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  2. The cardioprotection of dihydrotanshinone I against myocardial ischemia-reperfusion injury via inhibition of arachidonic acid ω-hydroxylase

The cardioprotection of dihydrotanshinone I against myocardial ischemia-reperfusion injury via inhibition of arachidonic acid ω-hydroxylase

  • Can J Physiol Pharmacol. 2016 Dec;94(12):1267-1275. doi: 10.1139/cjpp-2016-0036.
Yidan Wei 1 Meijuan Xu 1 2 Yi Ren 1 Guo Lu 1 Yangmei Xu 1 Yangyang Song 1 Hui Ji 1
Affiliations

Affiliations

  • 1 a State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, Jiangsu, China.
  • 2 b Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing, Jiangsu, China.
Abstract

Arachidonic acid (AA) is a precursor that is metabolized by several Enzymes to many biological eicosanoids. Accumulating data indicate that the ω-hydroxylation metabolite of AA, 20-hydroxyeicosatetraenoic acid (20-HETE), is considered to be involved in the myocardial ischemia-reperfusion injury (MIRI). The inhibitors of AA ω-hydroxylase, however, are demonstrated to exhibit protective effects on MIRI. Dihydrotanshinone I (DI), a bioactive constituent of danshen, is proven to be a potent inhibitor of AA ω-hydroxylase by our preliminary study in vitro. The purpose of the present study was to investigate the cardioprotection of DI against MIRI and its effects on the concentrations of 20-HETE in vivo. Rats subjected to 30 min of ischemia followed by 24 h of reperfusion were assigned to intravenously receive vehicle (sham and ischemia-reperfusion), low (1 mg/kg), middle (2 mg/kg), or high (4 mg/kg) doses of DI before reperfusion. The results demonstrated that DI treatment could improve cardiac function, reduce infarct size, ameliorate the variations in myocardial zymogram and histopathological disorders, decrease 20-HETE generation, and regulate apoptosis-related protein in myocardial ischemia-reperfusion rats. These findings suggested DI could exert considerable cardioprotective action on MIRI by the attenuation of 20-HETE generation, subsequent myocardial injury, and Apoptosis through inhibition on AA ω-hydroxylase.

Keywords

20-hydroxyeicosatetraenoic acid; acide 20-hydroxyéicosatétraénoïque; acide arachidonique; apoptose; apoptosis; arachidonic acid; danshen; dihydrotanshinone I; dommage d’ischémie–reperfusion myocardique; myocardial ischemia–reperfusion injury; ω-hydroxylase.

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