Abstract
Albeit previous experiments suggest potential anti‐inflammatory effect of exogenous methane (CH4) in various organs, the mechanism of its bioactivity is not entirely understood. We aimed to investigate the potential mitochondrial effects and the underlying mechanisms of CH4 in rat cardiomyocytes and mitochondria under simulated ischaemia/reperfusion (sI/R) conditions. Three‐day‐old cultured cardiomyocytes were treated with 2.2% CH4‐artificial air mixture during 2‐hour‐long reoxygenation following 4‐hour‐long anoxia (sI/R and sI/R + CH4, n = 6‐6), with normoxic groups serving as controls (SH and SH + CH4; n = 6‐6). Mitochondrial functions were investigated with high‐resolution respirometry, and mitochondrial membrane injury was detected by cytochrome c release and apoptotic characteristics by using TUNEL staining. CH4 admixture had no effect on complex II (CII)‐linked respiration under normoxia but significantly decreased the complex I (CI)‐linked oxygen consumption. Nevertheless, addition of CH4 in the sI/R + CH4 group significantly reduced the respiratory activity of CII in contrast to CI and the CH4 treatment diminished mitochondrial H2O2 production. Substrate‐induced changes to membrane potential were partially preserved by CH4, and additionally, cytochrome c release and apoptosis of cardiomyocytes were reduced in the CH4‐treated group. In conclusion, the addition of CH4 decreases mitochondrial ROS generation via blockade of electron transport at CI and reduces anoxia‐reoxygenation‐induced mitochondrial dysfunction and cardiomyocyte injury in vitro.
Highlights
Ischaemic heart disease is a leading cause of death worldwide
Few TUNEL- positive cells were observed in the normoxia and normoxia + CH4 groups (26 ± 9% and 26.3 ± 12% of cells, respectively; P = 1.00) (Figure 3A–B,E). simulated ischaemia/reperfusion (sI/R) was accompanied by an increased TUNEL positivity (Figure 3C,E), which was diminished as a result of CH4 incubation (Figure 3D,E)
The expected mitochondrial effects of CH4 have been characterized by high-resolution respirometry (HRR), and we have shown that the administration of CH4 reduces the sI/R-related mitochondrial electron transport chain (ETC) disturbance and mitigates subsequent apoptotic consequences
Summary
Ischaemic heart disease is a leading cause of death worldwide. The underlying pathophysiology is multifactorial, but mitochondrial dysfunction, is thought to be the common denominator in ischaemia or ischaemia/reperfusion (I/R)-mediated cardiomyocyte-damaging events.[1,2]Methane (CH4) forms part of the gaseous environment, which maintains the metabolism within living aerobic cells. We took into account that CH4 can traverse cell membranes and that the molecules move down their concentration gradient into subcellular compartments.[7] Further, previous findings have demonstrated that CH4 treatment can preserve adenosine-triphosphate (ATP) production after I/R injuries to the liver and eyes.[5,6] these results strengthened the view that the mitochondrion is among the expected intracellular targets of CH4 and led us to hypothesize that increased exogenous CH4 input can influence the respiratory activity of cardiac mitochondria.[8]
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