Effect of rosiglitazone in sodium arsenite-induced experimental vascular endothelial dysfunction.
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.
Kaur
Tajpreet
T
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002, India.
Goel
Rajesh Kumar
RK
Balakumar
Pitchai
P
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018053:Arsenites / Q000633:toxicity*; D001786:Blood Glucose / Q000032:analysis; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077154:Rosiglitazone; D017670:Sodium Compounds / Q000633:toxicity*; D045162:Thiazolidinediones / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D018053:Arsenites; D001786:Blood Glucose; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D017670:Sodium Compounds; D045162:Thiazolidinediones; D017392:Thiobarbituric Acid Reactive Substances; D014874:Water Pollutants, Chemical; D000077154:Rosiglitazone; D009569:Nitric Oxide; C017947:sodium arsenite; D005978:Glutathione