scholarly journals Effect of Fidarestat andα-Lipoic Acid on Diabetes-Induced Epineurial Arteriole Vascular Dysfunction

2004 ◽  
Vol 5 (2) ◽  
pp. 123-135 ◽  
Author(s):  
M. A. Yorek ◽  
L. J. Coppey ◽  
J. S. Gellett ◽  
E. P. Davidson ◽  
D. D. Lund
Keyword(s):  
Body Weight ◽  
Combination Therapy ◽  
Lipoic Acid ◽  
Vascular Dysfunction ◽  
Motor Nerve ◽  
Diabetic Rats ◽  
Motor Nerve Conduction Velocity ◽  
Dihydrolipoic Acid ◽  
Higher Doses ◽  
Neural Dysfunction

In the present study, the authors examined whether treating streptozotocin-induced diabetic rats with the combination ofα-lipoic acid and fidarestat, an aldose reductase inhibitor, can promote the formation of dihydrolipoic acid in diabetic animals and thereby enhance the efficacy ofα-lipoic acid as monotherapy toward preventing diabetic vascular and neural dysfunction.Treating diabetic rats with the combination of 0.25%α-lipoic acid (in the diet) and fidarestat (3 mg/kg body weight) prevented the diabetesinduced slowing of motor nerve conduction velocity and endoneurial blood flow. This therapy also significantly improved acetylcholine-mediated vasodilation in epineurial arterioles of the sciatic nerve compared to nontreated diabetic rats. Treating diabetic rats with 0.25%α-lipoic acid and fidarestat (3 mg/kg body weight) was equally or more effective in preventing vascular and neural dysfunction than was monotherapy of diabetic rats with higher doses ofα-lipoic acid or fidarestat. Treating diabetic rats with the combination of 0.25%α-lipoic acid and fidarestat (3 mg/kg body weight) significantly improved several markers of oxidative stress and increased the serum levels of bothα-lipoic acid and dihydrolipoic acid. These studies suggest that combination therapy consisting ofα-lipoic acid and fidarestat may be more efficacious in preventing diabetes-induced vascular and neural dysfunction in peripheral tissue compared to monotherapy, which requires higher doses to be equally effective. The effect of this combination therapy may in part be due to the increased production and/or level of dihydrolipoic acid.

Progression of vascular and neural dysfunction in sciatic nerves of Zucker diabetic fatty and Zucker rats

2005 ◽  
Vol 289 (1) ◽  
pp. E113-E122 ◽  
Author(s):  
Christine L. Oltman ◽  
Lawrence J. Coppey ◽  
Jill S. Gellett ◽  
Eric P. Davidson ◽  
Donald D. Lund ◽  
...  
Keyword(s):  
Motor Nerve ◽  
Diabetic Rats ◽  
Motor Nerve Conduction Velocity ◽  
Zucker Rats ◽  
Vascular Relaxation ◽  
Calcitonin Gene ◽  
Markers Of Oxidative Stress ◽  
Endoneurial Blood Flow ◽  
Zdf Rats ◽  
Neural Dysfunction

We have examined the progression of vascular and neural deficits in Zucker rats, Zucker diabetic fatty (ZDF) diabetic rats, and age-matched lean ZDF rats from 8 to 40 wk of age. Both the ZDF diabetic and Zucker rats were glucose intolerant at 8 wk of age. The Zucker rats did not become hyperglycemic but were hyperinsulinemic through 32 wk of age. All ZDF diabetic rats became hyperglycemic by 8 wk of age. Through their life span, serum free fatty acids and triglycerides levels were significantly higher in Zucker and ZDF diabetic rats compared with age-matched lean ZDF rats. After 24 and 28 wk of age, endoneurial blood flow was significantly decreased in ZDF diabetic and Zucker rats. Motor nerve conduction velocity was significantly decreased after 12–14 wk of age in ZDF diabetic rats and at 32 wk of age in Zucker rats. ACh-mediated vascular relaxation of epineurial arterioles of the sciatic nerve was impaired after 8–10 wk of age in ZDF diabetic rats and after ∼16 wk of age in Zucker rats. In contrast, vascular relaxation mediated by calcitonin gene-related peptide was impaired significantly after 28 wk of age in ZDF diabetic rats but not impaired in Zucker rats up to 40 wk of age. Markers of oxidative stress were differentially elevated in ZDF diabetic rats and Zucker rats. These data indicate that vascular and neural dysfunction develops in both Zucker and ZDF diabetic rats but at different rates, which may be the result of hyperglycemia.

Effect of treatment of diabetic rats with dehydroepiandrosterone on vascular and neural function

2002 ◽  
Vol 283 (5) ◽  
pp. E1067-E1075 ◽  
Author(s):  
Mark A. Yorek ◽  
Lawrence J. Coppey ◽  
Jill S. Gellett ◽  
Eric P. Davidson ◽  
Xinyu Bing ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Atpase Activity ◽  
Motor Nerve ◽  
Antioxidant Properties ◽  
Diabetic Rats ◽  
Motor Nerve Conduction Velocity ◽  
Neural Function ◽  
Adrenal Androgen ◽  
Dhea Treatment ◽  
Neural Dysfunction

Nutritional supplementation with dehydroepiandrosterone (DHEA) may be a candidate for treating diabetes-induced vascular and neural dysfunction. DHEA is a naturally occurring adrenal androgen that has antioxidant properties and is reportedly reduced in diabetes. Using a prevention protocol, we found that dietary supplementation of streptozotocin-induced diabetic rats with 0.1, 0.25, or 0.5% DHEA caused a concentration-dependent prevention in the development of motor nerve conduction velocity and endoneurial blood flow impairment, which are decreased in diabetes. At 0.25%, DHEA significantly prevented the diabetes-induced increase in serum thiobarbituric acid-reactive substances and sciatic nerve conjugated diene levels. This treatment also reduced the production of superoxide by epineurial arterioles of the sciatic nerve. DHEA treatment (0.25%) significantly improved vascular relaxation mediated by acetylcholine in epineurial vessels of diabetic rats. Sciatic nerve Na+-K+-ATPase activity and myoinositol content was also improved by DHEA treatment, whereas sorbitol and fructose content remained elevated. These studies suggest that DHEA, by preventing oxidative stress and perhaps improving sciatic nerve Na+-K+-ATPase activity, may improve vascular and neural dysfunction in diabetes.

scholarly journals Antihyperglycemic and Antihyperlipidemic of Karala (Momordica charantia) Fruits in Streptozotocin Induced Diabetic Rats

2012 ◽  
Vol 5 (1) ◽  
pp. 29-37 ◽  
Author(s):  
MA Hossain ◽  
M Mostofa ◽  
D Debnath ◽  
AKMR Alam ◽  
Z Yasmin ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Body Weight ◽  
Total Cholesterol ◽  
Aqueous Extract ◽  
Diabetic Rats ◽  
Momordica Charantia ◽  
The Body ◽  
Control Group ◽  
Albino Rats ◽  
Higher Doses

To investigate the antihyperglycemic and antihyperlipidemic effect of Momordica charantia (Karala), the aqueous extract of the Karala fruit was tested on streptozotocin (STZ)-induced diabetic rats. Thirty six albino rats were used in the experiment, 30 diabetic and the remaining six as negative control (T1). Diabetes was induced by administering (injecting) STZ at dose of 55mg/kg body weight. Thirty diabetic animals were randomly divided into five groups such as diabetic control group (T2) without any application of treatment, and groups T3,T4,T5 and T6 were treated with aqueous extract of Karala fruits daily at the doses of 250,    500 and 750mg/kg and glibenclamide (at a dose of 5mg/kg body weight) respectively. The body weight was taken and blood samples were collected from individual animal to determine glucose levels at 15 day interval up to 90 days. In addition, Asparate  Transaminenase(AST), Alanine Transaminenase(ALT), Alkaline Phosphatase(ALP), Total cholesterol (TCh) and Triglyceride (TGA) were determined at day 15 and at the end of the experiment. All three doses of Karala extracts reduced diabetic induced blood sugar and the reduction is comparable with standard glibenclamide (GLM) dose particularly with higher doses Karala extracts (500 and 750mg). Karala also prevented body weight loss due to induced diabetes as did by GLM treatment.. The treatment also resulted in a significant reduction of Asparate Transaminenase(AST), Alanine Transaminenase(ALT), Alkaline Phosphatase(ALP), Total cholesterol (TCh) and Triglyceride (TGA) activities of treated rats when compared to the STZ induced  diabetic rats. Higher doses of Karala (500 and 750mg/kg) are as effective as standard GLM dose on measured variables. This study demonstrated that Karala has hyperglycemia and antihyperlipidemic effect against STZ induced diabetic rats. These findings open the possibility of using Karala extract to treat diabetic animal and human patients although further research is warranted. DOI: http://dx.doi.org/10.3329/jesnr.v5i1.11550 J. Environ. Sci. & Natural Resources, 5(1): 29 - 37, 2012  

Sign in / Sign up

Export Citation Format

Share Document