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.
- MeSH
- Antioxidants pharmacology MeSH
- Diet, High-Fat MeSH
- Fructose MeSH
- Weight Gain MeSH
- Blood Glucose metabolism MeSH
- Rats MeSH
- Metabolic Syndrome * complications drug therapy MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Metabolic syndrome (MetS) belongs to the serious health complications expanding in cardiovascular diseases, obesity, insulin resistance, and hyperglycemia. In this study, hypertriacylglycerolemic rats fed a high-fat-fructose diet (HFFD) were used as an experimental model of MetS to explore the effect of tested compounds. Effects of a new prospective pyridoindole derivative coded SMe1EC2 and the natural polyphenol rutin were tested. Endothelial nitric oxide synthase (NOS3) and nuclear factor kappa B (NF-?B) expression were assessed in the left ventricle immunohistochemically and left ventricle activity was monitored in isolated perfused rat hearts. NOS3 activity in the left ventricle decreased markedly as a result of a HFFD. NOS3 expression was upregulated by both substances. NF-?B expression was increased in the MetS group in comparison to control rats and the expression further increased in the SMe1EC2 treatment. This compound significantly improved the coronary flow in comparison to the control group during reperfusion of the heart followed after ischemia. Further, it tended to increase left ventricular systolic pressure, heart product, rate of maximal contraction and relaxation, and coronary flow during baseline assessment. Moreover, the compound SMe1EC2 decreased the sensitivity of hearts to electrically induced ventricular fibrillation. Contrary to this rutin decreased coronary flow in reperfusion. Present results suggest that despite upregulation of NOS3 by both substances tested, pyridoindole SMe1EC2 rather than rutin could be suitable in treatment strategies of cardiovascular disorders in MetS-like conditions.
- MeSH
- Biometry MeSH
- Fructose adverse effects MeSH
- Indoles pharmacology therapeutic use MeSH
- Metabolic Syndrome drug therapy enzymology etiology MeSH
- Myocardium metabolism MeSH
- NF-kappa B metabolism MeSH
- Rats, Wistar MeSH
- Drug Evaluation, Preclinical MeSH
- Pyridines pharmacology therapeutic use MeSH
- Rutin pharmacology therapeutic use MeSH
- Heart drug effects MeSH
- Nitric Oxide Synthase Type III metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH