L-Carnitine: An Antioxidant Remedy for the Survival of Cardiomyocytes under Hyperglycemic Condition

Abstract

Background Metabolic alterations as hyperglycemia and inflammation induce myocardial molecular events enhancing oxidative stress and mitochondrial dysfunction. Those alterations are responsible for a progressive loss of cardiomyocytes, cardiac stem cells, and consequent cardiovascular complications. Currently, there are no effective pharmacological measures to protect the heart from these metabolic modifications, and the development of new therapeutic approaches, focused on improvement of the oxidative stress condition, is pivotal. The protective effects of levocarnitine (LC) in patients with ischemic heart disease are related to the attenuation of oxidative stress, but LC mechanisms have yet to be fully understood. Objective The aim of this work was to investigate LC's role in oxidative stress condition, on ROS production and mitochondrial detoxifying function in H9c2 rat cardiomyocytes during hyperglycemia. Methods H9c2 cells in the hyperglycemic state (25 mmol/L glucose) were exposed to 0.5 or 5 mM LC for 48 and 72 h: LC effects on signaling pathways involved in oxidative stress condition were studied by Western blot and immunofluorescence analysis. To evaluate ROS production, H9c2 cells were exposed to H2O2 after LC pretreatment. Results Our in vitro study indicates how LC supplementation might protect cardiomyocytes from oxidative stress-related damage, preventing ROS formation and activating antioxidant signaling pathways in hyperglycemic conditions. In particular, LC promotes STAT3 activation and significantly increases the expression of antioxidant protein SOD2. Hyperglycemic cardiac cells are characterized by impairment in mitochondrial dysfunction and the CaMKII signal: LC promotes CaMKII expression and activation and enhancement of AMPK protein synthesis. Our results suggest that LC might ameliorate metabolic aspects of hyperglycemic cardiac cells. Finally, LC doses herein used did not modify H9c2 growth rate and viability. Conclusions Our novel study demonstrates that LC improves the microenvironment damaged by oxidative stress (induced by hyperglycemia), thus proposing this nutraceutical compound as an adjuvant in diabetic cardiac regenerative medicine.

L-carnitine supplementation attenuates NAFLD progression and cardiac dysfunction in a mouse model fed with methionine and choline-deficient diet

“…Romestaing et al [32] have demonstrated the increase in COX expression mediated by MCDD that alters mitochondrial metabolism, as demonstrated with elevated ROS level. In addition, other studies have described the capacity of LC to attenuate ROS accumulation and cardiac dysfunctions in ischemic or irradiated hearts [44,45] and to decrease oxidative stress in normal and hyperglycemic cardiomyocytes [46,21]. The present study confirmed that LC attenuates ROS production in the liver (Fig.…”

“…Recent studies have suggested the role of oxidative pathways as favourable targets for the treatment of NAFLD [19]. LC has been recognized as a nutritional supplement with anti-oxidative properties [20] and used as an adjunctive therapy in various heart conditions with promising results [21]. In particular, Strilakou et al have described the beneficial effects of LC on a cardiomyopathy rat model fed with a choline-deficient diet [22].…”

l-Carnitine counteracts in vitro fructose-induced hepatic steatosis through targeting oxidative stress markers

“…1a. These doses were chosen based on literature data [18,19]. We studied HepG2 growth capacity to evaluate the absence of cytotoxic effects.…”

“…Our group has recently demonstrated that LC could regulate cellular anti-oxidative responses [18][19][20]26]. Since mitochondria are the primary intracellular regulator of ROS balance, LC effect on mitochondrial activity in HepG2 cells was studied.…”

“…l-Carnitine (LC) plays a critical role in a number of intracellular and metabolic functions, such as fatty acid transport into the mitochondria, stabilization of cell membranes, and reduction of serum lipid levels [17]. Moreover, recent evidence has showed, as LC is also a potent antioxidant: in vitro studies, performing mouse myoblasts [18], rat cardiomyocytes [19] and human osteoblastic cells [20], LC supplementation decrease ROS overproduction and cellular antioxidant defense system.…”