Naringin improves post-ischemic myocardial injury by activation of KATP channels

Naringin (NRG) is a flavonoid with recognized cardioprotective effects. Then, it was investigated the cardioprotective mechanisms of NRG against ischemia-reperfusion (I/R) injury. The rats were pretreated for 7 days (v.o.) with NRG (25 mg/kg) or n-acetylcysteine (NAC, 100 mg/kg) and their isolated h...

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Veröffentlicht in:European journal of pharmacology 2023-11, Vol.958, p.176069-176069, Article 176069
Hauptverfasser: Araujo, Andreza Melo de, Cerqueira, Sandra Valeria Santos de, Menezes-Filho, José Evaldo Rodrigues de, Heimfarth, Luana, Matos, Katharina Kelly de Oliveira Gama, Mota, Karina Oliveira, Conceição, Michael Ramon de Lima, Marques, Leisiane Pereira, Roman-Campos, Danilo, Santos-Neto, Agenor Gomes dos, Albuquerque-Júnior, Ricardo Luiz Cavalcanti de, Santos, Vinícius Cisneiros de Oliveira, Vasconcelos, Carla Maria Lins de
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Sprache:eng
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Zusammenfassung:Naringin (NRG) is a flavonoid with recognized cardioprotective effects. Then, it was investigated the cardioprotective mechanisms of NRG against ischemia-reperfusion (I/R) injury. The rats were pretreated for 7 days (v.o.) with NRG (25 mg/kg) or n-acetylcysteine (NAC, 100 mg/kg) and their isolated hearts were subjected to global ischemia (30 min) and reperfusion (60 min). Furthermore, isolated hearts were perfused with 5 μM NRG in the presence of 10 μM glibenclamide (GLI) and subjected to I/R protocol. In healthy ventricular cardiomyocyte, it was evaluated the acute effect of 5 μM NRG on the GLI sensitive current. The results showed that NRG pretreatment restored the cardiac function and electrocardiogram (ECG) alterations induced by I/R injury, decreasing arrhythmia scores and the occurrence of severe arrhythmias. Lactate dehydrogenase and infarct area were decreased while superoxide dismutase (SOD), catalase and citrate synthase activities increased. Expression of SOD CuZn and SOD Mn not was altered. NRG treatment decreased reactive oxygen species (ROS) generation and lipid peroxidation without alter sulfhydryl groups and protein carbonylation. Also, NRG (5 μM) increased the glibenclamide sensitive current in isolated cardiomyocytes. In isolated heart, the cardioprotection of NRG was significantly reduced by GLI. Furthermore, NRG promoted downregulation of Bax expression and Bax/Bcl-2. Histopathological analysis showed that NRG decreased cell edema, cardiomyocytes and nucleus diameter. Thus, NRG has a cardioprotective effect against cardiac I/R injury which is mediated by its antioxidant and antiapoptotic actions and KATP channels activation. [Display omitted] •Naringin pretreatment restores cardiac function and decreases the occurrence of arrhythmia.•Naringin attenuates myocardial damage induced by ischemia-reperfusion.•Naringin decreases oxidative stress and inhibits apoptosis.•KATP channels are involved in naringin-mediated cardioprotection.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2023.176069