Background
Hydrogen sulfide (H&sub2;S) has been shown to have cytoprotective effects in models of hypertension, ischemia/reperfusion and Alzheimer's disease. However, little is known about its effects or mechanisms of action in atherosclerosis. Therefore, in the current study we evaluated the pharmacological effects of H&sub2;S on antioxidant defenses and mitochondria protection against hydrogen peroxide (H&sub2;O&sub2;) induced endothelial cells damage. Methodology and principal findings: H&sub2;S, at non-cytotoxic levels, exerts a concentration dependent protective effect in human umbilical vein endothelial cells (HUVECs) exposed to H&sub2;O&sub2;. Analysis of ATP synthesis, mitochondrial membrane potential (ΔΨm) and cytochrome c release from mitochondria indicated that mitochondrial function was preserved by pretreatment with H&sub2;S. In contrast, in H&sub2;O&sub2; exposed endothelial cells mitochondria appeared swollen or ruptured. In additional experiments, H&sub2;S was also found to preserve the activities and protein expressions levels of the antioxidants enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in H&sub2;O&sub2; exposed cells. ROS and lipid peroxidation, as assessed by measuring H&sub2;DCFDA, dihydroethidium (DHE), diphenyl-l-pyrenylphosphine (DPPP) and malonaldehyde (MDA) levels, were also inhibited by H&sub2;S treatment. Interestingly, in the current model, D, L-propargylglycine (PAG), a selective inhibitor of cystathionine γ-lyase (CSE), abolished the protective effects of H&sub2;S donors. Innovation: This study is the first to show that H&sub2;S can inhibit H&sub2;O&sub2; mediated mitochondrial dysfunction in human endothelial cells by preserving antioxidant defences. Significance: H&sub2;S may protect against atherosclerosis by preventing H&sub2;O&sub2; induced injury to endothelial cells. These effects appear to be mediated via the preservation of mitochondrial function and by reducing the deleterious effects of oxidative stress.
Significance
H&sub2;S may protect against atherosclerosis by preventing H&sub2;O&sub2; induced injury to endothelial cells. These effects appear to be mediated via the preservation of mitochondrial function and by reducing the deleterious effects of oxidative stress.