Long-lasting disturbances in lipid and glucose metabolism present in metabolic syndrome (MetS) lead to serious cardiovascular diseases. The study was aimed to evaluate the effect of natural antioxidant vitamin E (VitE, 100 mg/kg/day, p.o.) on basal biochemical and physiological parameters characterizing MetS and on the changed function of the heart. Furthermore, the possible potentiation of VitE effect by synthetic pyridoindole antioxidant SMe1EC2 (SMe, 15 mg/kg/day, p.o.) was also tested. MetS was induced in hereditary hypertriglyceridemic rats (HTG) by the 5 weeks administration of high-fat fructose diet (HFFD: 1 % cholesterol, 7.5 % pork lard, 10 % fructose). The heart function was tested using Langendorff preparation under constant pressure. The functional parameters of isolated heart, dysrhythmias and evoked fibrillations were evaluated in conditions of ischemia-reperfusion. The HFFD increased body weight gain and serum levels of total cholesterol, low-density lipoproteins and blood glucose. The HFFD significantly increased heart flow and force of contraction, compared to standard diet (SD). During the reperfusion, the HFFD caused the increase of the ventricular premature beats number at the expense of decreasing the duration of serious dysrhythmias (ventricular tachycardias and fibrillations). The addition of VitE, SMe or their combination to the HFFD decreased body weight gain, depressed blood pressure, improved particular biochemical parameters. The combination of VitE and SMe suppressed the occurrence of serious dysrhythmias. Our data indicate that the HFFD-related disturbances led to alterations within pathophysiology in HTG rats. The results showed that a combination of antioxidants might have the potential to amend disorders accompanying MetS.

Institute of Experimental Pharmacology and Toxicology Center of Experimental Medicine Slovak Academy of Sciences Bratislava Slovak Republic

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Ahmed MH, Blaha JM, Nasir K, Rivera JJ, Blumenthal SR. Effects of physical activity on cardiovascular disease. Am J Cardiol. 2012;109:288–95. doi: 10.1016/j.amjcard.2011.08.042. PubMed DOI

de Souza MFM, Gawriszewski VP, Orduňez P, Sanhueza A, Espinal MA. Cardiovascular disease mortality in the Americas: current trends and disparities. Heart. 2012;98:1207–1212. doi: 10.1136/heartjnl-2012-301828. PubMed DOI

Mozaffarian D, Benjamin EJ, Go SA. American Heart Association Statistics Committee. Heart disease and stroke statistics - 2016 update. A report from the American Heart Association. Circulation. 2016;133:e38–e360. doi: 10.1161/CIR.0000000000000350. PubMed DOI

Fahed G, Aoun L, Bou Zerdan M, Allam S, Bou Zerdan M, Bouferraa Y, Assi HI. Metabolic syndrome: updates on pathophysiology and management in 2021. Int J Mol Sci. 2022;23:786. doi: 10.3390/ijms23020786. PubMed DOI PMC

Bayés de Luna A, Coumel P, Leclercq JF. Ambulatory sudden cardiac death: Mechanisms of production of fatal arrhythmia on the basis of data from 157 cases. Am Hearth J. 1989;117:151–159. doi: 10.1016/0002-8703(89)90670-4. PubMed DOI

Zicha J, Pechánová O, Cacányiová S, Cebová M, Kristek F, Török J, Simko F, Dobesová Z, Kunes J. Hereditary hypertriglyceridemic rat: a suitable model of cardiovascular disease and metabolic syndrome? Physiol Res. 2006;55(Suppl 1):S49–S63. doi: 10.33549/physiolres.930000.55.S1.49. PubMed DOI

Stolba P, Dobesová Z, Husek P, Opltová H, Zicha J, Vrána A, Kunes J. The hypertriglyceridemic rat as a genetic model of hypertension and diabetes. Life Sci. 1992;51:733–740. doi: 10.1016/0024-3205(92)90482-5. PubMed DOI

Kaprinay B, Lipták B, Slovák L, Švík K, Knezl V, Sotníková R, Gáspárová Z. Hypertriglyceridemic rats fed high fat diet as a model of metabolic syndrome. Physiol Res. 2016;65(Suppl 4):S515–S518. doi: 10.33549/physiolres.933524. PubMed DOI

Michalikova D, Tyukos Kaprinay B, Brnoliakova Z, Sasvariova M, Krenek P, Babiak E, Frimmel K, et al. Impact of improving eating habits and rosmarinic acid supplementation on rat vascular and neuronal system in the metabolic syndrome model. Br J Nutr. 2020;20:1–11. doi: 10.1017/S000711452000327X. PubMed DOI

McCracken E, Monaghan M, Sreenivasan S. Pathophysiology of the metabolic syndrome. Clin Dermatol. 2018;36:14–0. doi: 10.1016/j.clindermatol.2017.09.004. PubMed DOI

Lipták B, Kaprinay B, Gáspárová Z. A rat-friendly modification of the non-invasive tail-cuff to record blood pressure. Lab Animal. 2017;46:251–53. doi: 10.1038/laban.1272. PubMed DOI

Brosková Z, Knezl V. Protective effect of novel pyridoindole derivatives on ischemia/reperfusion injury of the isolated rat heart. Pharmacol Res. 2011;63:967–974. doi: 10.1016/S1734-1140(11)70612-0. PubMed DOI

Bezek Š, Brnoliaková Z, Sotníková R, Knezl V, Paulovičová E, Navarová J, Bauer V. Monotherapy of experimental metabolic syndrome: I. Efficacy and safety. Interdiscip Toxicol. 2017;10:81–85. doi: 10.1515/intox-2017-0013. PubMed DOI PMC

Knezl V, Sotnikova R, Brnoliakova Z, Stankovicova T, Bauer V, Bezek Š. Monotherapy of experimental metabolic syndrome: II. Study of cardiovascular effects. Interdiscip Toxicol. 2017;10:86–92. doi: 10.1515/intox-2017-0014. PubMed DOI PMC

Kovacikova L, Majekova M, Stefek M. Substituted pyridoindoles as biological antioxidants: drug design, chemical synthesis, and biological activity. Methods Mol Biol. 2015;1208:313–327. doi: 10.1007/978-1-4939-1441-8_23. PubMed DOI

Liptak B, Knezl V, Gasparova Z. Anti-arrhythmic and cardio-protective effects of atorvastatin and a potent pyridoindole derivative on isolated hearts from rats with metabolic syndrome. Bratisl Lek Listy. 2019;120:200–206. doi: 10.4149/BLL_2019_034. PubMed DOI

Salvaras L, Kovacic T, Janega P, Liptak B, Sasvariova M, Michalikova D, Tyukos Kaprinay B, et al. Synthetic pyridoindole and rutin affect upregulation of endothelial nitric oxide synthase and heart function in rats fed a high-fat-fructose diet. Physiol Res. 2021;70:851–863. doi: 10.33549/physiolres.934670. PubMed DOI PMC

Marková I, Malínská H, Hüttl M, Miklánková D, Oliyarnyk O, Poruba M, Rácová Z, Kazdová L, Večeřa R. The combination of atorvastatin with silymarin enhances hypolipidemic, antioxidant and anti-inflammatory effects in a rat model of metabolic syndrome. Physiol Res. 2021;70:33–43. doi: 10.33549/physiolres.934587. PubMed DOI PMC