The Effects of Isosteviol Against Myocardium Injury Induced by Ischaemia–reperfusion in the Isolated Guinea Pig Heart

Abstract

1. This study aimed to investigate the protective effects of isosteviol against myocardial ischaemia-reperfusion (IR) injury and its effects on mitochondrial adenosine triphosphate (ATP)-sensitive potassium channel (mitoK(ATP)) activity in vitro. 2. Groups of eight guinea pigs were treated as follows: constant perfusion control (PC), IR control, ischaemic preconditioning (IPC) + IR, isosteviol (50, 250 or 500 nmol) + IR, 5-hydroxydecanoate acid (5-HD) (5 micromol) + isosteviol (500 nmol) + IR. The guinea pig heart was isolated and perfused in Langendorff mode with modified Tyrode solution at a flow rate of 10 mL/min. Ischaemia was introduced for 30 min followed by reperfusion for 20 min. Cardiac function, coronary arterial flow rate, lactate dehydrogenase (LDH) and creatine kinase (CK) activities in the perfusate were measured prior to ischaemia and at the end of reperfusion. 3. There were no significant (P > 0.05) changes in cardiac function or markers of cell damage (i.e. activities of LDH and CK) in the PC group. In contrast, cardiac function was adversely affected in the IR group, with significant (P < 0.05) decreases in left ventricular developing pressure (LVDevP), dP/dt(max) and dP/dt(min) compared with baseline and the PC group. In addition, there were increases in activity of LDH (20%) and CK (67%) compared with baseline and the PC group. 4. Ischaemic preconditioning and pretreatment with isosteviol, at all dose levels, resulted in a significant (P < 0.05) attenuation of IR injury. Lactate dehydrogenase and CK activities were not significantly (P < 0.05) different compared with baseline. Isosteviol did not increase coronary flow, suggesting that the protective effect of isosteviol on the myocardium was not mediated by dilation of the coronary blood vessels. 5. Pretreatment with the mitoK(ATP) blocker 5-HD partially antagonized the effects of 500 nmol isosteviol, with a statistically significant attenuation of its protective effects on HR, LVDevP, dP/dt(max) and dP/dt(min) compared with isosteviol alone pretreatment. 6. The IR injury on the Langendorff perfused guinea pig heart was alleviated by isosteviol, which appears to mediate its effects through mitoK(ATP) channels. Future research might aim to investigate the interaction of isosteviol with mitoK(ATP) channels in order to clarify its mechanism of action.

The effect of isosteviol on hyperglycemia and dyslipidemia induced by lipotoxicity in rats fed with high-fat emulsion

“…1) is an acid hydrolysate of stevioside. We have reported that isosteviol can alleviate the injury induced by ischemia-reperfusion in isolated perfused guinea pig heart (Xu et al, 2007b), rat heart in vivo (Xu et al, 2007a) and rat brain in vivo (Xu et al, 2008). We also found that isosteviol was able to reduce plasma glucose concentrations but did not have an impact on plasma insulin levels during an intravenous glucose tolerance test in Zucker diabetic fatty rats (Ma et al, 2007).…”

The cardioprotective effect of isosteviol on rats with heart ischemia-reperfusion injury

“…This cardioprotective effect of isosteviol was similar to that of ischemia preconditioning, and was partly antagonized by a mitoK ATP channel blocker, 5-HD, suggesting that isosteviol may act as a mitoK ATP opener, to exert the protective effect (Miura et al, 2001;Xu et al, 2004). However, this effect has not been confirmed in in vivo animal models.…”

Isosteviol prevents the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels

“…Studies indicated that both stevioside and isosteviol may possess a variety of biological activities including anti-hypertension, anti-hyperglycemia, anti-inflammatory and potential antitumor effects [18][19][20][21][22]. The myocardium protective effects of isosteviol against ischemia-reperfusion (IR) injury have also been reported [23,24]. Isosteviol is proposed to be able to reduce the infraction area and restore the contractility in cardiac IR in vivo and in isolated hearts without introducing or even improving arrhythmia.…”