title: The defensive effect of benfotiamine in sodium arsenite-induced experimental vascular endothelial dysfunction.
abstract: The present study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Sodium arsenite (1.5 mg(-1) kg(-1) day(-1) i.p., 2 weeks) was administered in rats to produce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating the serum and aortic concentrations of nitrite/nitrate. Further, the integrity of vascular endothelium in thoracic aorta was assessed by scanning electron microscopy. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of sodium arsenite markedly produced VED by attenuating acetylcholine-induced endothelium-dependent relaxation, decreasing serum and aortic concentrations of nitrite/nitrate, and impairing the integrity of vascular endothelium. Further, sodium arsenite produced oxidative stress by increasing serum TBARS and aortic superoxide generation. The treatment with benfotiamine (25, 50, and 100 mg(-1) kg(-1) day(-1) p.o.) or atorvastatin (30 mg(-1) kg(-1) day(-1) p.o., a standard agent) prevented sodium arsenite-induced VED and oxidative stress. However, the beneficial effects of benfotiamine in preventing the sodium arsenite-induced VED were attenuated by co-administration with N-omega-nitro-L: -arginine methyl ester (L: -NAME) (25 mg(-1) kg(-1) day(-1), i.p.), an inhibitor of NOS. Thus, it may be concluded that benfotiamine reduces oxidative stress and activates endothelial nitric oxide synthase to enhance the generation and bioavailability of NO and subsequently improves the integrity of vascular endothelium to prevent sodium arsenite-induced experimental VED.
authors: Cardiovascular Pharmacology Division, ISF College of Pharmacy, Moga, 142 001, Punjab, India.
authors: Sanjali
authors: S
authors: Verma
authors: Krishna
authors: K
authors: Reddy
authors: Pitchai
authors: P
authors: Balakumar
mesh_terms: D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000633:toxicity*; D008855:Microscopy, Electron, Scanning; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017670:Sodium Compounds / Q000633:toxicity*; D013831:Thiamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D018053:Arsenites; D004791:Enzyme Inhibitors; D017670:Sodium Compounds; D017392:Thiobarbituric Acid Reactive Substances; C017947:sodium arsenite; D052250:Nitric Oxide Synthase Type III; D013831:Thiamine; C013835:benphothiamine