Toxic effect of high glucose on cardiomyocytes, H9c2 cells: Induction of oxidative stress and ameliorative effect of trolox

Abstract

Oxidative stress (OS) has been implicated in a variety of pathological conditions, including diabetes mellitus, characterized by hyperglycemia. In the present study, OS induced by hyperglycemia and the effect of trolox, a vitamin E analog, were studied in cardiomyocytes and H9c2 cells exposed to 15 to 33 mM glucose (HG) for 24 to 72 hours in Dulbecco modified Eagle medium. Cells treated wirh 24 or 33 mM glucose for 24 hours or above showed decreased viability and adenosine triphosphate (ATP) content with a concomitant increase in radicals of oxygen species, calcium (Ca2+), mitochondrial permeability transition, and oxidative markers, confirming that the cells were under stress. However, upon exposure to 15 mM glucose for 24 hours, H9c2 cells maintained homeostasis and ATP generation. Pretreatment of cells with trolox reduced HG‐induced OS to control levels. Here, we report that the toxic effect of HG is highly regulated and that OS induction can be prevented with Trolox, a potential inhibitor of membrane damage.

An In Vitro Study on the Combination Effect of Metformin and N-Acetyl Cysteine against Hyperglycaemia-Induced Cardiac Damage

“…The following day, to assess the ability of NAC plus MET to attenuate high glucose-induced cardiac injury, H9c2 cardiomyoblasts were treated with either 1 mM NAC, 1 µM MET or a combination of NAC plus MET for 24 h. Cells exposed to either normal glucose (NG; 5.5 mM) or HG were treated with the vehicle control. All treatment doses were based on results obtained from previous studies [4,7,[18][19][20][21].…”

“…This rising diabetes epidemic contributes significantly to the aetiology of cardiovascular dysfunction, with diabetic individuals presenting increasingly with heart failure (HF) [2]. A large body of evidence suggests that chronic hyperglycaemia, linked to augmented reactive oxygen species (ROS) levels and oxidative stress, plays a major role in the development and progression of deteriorated cardiac function [3][4][5][6]. For example, in the diabetic heart, aberrant glucose auto-oxidation and shifts in redox balance are known to decrease tissue concentration of glutathione (GSH) and impair antioxidant defence enzymes, such as superoxide dismutase (SOD) and catalase (CAT) [5,7].…”

Trolox prevents high glucose‐induced apoptosis in rat myocardial H9c2 cells by regulating GLUT‐4 and antioxidant defense mechanism

“…OS is a major mechanism for hyperglycemia‐mediated injury in both in‐vivo and in‐vitro conditions . Earlier studies from our laboratory have led to the conclusion that increased ROS and intracellular calcium (Ca 2+ ) i are primarily responsible for high glucose‐induced cardiac cell toxicity . The present study addresses both aspects of failing glucose transport and antioxidant status in cardiac cells and Trolox's protective attributes in high‐glucose‐mediated OS and cell death in H9c2 cells.…”

“…Due to changes in ΔΨm, mitochondria appear to release apoptosis‐inducing factors that cause DNA fragmentation . Earlier, we reported that mitochondrial dysfunction involving MPT changes and declines in ATP has been demonstrated recently in H9c2 cells during exposure to high glucose . The cell's process toward apoptosis is irreversible after the collapse of ΔΨm .…”

“…OS, as well as the elevation of (Ca 2+ )i and ROS, have been implicated for high‐glucose‐mediated cardiac cell death . Apoptosis and subsequent cardiac dysfunction is the key feature of diabetic cardiomyopathy .…”