Effect of rosiglitazone in sodium arsenite-induced experimental vascular endothelial dysfunction

Abstract

The present study has been designed to investigate the effect of rosiglitazone, a peroxisome proliferator activated receptor gamma agonist in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. The rats were administered sodium arsenite (1.5 mg/kg/day, i.p., 2 weeks) to induce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum nitrite/nitrate concentration. Further, the integrity of the aortic endothelium was assessed histologically using haematoxylin-eosin staining. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances, aortic reactive oxygen species and reduced form of glutathione. The administration of sodium arsenite produced VED by impairing acetylcholine-induced endothelium dependent relaxation, diminishing the integrity of vascular endothelium and decreasing the serum nitrite/nitrate concentration. In addition, sodium arsenite was noted to produce oxidative stress as it increased serum thiobarbituric acid reactive substances and aortic reactive oxygen species and consequently decreased glutathione. Treatment with rosiglitazone (3 mg/kg/day, p.o., 2 weeks and 5 mg/kg/day, p.o., 2 weeks) significantly prevented sodium arsenite-induced VED by enhancing acetylcholine-induced endothelium dependent relaxation, improving the integrity of vascular endothelium, increasing the nitrite/nitrate concentration and decreasing the oxidative stress. However, the vascular protective effect of rosiglitazone was markedly abolished by co-administration of nitric oxide synthase inhibitor, N-Omega-Nitro-L-Arginine Methyl Ester (L-NAME) (25 mg/kg/day, i.p., 2 weeks). Thus, it may be concluded that rosiglitazone reduces oxidative stress, activates eNOS and enhances the generation of nitric oxide to prevent sodium arsenite-induced VED in rats.

Coenzyme Q10 suppresses oxLDL‐induced endothelial oxidative injuries by the modulation of LOX‐1‐mediated ROS generation via the AMPK/PKC/NADPH oxidase signaling pathway

“…Clinical parameters confirmed that rosiglitazone reduces LDL, increase HDL as well as reduces triglycerides in human plasma 67. Besides, previous study reported rosiglitazone protect against sodium arsenite‐induced vascular endothelial dysfunction and intracellular ROS generation, indicating that rosiglitazone acts the role of anti‐oxidant 68. In addition, metformin, an AMPK activators also, was reported have positive effects of endothelial parameters in DM patients 69, 70.…”

The PPARγ Agonist Protects Cardiomyocytes from Oxidative Stress and ApoptosisviaThioredoxin Overexpression

“…Besides glucose control, RSG shows diverse therapeutic effects in the regulation of endothelial function, cellular apoptosis, tissue fibrosis, and the control of blood pressure. [28][29][30][31][32] In addition, it limits cardiac hypertrophy in diet-induced hypercholesterolemic rats by the renin-angiotensin system. 16) Furthermore, current evidence suggests that it has beneficial effects on CMCs under oxidative stress.…”

Mechanisms pertaining to arsenic toxicity

“…Recently, a couple of studies from our laboratory demonstrated that treatment with either bis-(maltolato) oxovanadium, an inhibitor of protein tyrosine phosphatase, or rosiglitazone, an agonist of peroxisome proliferator activated receptor-gamma (PPAR-γ) markedly ameliorated sodium arsenite-induced vascular endothelial dysfunction in rats by enhancing the integrity of vascular endothelium, improving endothelium-dependent relaxation and reducing oxidative stress. [3334]…”