Cardioprotective Effect of Selective Estrogen Receptor Modulator Raloxifene Are Mediated by Heme Oxygenase in Estrogen‐Deficient Rat

Pósa, Anikó; Szabó, Renáta; Kupai, Krisztina; Berkó, A.; Veszelka, Médea; Szűcs, Gergő; Börzsei, Denise; Gyöngyösi, Mariann; Pávó, Imre; Deim, Zoltán; Szilvássy, Zoltán; Juhász, Béla; Varga, Csaba

doi:10.1155/2017/2176749

Cited by 20 publications

(20 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Surgical castration induced a significant decrease in the cardiac HO enzyme activity and HO-1 concentration in both young and aged animals, while cyproterone acetate-treated rats possessed the lowest HO values as a result of the absolute block of androgen production. Similar to estrogen replacement therapy [23], we observed a protective role of testosterone administration against oxidative damages. Exogenous testosterone-induced amelioration was effective in both young and aged animals.…”

Section: Discussionsupporting

confidence: 63%

Spotlight on a New Heme Oxygenase Pathway: Testosterone-Induced Shifts in Cardiac Oxidant/Antioxidant Status

et al. 2019

Self Cite

View full text Add to dashboard Cite

A low testosterone level contributes to the development of oxidative damages; however, the cardiovascular effects of exogenous hormone therapy are not well elucidated. The aim of our work is to study the association of the testosterone level, antioxidant/oxidant system, and anti-inflammatory status related to the heme oxygenase (HO) system. To determine the effects of testosterone, 10-week-old, and 24-month-old sham-operated and castrated male Wistar rats were used. One part of the castrated animals was daily treated with 2.5 mg/kg cyproterone acetate, while the hormone replacement therapy was performed via an i.m. injection of a dose of 8.0 mg testosterone undecanoate/kg/once a week. The plasma testosterone level, the activity of HO and myeloperoxidase (MPO) enzymes; the concentrations of the HO-1, tumor necrosis alpha (TNF-α), and cyclic guanosine monophosphate (cGMP), as well as the total level of glutathione (GSH + GSSG) were determined from the cardiac left ventricle. In accordance with the testosterone values, the aging process and castration resulted in a decrease in antioxidant HO activity, HO-1 and cGMP concentrations and in the level of GSH + GSSG, whereas the inflammatory TNF-α and MPO activity significantly increased. Testosterone therapy was able to restore the physiological values. Our results clearly show that testosterone replacement therapy increases the antioxidant status and mitigates the inflammatory parameters via the modulation of the HO system.

show abstract

Section: Discussionsupporting

confidence: 63%

Spotlight on a New Heme Oxygenase Pathway: Testosterone-Induced Shifts in Cardiac Oxidant/Antioxidant Status

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Raloxifene restores acetylcholine-induced vasodilation and attenuates vasoconstriction induced by thromboxane receptor agonist in arteries of OVX hamsters fed a cholesterol-rich diet [ 101 ]. Raloxifene also increases heme oxygenase activity and inhibits myeloperoxidase in OVX animals, promoting vasodilation and preventing elevation of the ST segment, the isoelectric period between depolarization and repolarization on the electrocardiogram, further indicating a cardioprotective role associated with antioxidant and anti-inflammatory actions [ 102 ]. Hence, SERMs can be useful for preserving endothelial function and vascular hypersensitivity in coronary arteries in patients with hypercholesterolemia or hyperlipidemia involved in MI.…”

Section: Er Modulation and Mi: Preclinical Studiesmentioning

confidence: 99%

Estrogen Receptors: Therapeutic Perspectives for the Treatment of Cardiac Dysfunction after Myocardial Infarction

Montagnoli

Rocha

et al. 2021

IJMS

View full text Add to dashboard Cite

Estrogen receptors (ER) mediate functions beyond their endocrine roles, as modulation of cardiovascular, renal, and immune systems through anti-inflammatory and anti-apoptotic effects, preventing necrosis of cardiomyocytes and endothelial cells, and attenuating cardiac hypertrophy. Estradiol (E2) prevents cardiac dysfunction, increases nitric oxide synthesis, and reduces the proliferation of vascular cells, yielding protective effects, regardless of gender. Such actions are mediated by ER (ER-alpha (ERα), ER-beta (ERβ), or G protein-coupled ER (GPER)) through genomic or non-genomic pathways, which regulate cardiovascular function and prevent tissue remodeling. Despite the extensive knowledge on the cardioprotective effects of estrogen, clinical studies conducted on myocardial infarction (MI) and cardiovascular diseases still include favorable and unfavorable profiles. The purpose of this review is to provide up-to-date information regarding molecular, preclinical, and clinical aspects of cardiovascular E2 effects and ER modulation as a potential therapeutic target for the treatment of MI-induced cardiac dysfunction.

show abstract

“…MPO-induced OxLDL peroxidation can result in reduced nitric oxide (NO) bioavailability, thereby weakening vasodilation and promotion of a pro-inflammatory state (43). Previous studies have shown that high MPO levels are associated with increased risks of cardiovascular events (44). Additionally, elevation in MPO levels as a result of leukocyte activation was negatively correlated with the tissue availability and microvascular permeability index of constitutive nitric oxide synthase (cNOS) (45).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of puerarin against burn‑induced heart injury in rats

Liu

Bai

et al. 2020

Exp Ther Med

View full text Add to dashboard Cite

The present study evaluated the potential protective effects of puerarin and its associated mechanism on burn-induced myocardial damage. A total of 40 healthy adult Wistar rats were randomly divided into four groups: i) Sham; ii) burn; iii) burn + puerarin; and iv) puerarin. Serum levels of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-6 were measured using ELISA. Myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were determined in myocardial homogenates using a commercial assay kit. TUNEL staining and western blot analysis of cleaved and pro-caspase-3 were also performed to assess apoptosis. Activation of p38-MAPK, ERK, JNK and AKT were measured using western blot analysis. Left ventricular systolic pressure, maximum rates of increase/decrease in left ventricular pressure, creatine kinase MB activity and cardiac troponin T levels were found to be altered in the burn group 12 h after burn, which were reversed by puerarin treatment. Injection of puerarin following burn injury also reduced heart water content. Serum levels of IL-1β, TNF-α and IL-6 were significantly higher in the burn group compared with those in the sham group. Puerarin treatment reduced serum levels of IL-1β, TNF-α and IL-6, in addition to reducing MPO activity and MDA levels in myocardial tissues. Puerarin inhibited the activation of caspase-3, p38, ERK and JNK following severe burn, but elevated Akt activation following severe burn. In conclusion, puerarin improved cardiac function in rats following severe burn injury, which may be due to reduced myocardial injury, inhibition of cardiomyocyte apoptosis and reduced oxidative inflammatory stress; the MAPK and AKT signaling pathways are proposed to the underlying mechanism of these findings.

show abstract

Cardioprotective Effect of Selective Estrogen Receptor Modulator Raloxifene Are Mediated by Heme Oxygenase in Estrogen‐Deficient Rat

Cited by 20 publications

References 44 publications

Spotlight on a New Heme Oxygenase Pathway: Testosterone-Induced Shifts in Cardiac Oxidant/Antioxidant Status

Spotlight on a New Heme Oxygenase Pathway: Testosterone-Induced Shifts in Cardiac Oxidant/Antioxidant Status

Estrogen Receptors: Therapeutic Perspectives for the Treatment of Cardiac Dysfunction after Myocardial Infarction

Protective effect of puerarin against burn‑induced heart injury in rats

Contact Info

Product

Resources

About