Monotherapy of experimental metabolic syndrome: II. Study of cardiovascular effects

Knézl, V.; Sotníková, R; Brnoliaková, Zuzana; Stankovičová, T; Bauer, V.; Bezek, S

doi:10.1515/intox-2017-0014

Cited by 9 publications

(7 citation statements)

References 46 publications

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“…Atorvastatin produced effects comparable with SMe1EC2 in the same dosage. It reduced the total numbers of cases of sustained arrhythmia and arrhythmia in the given experiment and produced cardio-protective effects, as in previous research (23,26). Similarly to other statins, atorvastatin is thought to have many benefi cial pleiotropic effects (22,30).…”

Section: Tab 3 Occurrence Of Ventricular Arrhythmia In Animals Amonsupporting

confidence: 55%

“…Both atorvastatin and SMe1EC2 exerted cardio protective effects (22,26,31), established most probably by a complex action on numerous mechanisms affecting cell survival, signalling, oxidative and energy metabolism. In addition to lowering high cholesterol levels, atorvastatin treatment can protect patients suffering from metabolic syndrome, impaired lipid metabolism, and established cardiovascular disease from the occurrence of malignant life-threatening arrhythmia (23).…”

Section: Tab 3 Occurrence Of Ventricular Arrhythmia In Animals Amonmentioning

confidence: 99%

“…Atorvastatin is thought to provide anti-arrhythmic protection and may reduce mortality (22,23) by restoring optimal heart functions (24). Then a novel experimental drug SMe1EC2 was identifi ed to exert many benefi cial effects expressing potent anti-arrhythmic activity (25,26) with unknown action. The anti-arrhythmic activity of SMe1EC2 was here re-evaluated on a matabolic syndrome rat model to obtain additional results regarding this potential drug.…”

Section: Introductionmentioning

confidence: 99%

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Anti-arrhythmic and cardio-protective effects of atorvastatin and a potent pyridoindole derivative on isolated hearts from rats with metabolic syndrome

Lipták¹,

Knézl²,

Gaspárová³

2019

BLL

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OBJECTIVES: Aims of this study were to investigate the anti-arrhythmic and cardio-protective effect of atorvastatin and of a new pyridoindole derivative (SMe1EC2) on isolated and perfused hearts while following the Langendorff principles. BACKGROUND: Metabolic syndrome is a widely distributed condition progressing to cardiovascular disease. Many of the metabolic syndrome patients take (HMG)-co-enzyme A (CoA) reductase inhibitors with potential cardioprotective effects. SMe1EC2 is a promising new drug, exerting many positive effects in experimental settings. METHODS: Rats with induced metabolic syndrome were treated with atorvastatin (25 mg/kg) and SMe1EC2 (25 mg/kg and 0.5 mg/kg, respectively) daily for 3 weeks. After the treatment, the hearts were isolated and perfused according to Langendorff. RESULTS: Both atorvastatin and SMe1EC2 improved cardiac function by elevating the left ventricular developed pressure (VLDP) and cardiac contractility. Both SMe1EC2-treated groups improved LVDP during reperfusion, signifi cantly increased-dP/dt, and moderately elevated +dP/dt values. The treatment with both atorvastatin and SMe1EC2 (25 mg/kg) signifi cantly reduced malignant arrhythmia in comparison to control group and group treated with SMe1EC2 0.5 mg/kg. CONCLUSIONS: Owing to its anti-arrhythmic and cardio-protective effects, atorvastatin and SMe1EC2 could be of benefi t to patients suffering from metabolic syndrome (Tab.

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Section: Tab 3 Occurrence Of Ventricular Arrhythmia In Animals Amonsupporting

confidence: 55%

Section: Tab 3 Occurrence Of Ventricular Arrhythmia In Animals Amonmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anti-arrhythmic and cardio-protective effects of atorvastatin and a potent pyridoindole derivative on isolated hearts from rats with metabolic syndrome

Lipták¹,

Knézl²,

Gaspárová³

2019

BLL

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“…Therefore, drugs with anti-inflammatory and anti-oxidative properties could be a right choice for treating cardiovascular complications associated with metabolic syndrome. This occurred in results of Knezl et al ( 2017 ) who found SMe1EC2 to improve functional state of cardiovascular system of HTG rats fed with high-fat and high-cholesterol diet. In our experiments, administration of SMe1EC2 and atorvastatin significantly reduced serum levels of IL-1 and serum concentrations of TBARS.…”

Section: Discussionmentioning

confidence: 90%

Monotherapy of experimental metabolic syndrome: I. Efficacy and safety

Bezek

Brnoliaková

Sotníková

et al. 2017

Interdisciplinary Toxicology

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Elevated plasma cholesterol, especially low density lipoprotein (LDL) cholesterol, is one of the major risk factors for atherosclerosis and coronary heart disease. Hereditary hypertriglyceridemic rats (hHTG) were developed as a new inbred model for the study of relationships between blood pressure and metabolic abnormalities. The aim of this work was to determine the cholesterol-lowering and antioxidant effects of the novel pyridoindol derivative SMe1EC2, compared to the cholesterol-lowering drug atorvastatin, in rats fed either standard or high-fat and high-cholesterol diet (HFC; 1% cholesterol and 7.5% lard fat). Male hHTG rats fed HFC (HTG+HFC) were administered with SMe1EC2 or atorvastatin (both 50 mg/kg/day p.o.) for 4 weeks. Physiological status of animals was monitored by the measurement of preprandial glucose levels and blood pressure. Lipid profile was characterized by the serum levels of total cholesterol (TC), HDL-, LDL-cholesterol and triglycerides (TRG). The concentration of thiobarbituric acid reactive substances (TBARS) was evaluated in the kidney, liver and serum. Further, the assessment of pro-inflammatory cytokines TNF-α, IL-1 and IL-6 in the serum was completed. Feeding the animals with HFC diet resulted in increased serum levels of TC, LDL and TRG. SMe1EC2 ameliorated serum levels of LDL in hHTG rats, both on standard and HFC diet. These effects were comparable with those of the standard hypolipidemicum atorvastatin. SMe1EC2 lowered blood pressure, tissue TBARS concentrations and serum IL-1 levels of HTG+HFC rats. Beneficial effects together with very good toxicity profile predestinate SMe1EC2 to be promising agent for further surveys related to metabolic syndrome features.

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“…injection of 100 mg/kg ketamine and 10 mg/kg xylazine, and, in the first series, anticoagulated with heparin (500 IU i.p.). Hearts were explanted and perfused via the aorta at 80 mm Hg with a modified Krebs-Henseleit solution (Farine et al, 2016;Knezl et al, 2017) and gassed with 95% O 2 and 5% CO 2 .…”

Section: Animalsmentioning

confidence: 99%

Olanzapine-mediated cardiotoxicity is associated with altered energy metabolism in isolated rat hearts

et al. 2020

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Olanzapine is an antipsychotic drug routinely used for the treatment of schizophrenia. Although the olanzapine treatment is associated with disturbed electrical heart activity, the exact mechanism underlying this severe adverse effect remains unclear. Recently, olanzapine administration was demonstrated to be associated with elevation of blood glucose and lower levels of free fatty acids. Therefore, we investigated the effect of acute olanzapine administration on pathways regulating the cardiac energy metabolism in an isolated heart. Electrical activity and contractile parameters were recorded in isolated, spontaneously beating, adult male rat hearts, perfused with either olanzapine (100 nmol/l) or the vehicle for 10 min. Regulation of key signalling molecules was evaluated by immunoblotting and ATP levels were measured spectrophotometrically. Olanzapine prolonged the QTc intervals and induced a higher number of premature ventricular beats. Furthermore, olanzapine significantly decreased the coronary flow, the rate-pressure product and the contractility (+dP/dt and –dP/dt). These changes were associated with an increased acetyl-CoA carboxylase phosphorylation and tissue ATP levels. We also found a trend for lower phosphorylation levels of Akt and its downstream products AS160, a key regulator of GLUT4 trafficking and glycogen synthase kinase‑3ß in olanzapine‑treated hearts when compared to vehicle-treated controls. These data should contribute to the elucidation of mechanisms that underlie the adverse cardiac effects of olanzapine.

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Monotherapy of experimental metabolic syndrome: II. Study of cardiovascular effects

Cited by 9 publications

References 46 publications

Anti-arrhythmic and cardio-protective effects of atorvastatin and a potent pyridoindole derivative on isolated hearts from rats with metabolic syndrome

Anti-arrhythmic and cardio-protective effects of atorvastatin and a potent pyridoindole derivative on isolated hearts from rats with metabolic syndrome

Monotherapy of experimental metabolic syndrome: I. Efficacy and safety

Olanzapine-mediated cardiotoxicity is associated with altered energy metabolism in isolated rat hearts

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