Cardioprotective Effects of Luteolin on Ischemia/Reperfusion Injury in Diabetic Rats Are Modulated by eNOS and the Mitochondrial Permeability Transition Pathway

Abstract

Myocardial ischemia/reperfusion (I/R) injury in diabetes is associated with oxidative stress, endothelial nitric oxide synthase (eNOS) dysfunction, and mitochondrial collapse, whereas luteolin is known to protect the cardiovascular system against diabetes and I/R injury. Here, we investigated whether luteolin pretreatment diminishes myocardial I/R injury in diabetic rats by affecting eNOS and the mitochondrial permeability transition pore (mPTP). After diabetic rats were produced by streptozotocin treatment (65 mg/kg) for 3 weeks, luteolin (100 mg·kg·d) or L-NAME (25 mg·kg·d) was administered intragastrically for 2 weeks. Hearts were then isolated and subjected to 30 minutes of global ischemia followed by 120 minutes of reperfusion. Pretreatment with luteolin significantly improved left ventricular function and coronary flow throughout reperfusion, increased cardiac tissue viability and manganese superoxide dismutase (MnSOD) activity, and reduced coronary lactate dehydrogenase release, and the myocardial malonaldehyde level in diabetic I/R rat hearts. All these improving effects of luteolin were significantly attenuated by L-NAME. Luteolin also significantly upregulated eNOS expression in diabetic rat hearts after I/R. Ca-induced mPTP opening and mitochondrial inner membrane potential reduction were significantly inhibited in ventricular myocytes isolated from luteolin-treated diabetic rats, and this effect was attenuated by L-NAME. These findings indicate that luteolin protects the diabetic heart against I/R injury by upregulating the myocardial eNOS pathway, and downstream effects include the enhancement of MnSOD and inhibition of mPTP.

Luteolin‐mediated Kim‐1/NF‐kB/Nrf2 signaling pathways protects sodium fluoride‐induced hypertension and cardiovascular complications

“…Group A was the control group which was given normal saline, Group B was exposed to 300 ppm (300 mg/L) of NaF in drinking water daily for a week, Groups C and D were exposed to 300 ppm (300 mg/L) of NaF and concurrently administered Luteolin orally daily at a dosage of 100 and 200 mg/kg for the same time point. The dosage of Luteolin was chosen based on the previous studies but with slight modifications .…”

Effects of Polyphenols on Oxidative Stress-Mediated Injury in Cardiomyocytes

“…Employing diabetic rats subjected to myocardial I/R, it has been assessed the protective effects of luteolin or breviscapine, a flavonoid extracted by Erigeron breviscapus . Luteolin (100 mg/kg/day intragastrically) or breviscapine (60 mg/kg orally) reduced the ROS production [165,166]. Luteolin also improved left ventricular function and cardiac tissue viability [165].…”

“…Luteolin (100 mg/kg/day intragastrically) or breviscapine (60 mg/kg orally) reduced the ROS production [165,166]. Luteolin also improved left ventricular function and cardiac tissue viability [165]. In addition, breviscapine reduced the expression of ICAM-1 in rat myocardium, the inactivation of ATPase and associated ionic disturbances [166].…”

AT1 Receptor Modulator Attenuates the Hypercholesterolemia-Induced Impairment of the Myocardial Ischemic Post-Conditioning Benefits

“…Non-hypertensive doses of azilsartan have been reported to cardiac remodeling, infarct size and fibrotic changes after induction of myocardial infarction 28). It has been reported earlier that, eNOS dysfunction is one of the important pathways during myocardial I/R-injury 29). Wu et al4) have reported that PostC provides benefits in I/R-injury of heart by upregulation of eNOS.…”