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Isosteviol prevents the development of isoprenaline?induced myocardial hypertrophy.

ABSTRACT: Isosteviol sodium (STVNa), which is a derivate of the natural sweet?tasting glycoside stevioside, has recently been developed and it has been determined that this compound exhibits neuro? and cardio?protective properties. In the current study, whether STVNa interferes with the development of cardiac hypertrophy, which is induced by isoprenaline (Iso), was investigated in an experimental rat model. Rats were treated with a vehicle (0.9% NaCl; control), isoprenaline (Iso; 5 mg/kg) or Iso (5 mg/kg) with STVNa (4 mg/kg; Iso + STVNa). Cardiomyocytes were isolated using enzymatic dissociation and were treated with 5 µM Iso for 24 h and co?treated with 5 µM STVNa. Brain natriuretic peptide (BNP) mRNA expression was determined using PCR analysis. Cell surface area, intracellular reactive oxygen species (ROS), mitochondrial transmembrane potential (??m), cytoplasmic Ca2+ and Ca2+ and contractile function were examined using a laser scanning confocal microscope. The current study demonstrated that STVNa inhibited Iso?induced cardiac hypertrophy by inhibiting cardiomyocyte size. STVNa significantly reduced cell surface area and decreased BNP mRNA expression in ventricular cardiomyocyte Iso?induced hypertrophy. STVNa was also revealed to restore ??m and reduce ROS generation and intracellular Ca2+ concentration when compared with the Iso?treated group. Additionally, STVNa preserved Ca2+ transients in hypertrophic cardiomyocytes. In conclusion, the present study demonstrated that STVNa protects against Iso?induced myocardial hypertrophy by reducing oxidative stress, restoring ??m and maintaining Ca2+ homeostasis.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6777692 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Isosteviol prevents the development of isoprenaline‑induced myocardial hypertrophy.

Chen Yaoxu Y Beng Huimin H Su Hao H Han Fuping F Fan Zhuo Z Lv Nanying N Jovanović Aleksandar A Tan Wen W

International journal of molecular medicine 20190917 5

Isosteviol sodium (STVNa), which is a derivate of the natural sweet‑tasting glycoside stevioside, has recently been developed and it has been determined that this compound exhibits neuro‑ and cardio‑protective properties. In the current study, whether STVNa interferes with the development of cardiac hypertrophy, which is induced by isoprenaline (Iso), was investigated in an experimental rat model. Rats were treated with a vehicle (0.9% NaCl; control), isoprenaline (Iso; 5 mg/kg) or Iso (5 mg/kg) ...[more]

PMID: 31545484

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Project description:BACKGROUND:Empagliflozin showed efficacy in controlling glycaemia, leading to reductions in HbA1c levels, weight loss and blood pressure, compared to standard treatment. Moreover, the EMPA-REG OUTCOME trial demonstrated a 14% reduction of major adverse cardiovascular events (MACE), a 38% reduction in cardiovascular (CV) death and a 35% reduction in the hospitalization rate for heart failure (HF). These beneficial effect on HF were apparently independent from glucose control. However, no mechanistic in vivo studies are available to explain these results, yet. We aimed to determine the effect of empagliflozin on left ventricular (LV) function in a mouse model of doxorubicin-induced cardiomyopathy (DOX-HF). METHODS:Male C57Bl/6 mice were randomly assigned to the following groups: controls (CTRL, n?=?7), doxorubicin (DOX, n?=?14), DOX plus empagliflozin (DOX?+?EMPA, n?=?14), or DOX plus furosemide (DOX?+?FURO group, n?=?7). DOX was injected intraperitoneally. LV function was evaluated at baseline and after 6 weeks of treatment using high-resolution echocardiography with 2D speckle tracking (Vevo 2100). Histological assessment was obtained using Haematoxylin and Eosin and Masson's Goldner staining. RESULTS:A significant decrease in both systolic and diastolic LV function was observed after 6 weeks of treatment with doxorubicin. EF dropped by 32% (p?=?0.002), while the LS was reduced by 42% (p?<?0.001) and the CS by 50% (p?<?0.001). However, LV function was significantly better in the DOX?+?EMPA group, both in terms of EF (61.30?±?11% vs. 49.24?±?8%, p?=?0.007), LS (- 17.52?±?3% vs. - 13.93?±?5%, p?=?0.04) and CS (- 25.75?±?6% vs. - 15.91?±?6%, p?<?0.001). Those results were not duplicated in the DOX?+?FURO group. Hearts from the DOX?+?EMPA group showed a 50% lower degree of myocardial fibrosis, compared to DOX mice (p?=?0.03). No significant differences were found between the DOX?+?FURO and the DOX group (p?=?0.103). CONCLUSION:Empagliflozin attenuates the cardiotoxic effects exerted by doxorubicin on LV function and remodelling in nondiabetic mice, independently of glycaemic control. These findings support the design of clinical studies to assess their relevance in a clinical setting.

Dataset Information

Isosteviol prevents the development of isoprenaline?induced myocardial hypertrophy.

Publications

Isosteviol prevents the development of isoprenaline‑induced myocardial hypertrophy.

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