Probiotic Lactobacillus Reuteri KUB-AC5 attenuates myocardial ischemia/reperfusion injury by mitigating cardiac mitochondrial dysfunction
C Thonusin, C Maneechote, S Chattipakorn, N ChattipakornAbstract
Background
The restoration of coronary blood flow, or called “reperfusion”, is a goal for treatment of acute myocardial infarction. Unfortunately, reperfusion commonly results in increased mortality via increased infarct size, which is defined as “myocardial ischemia/reperfusion (I/R) injury”. Probiotic Lactobacillus Reuteri KUB-AC5 has been found to exert a protective effect against obesity-induced cardiac dysfunction by ameliorating cardiac mitochondrial impairment. However, the effect of this probiotic on cardiac mitochondria in a model of myocardial I/R injury has never been determined.
Purpose
To examine the effect of probiotic Lactobacillus Reuteri KUB-AC5 on cardiac mitochondria and cardiac function in a rat model of myocardial I/R injury.
Methods
Male Wistar rats were divided into 4 groups (n=8 per group), including Sham, myocardial I/R treated with vehicle (IR), myocardial I/R treated with live form of probiotic Lactobacillus Reuteri KUB-AC5 (IRL), and myocardial I/R treated with heat-killed form of probiotic Lactobacillus Reuteri KUB-AC5 (IRH). Sham and IR groups were treated with 1 mL per day of normal saline solution as a vehicle, while IRL and IRH groups were treated with 1 x 108 colony forming unit (cfu) per day of live form and heat-killed form of Lactobacillus Reuteri KUB-AC5, respectively. All treatments were administered via oral gavage. After 12 weeks of treatment, the Sham group received sham surgery, while the other 3 groups received ligation of left anterior descending coronary artery for 30 min (ischemic period) followed by 120 min of reperfusion. Pressure-volume loop was recorded during the operation. After 120 min of reperfusion, the rats were euthanized. Cardiac tissue was then collected for mitochondrial isolation studies and infarct size analysis.
Results
The IR group exhibited left ventricular (LV) systolic dysfunction, as indicated by a reduction in LV ejection fraction, when compared to the Sham group (Fig. 1A). Regarding cardiac mitochondria, increased mitochondrial reactive oxygen species (Fig. 2A), mitochondrial membrane depolarization (Fig. 2B), and mitochondrial swelling (Fig. 2C) were found in the IR group. In addition, the IR group had decreased expressions of a mitochondrial antioxidant-related protein (SOD2) and a mitochondrial fusion-related protein (MFN2), while the expressions of a mitochondrial fission-related protein (DRP1) and a mitophagy-related protein (PINK1/parkin ratio) were increased in this group (Fig. 2D). Treatment with Lactobacillus Reuteri KUB-AC5, both live and heat-killed forms, ameliorated LV systolic dysfunction (Fig. 1A), diminished infarct area (Fig. 1B), and improved mitochondrial-related parameters (Fig. 2A-D) in the heart of rats with myocardial I/R injury.
Conclusion
Probiotic Lactobacillus Reuteri KUB-AC5, both live and heat-killed forms, alleviates myocardial I/R injury by mitigating cardiac mitochondrial dysfunction.