Acetylcholine-preserving benefits of benfotiamine
Kofi
Mol Cell Biochem. 2009 Jan;320(1-2):149-62. Epub 2008 Oct 2.
Ameliorative effect of combination of benfotiamine and fenofibrate in
diabetes-induced vascular endothelial dysfunction and nephropathy in the
rat.
Balakumar P, Chakkarwar VA, Singh M.
Cardiovascular Pharmacology Division, ISF College of Pharmacy, Moga, 142
001, India,.
The study has been designed to investigate the effect of benfotiamine
and fenofibrate in diabetes-induced experimental vascular endothelial
dysfunction (VED) and nephropathy. The single administration of
streptozotocin (STZ) (50 mg/kg, i.p.) produced diabetes, which was noted
to develop VED and nephropathy in 8 weeks. The diabetes produced VED by
attenuating acetylcholine-induced endothelium dependent relaxation,
impairing the integrity of vascular endothelium, decreasing serum
nitrite/nitrate concentration and increasing serum TBARS and aortic
superoxide anion generation. Further, diabetes altered the lipid profile
by increasing the serum cholesterol, triglycerides and decreasing the
high density lipoprotein. The nephropathy was noted to be developed in
the diabetic rat that was assessed in terms of increase in serum
creatinine, blood urea, proteinuria, and glomerular damage. The
benfotiamine (70 mg/kg, p.o.) and fenofibrate (32 mg/kg, p.o.) or
lisinopril (1 mg/kg, p.o., a standard agent) treatments were started in
diabetic rats after 1 week of STZ administration and continued for 7
weeks. The treatment with benfotiamine and fenofibrate either alone or
in combination attenuated diabetes-induced VED and nephropathy. In
addition, the combination of benfotiamine and fenofibrate was noted to
be more effective in attenuating the diabetes-induced VED and
nephropathy when compared to treatment with either drug alone or
lisinopril. Treatment with fenofibrate normalizes the altered lipid
profile in diabetic rats, whereas benfotiamine treatment has no effect
on lipid alteration in diabetic rats. It may be concluded that
diabetes-induced oxidative stress, lipids alteration, and consequent
development of VED may be responsible for the induction of nephropathy
in diabetic rats. Concurrent administration of benfotiamine and
fenofibrate may provide synergistic benefits in preventing the
development of diabetes-induced nephropathy by reducing the oxidative
stress and lipid alteration, preventing the VED and subsequently
improving the renal function.
PMID: 18830571
Pharmacol Res. 2008 Nov-Dec;58(5-6):356-63. Epub 2008 Oct 2.
Benfotiamine attenuates nicotine and uric acid-induced vascular
endothelial dysfunction in the rat.
Balakumar P, Sharma R, Singh M.
Cardiovascular Pharmacology Division, ISF College of Pharmacy, Moga
142001, Punjab, India
The study has been designed to investigate the effect of benfotiamine, a
thiamine derivative, in nicotine and uric acid-induced vascular
endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1),
i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were
administered to produce VED in rats. The development of VED was assessed
by employing isolated aortic ring preparation and estimating serum and
aortic concentration of nitrite/nitrate. Further, the integrity of
vascular endothelium was assessed using the scanning electron microscopy
(SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by
estimating serum thiobarbituric acid reactive substances (TBARS) and
aortic superoxide anion generation. The administration of nicotine and
uric acid produced VED by impairing the integrity of vascular
endothelium and subsequently decreasing serum and aortic concentration
of nitrite/nitrate and attenuating acetylcholine-induced endothelium
dependent relaxation. Further, nicotine and uric acid produced oxidative
stress, which was assessed in terms of increase in serum TBARS and
aortic superoxide generation. However, treatment with benfotiamine (70
mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a
standard agent) markedly prevented nicotine and uric acid-induced VED
and oxidative stress by improving the integrity of vascular endothelium,
increasing the concentration of serum and aortic nitrite/nitrate,
enhancing the acetylcholine-induced endothelium dependent relaxation and
decreasing serum TBARS and aortic superoxide anion generation. Thus, it
may be concluded that benfotiamine reduces the oxidative stress and
consequently improves the integrity of vascular endothelium and enhances
the generation of nitric oxide to prevent nicotine and uric acid-induced
experimental VED.
Publication Types:
* In Vitro
PMID: 18951979