-Alcázar, J.A. Coenzyme Q10 therapy. Mol. Syndromol., 2014, 5(3-4), 187-197.
[http://dx.doi.org/10.1159/000360101] [PMID: 25126052]
[16]
Mareev, V.Yu. Design and results of a prospective, randomized, double-blind study of Kudesnik; Serdecinaya Nedostatocinost, 2017, p. 17.
[17]
Moreno-Fernández, A.M.; Cordero, M.D.; Garrido-Maraver, J.; Alcocer-Gómez, E.; Casas-Barquero, N.; Carmona-López, M.I.; Sánchez-Alcázar, J.A.; de Miguel, M. Oral treatment with amitriptyline induces coenzyme Q deficiency and oxidative stress in psychiatric patients. J. Psychiatr. Res., 2012, 46(3), 341-345.
[http://dx.doi.org/10.1016/j.jpsychires.2011.11.002] [PMID: 22118833]
[18]
Testai, L.; Martelli, A.; Flori, L.; Cicero, A.F.G.; Colletti, A. Coenzyme Q10: Clinical applications beyond cardiovascular diseases. Nutrients, 2021, 13(5), 1697.
[http://dx.doi.org/10.3390/nu13051697] [PMID: 34067632]
[19]
Molyneux, S.L.; Florkowski, C.M.; George, P.M.; Pilbrow, A.P.; Frampton, C.M.; Lever, M.; Richards, A.M. Coenzyme Q10. J. Am. Coll. Cardiol., 2008, 52(18), 1435-1441.
[http://dx.doi.org/10.1016/j.jacc.2008.07.044] [PMID: 19017509]
[20]
Shimizu, M.; Miyazaki, T.; Takagi, A.; Sugita, Y.; Ouchi, S.; Aikawa, T.; Shiozawa, T.; Hiki, M.; Takahashi, S.; Hiki, M.; Shimada, K.; Daida, H. Low coenzyme Q10 levels in patients with acute cardiovascular disease are associated with long-term mortality. Heart Vessels, 2021, 36(3), 401-407.
[http://dx.doi.org/10.1007/s00380-020-01698-7] [PMID: 32939561]
[21]
Kalenikova, E.I.; Kharitonova, E.V.; Gorodetskaya, E.A.; Tokareva, O.G.; Medvedev, O.S. HPLC estimation of coenzyme Q10 redox status in plasma after intravenous coenzyme Q10 administration. Biomed. Khim., 2015, 61(1), 125-131.
[http://dx.doi.org/10.18097/PBMC20156101125] [PMID: 25762606]
[22]
Littaru, G.P.; Ho, L.; Folkers, K. Deficiency of coenzyme Q 10 in human heart disease. I. Int. J. Vitam. Nutr. Res., 1972, 42(2), 291-305.
[PMID: 5053855]
[23]
Belardinelli, R.; Muçaj, A.; Lacalaprice, F.; Solenghi, M.; Principi, F.; Tiano, L.; Littarru, G.P. Coenzyme Q 10 improves contractility of dysfunctional myocardium in chronic heart failure. Biofactors, 2005, 25(1-4), 137-145.
[http://dx.doi.org/10.1002/biof.5520250115] [PMID: 16873938]
[24]
Zozina, V.I.; Melnikov, E.S.; Krasnykh, L.M.; Goroshko, O.A.; Kukes, V.G. The impact of cardiovascular and bronchopulmonary diseases on Coenzyme Q10 plasma concentration. Sechenov Med. J., 2019, 10(1), 16-21.
[http://dx.doi.org/10.47093/22187332.2019.1.16-21]
[25]
Ayer, A.; Macdonald, P.; Stocker, R. CoQ 10 function and role in heart failure and ischemic heart disease. Annu. Rev. Nutr., 2015, 35(1), 175-213.
[http://dx.doi.org/10.1146/annurev-nutr-071714-034258] [PMID: 25974695]
[26]
Cocchi, M.N.; Giberson, B.; Berg, K.; Salciccioli, J.D.; Naini, A.; Buettner, C.; Akuthota, P.; Gautam, S.; Donnino, M.W. Coenzyme Q10 levels are low and associated with increased mortality in post-cardiac arrest patients. Resuscitation, 2012, 83(8), 991-995.
[http://dx.doi.org/10.1016/j.resuscitation.2012.03.023] [PMID: 22465806]
[27]
Quinzii, C.M.; López, L.C.; Von-Moltke, J.; Naini, A.; Krishna, S.; Schuelke, M.; Salviati, L.; Navas, P.; DiMauro, S.; Hirano, M. Respiratory chain dysfunction and oxidative stress correlate with severity of primary CoQ 10 deficiency. FASEB J., 2008, 22(6), 1874-1885.
[http://dx.doi.org/10.1096/fj.07-100149] [PMID: 18230681]
[28]
Wada, H.; Hagiwara, S.I.; Saitoh, E.; Ieki, R.; Okamura, T.; Ota, T.; Iguchi, M.; Yuasa, K.; Kodaka, T.; Koishi, T.; Yamamoto, Y.; Goto, H. Increased oxidative stress in patients with chronic obstructive pulmonary disease (COPD) as measured by redox status of plasma coenzyme Q10. Pathophysiology, 2006, 13(1), 29-33.
[http://dx.doi.org/10.1016/j.pathophys.2005.09.014] [PMID: 16289557]
[29]
Zozina, V.I.; Shikh, E.V.; Kondratenko, S.N.; Melnikov, E.S.; Kukes, V.G. The effect of coenzyme Q10 as a part of standard therapy on plasma concentrations of ubiquinol, ubiquinone, total CoQ10 and its redox state in patients with ischemic heart disease. Curr. Drug Metab., 2022, 23(12), 991-999.
[http://dx.doi.org/10.2174/1389200224666221123092256] [PMID: 36420876]
[30]
Gutierrez-Mariscal, F.M.; Arenas-de Larriva, A.P.; Limia-Perez, L.; Romero-Cabrera, J.L.; Yubero-Serrano, E.M.; López-Miranda, J. Coenzyme Q10 supplementation for the reduction of oxidative stress: Clinical implications in the treatment of chronic diseases. Int. J. Mol. Sci., 2020, 21(21), 7870.
[http://dx.doi.org/10.3390/ijms21217870] [PMID: 33114148]
[31]
Yamamoto, Y.; Yamashita, S. Plasma ratio of ubiquinol and ubiquinone as a marker of oxidative stress. Mol. Aspects Med., 1997, 18, 79-84.
[http://dx.doi.org/10.1016/S0098-2997(97)00007-1] [PMID: 9266509]
[32]
Botelho, A.F.M.; Lempek, M.R.; Branco, S.E.M.T.; Nogueira, M.M.; de Almeida, M.E.; Costa, A.G.; Freitas, T.G.; Rocha, M.C.R.C.; Moreira, M.V.L.; Barreto, T.O.; Santos, J.C.; Lavalle, G.; Melo, M.M. Coenzyme Q10 cardioprotective effects against doxorubicin-induced cardiotoxicity in wistar rat. Cardiovasc. Toxicol., 2020, 20(3), 222-234.
[http://dx.doi.org/10.1007/s12012-019-09547-4] [PMID: 31435888]
[33]
DiNicolantonio, J.J.; Bhutani, J.; McCarty, M.F.; O’Keefe, J.H. Coenzyme Q10 for the treatment of heart failure: A review of the literature. Open Heart, 2015, 2(1), e000326.
[http://dx.doi.org/10.1136/openhrt-2015-000326] [PMID: 26512330]
[34]
Khan, N.A.; Abid, M.; Ahmad, A.; Abuzinadah, M.F.; Basheikh, M.; Kishore, K. Cardioprotective effect of coenzyme Q10 on apoptotic myocardial cell death by regulation of Bcl-2 gene expression. J. Pharmacol. Pharmacother., 2017, 8(3), 122-127.
[PMID: 29081620]
[35]
Yamamoto, Y.; Yamashita, S. Ubiquinol/ubiquinone ratio as a marker of oxidative stress. Methods Mol. Biol., 2002, 186, 241-246.
[http://dx.doi.org/10.1385/1-59259-173-6:241] [PMID: 12013772]
[36]
Cirilli, I.; Damiani, E.; Dludla, P.V.; Hargreaves, I.; Marcheggiani, F.; Millichap, L.E.; Orlando, P.; Silvestri, S.; Tiano, L. Role of coenzyme Q10 in health and disease: An update on the last 10 Years (2010-2020). Antioxidants, 2021, 10(8), 1325.
[http://dx.doi.org/10.3390/antiox10081325] [PMID: 34439573]
[37]
Flowers, N.; Hartley, L.; Todkill, D.; Stranges, S.; Rees, K. Co-enzyme Q10 supplementation for the primary prevention of cardiovascular disease. Cochrane Libr., 2014, 2014(12), CD010405.
[http://dx.doi.org/10.1002/14651858.CD010405.pub2] [PMID: 25474484]
[38]
Gutierrez-Mariscal, F.M.; de la Cruz-Ares, S.; Torres-Peña, J.D.; Alcalá-Diaz, J.F.; Yubero-Serrano, E.M.; López-Miranda, J. Coenzyme Q10 and cardiovascular diseases. Antioxidants, 2021, 10(6), 906.
[http://dx.doi.org/10.3390/antiox10060906] [PMID: 34205085]
[39]
Keogh, A.; Fenton, S.; Leslie, C.; Aboyoun, C.; Macdonald, P.; Bailey, M.; Rosenfeldt, F.; Rosenfeldt, F. Randomised double-blind, placebo-controlled trial of coenzyme Q10 therapy in class II and III systolic heart failure. Heart Lung Circ., 2003, 12(3), 135-141.
[http://dx.doi.org/10.1046/j.1443-9506.2003.00189.x] [PMID: 18705154]
[40]
Ulla, A.; Mohamed, M.K.; Sikder, B.; Rahman, A.F.M.T.; Sumi, F.A.; Hossain, M.; Reza, H.M.; Rahman, G.M.S.; Alam, M.A. Coenzyme Q10 prevents oxidative stress and fibrosis in isoprenaline induced cardiac remodeling in aged rats. BMC Pharmacol. Toxicol., 2017, 18(1), 29.
[http://dx.doi.org/10.1186/s40360-017-0136-7] [PMID: 28427467]
[41]
Hermida, N.; Michel, L.; Esfahani, H.; Dubois-Deruy, E.; Hammond, J.; Bouzin, C.; Markl, A.; Colin, H.; Steenbergen, A.V.; De Meester, C.; Beauloye, C.; Horman, S.; Yin, X.; Mayr, M.; Balligand, J.L. Cardiac myocyte β3-adrenergic receptors prevent myocardial fibrosis by modulating oxidant stress-dependent paracrine signaling. Eur. Heart J., 2018, 39(10), 888-898.
[http://dx.doi.org/10.1093/eurheartj/ehx366] [PMID: 29106524]
[42]
Götz, M.E.; Gerstner, A.; Harth, R.; Dirr, A.; Janetzky, B.; Kuhn, W.; Riederer, P.; Gerlach, M. Altered redox state of platelet coenzyme Q 10 in Parkinson’s disease. J. Neural Transm., 2000, 107(1), 41-48.
[http://dx.doi.org/10.1007/s007020050003] [PMID: 10809402]
[43]
ЕМА Guideline on bioanalytical method validation. 2011. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-bioanalytical-method-validation_en.pdf
[44]
Krasnykh, L.M.; Zozina, V.I.; Mel’nikov, E.S.; Goroshko, O.A.; Rodina, T.A.; Vasilenko, G.F.; Kukes, V.G. Quantitative determination of ubiquinone and ubiquinol in blood plasma by HPLC with mass-spectrometric detection. Pharm. Chem. J., 2022, 56(7), 994-998.
[http://dx.doi.org/10.1007/s11094-022-02739-3]
[45]
Zozina, V.I.; Melnikov, E.S.; Goroshko, O.A.; Krasnykh, L.M.; Kukes, V.G. Analytical method development for CoQ10 determination in human plasma using HPLC-UV and HPLC/MS/MS. Curr. Pharm. Anal., 2019, 15(7), 795-807.
[http://dx.doi.org/10.2174/1573412915666190328215854]
[46]
FDA Guidance for IndustryBioanalytical method validation (draft guidance); U.S. Government Printing Office: Washington, DC, 2013.
[47]
Rules for conducting studies on the bioequivalence of medicinal products within the framework of the Eurasian Economic Union 2016. Available from:https://docs.cntd.ru/document/456026107
[48]
Bondareva, I.B.; Bunyatyan, N.D.; Jerdev, V.P. Methodical Instructions: Assessment of Bioequivalence of medicinal products; , 2008. Available from:http://fptl.ru/biblioteka/razrabotka-i-ekspertiza-LS/ocenka-biojekvivalentnosti-lekarstvennyh-sredstv_2008.pdf
[49]
Romuk, E.; Wojciechowska, C. Jacheć W.; Nowak, J.; Niedziela, J.; Malinowska-Borowska, J.; Głogowska-Gruszka, A.; Birkner, E.; Rozentryt, P. Comparison of oxidative stress parameters in heart failure patients depending on ischaemic or nonischaemic aetiology. Oxid. Med. Cell. Longev., 2019, 2019, 1-13.
[http://dx.doi.org/10.1155/2019/7156038] [PMID: 31636808]
[50]
Wang, B.; Shi, Z.; Weber, G.F.; Kennedy, M.A. Introduction of a new critical p value correction method for statistical significance analysis of metabonomics data. Anal. Bioanal. Chem., 2013, 405(26), 8419-8429.
[http://dx.doi.org/10.1007/s00216-013-7284-4] [PMID: 24026514]
[51]
Miles, M.V.; Horn, P.S.; Tang, P.H.; Morrison, J.A.; Miles, L.; DeGrauw, T.; Pesce, A.J. Age-related changes in plasma coenzyme Q10 concentrations and redox state in apparently healthy children and adults. Clin. Chim. Acta, 2004, 347(1-2), 139-144.
[http://dx.doi.org/10.1016/j.cccn.2004.04.003] [PMID: 15313151]
[52]
Niklowitz, P.; Onur, S.; Fischer, A.; Laudes, M.; Palussen, M.; Menke, T.; Döring, F. Coenzyme Q10 serum concentration and redox status in European adults: Influence of age, sex, and lipoprotein concentration. J. Clin. Biochem. Nutr., 2016, 58(3), 240-245.
[http://dx.doi.org/10.3164/jcbn.15-73] [PMID: 27257350]
[53]
Khatta, M.; Alexander, B.S.; Krichten, C.M.; Fisher, M.L.; Freudenberger, R.; Robinson, S.W.; Gottlieb, S.S. The effect of coenzyme Q10 in patients with congestive heart failure. Ann. Intern. Med., 2000, 132(8), 636-640.
[http://dx.doi.org/10.7326/0003-4819-132-8-200004180-00006] [PMID: 10766682]
[54]
Hasanloei, M.A.V.; Zeinaly, A.; Rahimlou, M.; Houshyar, H.; Moonesirad, S.; Hashemi, R. Effect of coenzyme Q10 supplementation on oxidative stress and clinical outcomes in patients with low levels of coenzyme Q10 admitted to the intensive care unit. J. Nutr. Sci., 2021, 10, e48.
[http://dx.doi.org/10.1017/jns.2021.39] [PMID: 34290862]
[55]
Rundek, T.; Naini, A.; Sacco, R.; Coates, K.; DiMauro, S. Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke. Arch. Neurol., 2004, 61(6), 889-892.
[http://dx.doi.org/10.1001/archneur.61.6.889] [PMID: 15210526]
[56]
Stancu, C.; Sima, A. Statins: Mechanism of action and effects. J. Cell. Mol. Med., 2001, 5(4), 378-387.
[http://dx.doi.org/10.1111/j.1582-4934.2001.tb00172.x] [PMID: 12067471]
[57]
Hool, L.; Dimaria, C.; Viola, H.; Arthur, P. Role of NAD(P)H oxidase in the regulation of cardiac L-type Ca channel function during acute hypoxia. Cardiovasc. Res., 2005, 67(4), 624-635.
[http://dx.doi.org/10.1016/j.cardiores.2005.04.025] [PMID: 15913584]
[58]
Kukes, V.S.E.; Zhestovskaia, A.; Pavlova, L.; Goroshko, O. Vlijanie etilmetilgidroksipiridina malata na metabolicheskuju funkciju pecheni u pacientov s razlichnymi funkcional’nymi klassami hronicheskoj serdechnoj nedostatochnosti. Med. News North Caucasus., 2018, 3(1), 5-7.

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