The activation of mitochondrial BK potassium channels contributes to the protective effects of naringenin against myocardial ischemia/reperfusion injury

Testai, Lara; Martelli, Alma; Marino, Alice; D’Antongiovanni, Vanessa; Ciregia, Federica; Giusti, Laura; Lucacchini, Antonio; Chericoni, Silvio; Breschi, Maria Cristina; Calderone, Vincenzo

doi:10.1016/j.bcp.2013.03.018

Cited by 92 publications

(92 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Naringenin promotes endothelium-independent vasorelaxing effects on rat aortic rings pre-contracted with noradrenaline (9), and is able to alleviate the myocardial ischemia/reperfusion injury (10). A previous study reported that naringenin is able to protect against doxorubicin-induced cardiac toxicity, due to its …”

Section: Discussionmentioning

confidence: 99%

“…All animals were allowed to acclimatize to the laboratory environment for 1 week, then randomly distributed to either a sham surgery or AB group, which were respectively treated without or with naringenin (normal diet containing ~100 mg/kg body weight/day naringenin) for 7 weeks, beginning 1 week after AB surgery. The dose of naringenin was administered according to the protocol described in a previous study (10). Non-naringenin (vehicle) mice received a normal diet of rodent chow.…”

Section: Methodsmentioning

confidence: 99%

“…Naringenin has been demonstrated to promote endothelium-independent vasorelaxing effects on rat aortic rings that have been precontracted with noradrenaline (9). Furthermore, naringenin may be able to alleviate myocardial ischemia/reperfusion injury (10). In addition, due to its radical-scavenging and iron-chelating properties, naringenin may potentially protect against doxorubicin-induced cardiac toxicity (6).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Naringenin attenuates pressure overload-induced cardiac hypertrophy

Zhang

Zheng

Yuan

et al. 2015

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Cardiac hypertrophy is characterized by abnormal enlargement of cardiomyocytes and disproportionate accumulation of extracellular interstitial fibrosis, which are major predictors of the development of coronary artery disease and heart failure. Naringenin is a bitter principle component of grapefruit that has numerous pharmacological effects, including anti-inflammatory, hypolipidemic, antithrombotic and antiatherogenic properties. In order to investigate whether naringenin is able to exert a protective effect against cardiac hypertrophy induced by pressure overload, aortic banding (AB) was performed to induce cardiac hypertrophy in mice, and naringenin was administered for 7 weeks. A total of 60 mice were allocated into four groups: Sham + vehicle, AB + vehicle, sham + naringenin and AB + naringenin. Naringenin treatment attenuated cardiac dysfunction, as indicated by the results of echocardiography and catheter-based measurements at 8 weeks post-surgery. The extent of cardiac hypertrophy was assessed by the heart weight/body weight, heart weight/tibial length and lung weight/body weight ratios, in addition to the cardiomyocyte cross-sectional area and the mRNA expression levels of hypertrophic maker, all of which were mitigated by naringenin administration. Naringenin also inhibited the expression of transforming growth factor-β1, connective tissue growth factor, collagen Iα and collagen IIIα, and attenuated interstitial fibrosis. In addition, naringenin downregulated the activation of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways. In conclusion, naringenin attenuated cardiac hypertrophy and interstitial fibrosis, in addition to improving left ventricular function in pressure-overloaded mice. The cardioprotective effect exerted by naringenin may be associated with the inhibition of PI3K/Akt, ERK and JNK signaling pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Naringenin attenuates pressure overload-induced cardiac hypertrophy

Zhang

Zheng

Yuan

et al. 2015

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…The experimental protocol for coronary occlusion-reperfusion was performed as described in [27], with minor modifications. Two hours before the experimental procedure, rats received an i.p.…”

Section: Acute Myocardial Infarctionmentioning

confidence: 99%

The novel H 2 S-donor 4-carboxyphenyl isothiocyanate promotes cardioprotective effects against ischemia/reperfusion injury through activation of mitoK ATP channels and reduction of oxidative stress

Testai

Marino

Piano

et al. 2016

Pharmacological Research

View full text Add to dashboard Cite

a b s t r a c tThe endogenous gasotransmitter hydrogen sulphide (H 2 S) is an important regulator of the cardiovascular system, particularly of myocardial function. Moreover, H 2 S exhibits cardioprotective activity against ischemia/reperfusion (I/R) or hypoxic injury, and is considered an important mediator of "ischemic preconditioning", through activation of mitochondrial potassium channels, reduction of oxidative stress, activation of the endogenous "anti-oxidant machinery" and limitation of inflammatory responses. Accordingly, H 2 S-donors, i.e. pro-drugs able to generate exogenous H 2 S, are viewed as promising therapeutic agents for a number of cardiovascular diseases. The novel H 2 S-donor 4-carboxy phenylisothiocyanate (4CPI), whose vasorelaxing effects were recently reported, was tested here in different experimental models of myocardial I/R.In Langendorff-perfused rat hearts subjected to I/R, 4CPI significantly improved the post-ischemic recovery of myocardial functional parameters and limited tissue injury. These effects were antagonized by 5-hydroxydecanoic acid (a blocker of mitoK ATP channels). Moreover, 4CPI inhibited the formation of reactive oxygen species. We found the whole battery of H 2 S-producing enzymes to be present in myocardial tissue: cystathionine ␥-lyase (CSE), cystathionine ␤-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (MPST). Notably, 4CPI down-regulated the post-ischemic expression of CSE.In Langendorff-perfused mouse hearts, 4CPI reduced the post-ischemic release of norepinephrine and the incidence of ventricular arrhythmias. In both rat and mouse hearts, 4CPI did not affect the degranulation of resident mast cells.In isolated rat cardiac mitochondria, 4CPI partially depolarized the mitochondrial membrane potential; this effect was antagonized by ATP (i.e., the physiological inhibitor of K ATP channels). Moreover, 4CPI abrogated calcium uptake in the mitochondrial matrix.Finally, in an in vivo model of acute myocardial infarction in rats, 4CPI significantly decreased I/Rinduced tissue injury.In conclusion, H 2 S-donors, and in particular isothiocyanate-based H2S-releasing drugs like 4CPI, can actually be considered a suitable pharmacological option in anti-ischemic therapy.

show abstract

“…The herbal plant Scutellaria baicalensis containing flavonoids (e.g., baicalein, baiclain, oroxylin A, and norwogonin) can induce preconditioning of the heart, thereby conferring a resistance to ischemiareperfusion injury (Whittenburg, 1990). Naringenin, a major flavanone in grapefruit, significantly reduced myocardial infarction heart damage by a mechanism involving activation of mitochondrial potassium channels (Testai et al, 2013). Baiclein pretreatment protected chick cardiomyocytes against ischemia/reperfusion in part by activating mitochondrial KATP channels (Chang et al, 2013).…”

Section: A Ischemia: Stroke and Myocardial Infarctionmentioning

confidence: 99%