Palmitate-induced toxicity is associated with impaired mitochondrial respiration and accelerated oxidative stress in cultured cardiomyocytes: The critical role of coenzyme Q9/10

Impaired mitochondrial function concomitant to enhanced oxidative stress-induced damage are well established mechanisms involved in hyperlipidemia-induced cardiotoxicity. Currently, limited information is available on the direct effect of myocardial lipid overload on endogenous coenzyme Q9/10 (CoQ9/10) levels in association with mitochondrial respiration and oxidative stress status. Here, such effects were explored by exposing H9c2 cardiomyocytes to various doses (0.15 to 1 mM) of palmitate for 24 h. The results demonstrated that palmitate doses ≥0.25 mM are enough to impair mitochondrial respiration and cause oxidative stress. Although endogenous CoQ9/10 levels are enhanced by palmitate doses ≤0.5 mM, this is not enough to counteract oxidative stress, but is sufficient to maintain cell viability of cardiomyocytes. Palmitate doses >0.5 mM caused severe mitochondrial toxicity, including reduction of cell viability. Interestingly, enhancement of CoQ9/10 levels with the lowest dose of palmitate (0.15 mM) was accompanied by a significantly reduction of CoQ9 oxidation status, as well as low cytosolic production of reactive oxygen species. From the overall findings, it appears that CoQ9/10 response may be crucial to improve mitochondrial function in conditions linked to hyperlipidemia-induced insult. Confirmation of such findings in relevant in vivo models remains essential to better understand the cardioprotective effects in association with improving endogenous CoQ9/10 content

N-Acetyl cysteine ameliorates hyperglycemia-induced cardiomyocyte toxicity by improving mitochondrial energetics and enhancing endogenous Coenzyme Q9/10 levels

The diabetic heart has been linked with reduced endogenous levels of coenzyme Q9/10 (CoQ), an important antioxidant and component of the electron transport chain. Although CoQ has displayed cardioprotective potential in experimental models of diabetes, the impact of N-acetyl cysteine (NAC) on mitochondrial energetics and endogenous levels of CoQ remains to be clarified. To explore these effects, high glucose-exposed H9c2 cardiomyocytes were used as an experimental model of hyperglycemia-induced cardiac injury. The results showed that high glucose exposure caused an increased production of reactive oxygen species (ROS), which was associated with impaired mitochondrial energetics as confirmed by a reduction of maximal respiration rate and depleted ATP levels. These detrimental effects were consistent with significantly reduced endogenous CoQ levels and accelerated cell toxicity. Although metformin demonstrated similar effects on mitochondrial energetics and cell viability, NAC demonstrated a more pronounced effect in ameliorating cytosolic and mitochondrial ROS production. Interestingly, the ameliorative effects of NAC against hyperglycemia-induced injury were linked with its capability to enhance endogenous CoQ levels. Although such data are to be confirmed in other models, especially in vivo studies, the overall findings provide additional evidence on the therapeutic mechanisms by which NAC protects against diabetes-induced cardiac injury