EFFECTS OF SIMVASTATIN AND ALPHA-TOCOPHEROL ON DISTURBED NERVE CONDUCTION IN OBESE SPRAGUE DAWLEY RATS

Asma Jabeen, Umar Ali Khan, Muhammad Ayub, M. Amjad Hameed

Abstract


Background: The incidence of obesity is increasing worldwide. The neuropathy associated with
obesity, that is evident from disturbed nerve conduction, is one of the complications for which a
number of treatment options are being considered. In this study, Simvastatin, a hydroxyl methyl
glutaryl coenzyme A reductase inhibitor and alpha-tocopherol, a dietary antioxidant are compared
for their effects on sciatic nerve conduction velocity. Objectives: To compare the effects of
Simvastatin and alpha-tocopherol on sciatic nerve conduction velocity in obese rats. Methods:
The study was a Randomised control trial conducted from December 2008 to November 2009.
One hundred and twenty adult male Sprague Dawley rats were divided into four groups with 30
rats in each group. One group of rats was taken as control with normal diet while other three
groups were given high fat diet (HFD) for the whole study period. Along with the high fat diet,
group III and group IV were given Simvastatin and alpha-tocopherol supplemented diet
respectively. At the end of study, conduction velocity of sciatic nerve was determined with the
help of PowerLab® data acquisition system. Results: The three groups with HFD showed more
than 25% increase in weight at the end of study compared to control group. The control group
with high fat diet (Group II) showed decreased sciatic nerve conduction velocity when compared
with control (Group I). Both the groups that were given Simvastatin and alpha-tocopherol each
showed improvement in sciatic nerve conduction velocity (p<0.001) after four weeks when
compared with the group that was given HFD without any supplementation. However with alphatocopherol, the nerve conduction velocity was improved more significantly. Conclusions:
Simvastatin and alpha-tocopherol both are effective for improving sciatic nerve conduction
velocity in HFD induced obesity.
Keywords: Obesity, Simvastatin, nerve conduction velocity, alpha-tocopherol, High Fat Diet

Full Text:

PDF

References


Eckersley ME, Losing the battle of the bulge: causes and

consequences of increasing obesity. Med J Aust 2001;174:590–

Shafi S, Rao MH, Soomro IB. The effect of life style and socioeconomic factors in the development of obesity in young adults.

Pak J Med Res 2004;43(2):65–9.

Knobler H, Malnick SDH. The medical complications of obesity.

Q J Med 2006;99:565–79.

Nishikawa S, Yasoshima A, Doi K, Nakayama H, Uetsuka K.

Involvement of sex, strain and age factors in high fat diet induced

obesity in C-57BL/6J and BALB/cA mice. Exp Anim

;56:263–72.

Ylitalo KR, Sowers M, Heeringa S. Peripheral neuropathy in

individuals with cardiometabolic clustering and obesity. Diabetes

Care 2011;34:1642–7.

Miscio G, Guastamacchia G, Brunani A, Priano L, Baudo S,

Mauro A. Obesity and peripheral neuropathy risk: a dangerous

liaison. J Peripher Nerv Syst 2005;10:354–8.

Hilton TN, Tuttle LJ, Bohnert KL. Mueller MJ, Sinacore DR.

Excessive adipose tissue infiltration in skeletal muscle in

individuals with obesity, diabetes mellitus and peripheral

neuropathy: Association with performance and function. Phys

Ther 2008;88:1336–44.

Ziegler D, Sohr CGH, Nourooz-Zadeh J. Oxidative stress and

antioxidant defense in relation to the severity of diabetic

polyneuropathy and cardiovascular autonomic neuropathy.

Diabetic Care 2004;27:2178–83.

Low AP, Nickander KK, Tritschler HJ. The roles of oxidative

stress and antioxidant treatment in experimental diabetic

neuropathy. Diabetes 1997;46:38–42.

Stahl W, Sies H. Antioxidant defence: vitamin E and C and

carotenoids. Diabetes 1997;46:14–8.

Pace A, Giannarelli D, Galie E, Savarese A, Carano S, Della

GM, et al. Vitamin E neuroprotection for cisplatin neuropathy: a

randomized, placebo controlled trial. Neurology 2010;74:762–6.

Cameron NE. Metabolic and vascular factors in the pathogenesis

of diabetec neuropathy. Diabetes 1997;46:31–7.

Obrosova IG, Inytska O, Lysogubov VV, Pavlov IA, Mashtalir

N, Nadler JL, et al. High fat diet induced neuropathy of prediabetes and obesity. Effects of “healthy” diet and aldose

reductase inhibition. Diabetes 2007;56:2598–608.

Sparrow CP, Burton CA, Hernandez M, Mundt S, Hassing H,

Patel S, et al. Simvastatin has anti-inflammatory and

antiatherosclerotic activities independent of plasma cholesterol

lowering. Arterioscler Thromb Vasc Biol 2001;21:115–21.

Oltman CL, Coppey LJ, Gellett JS, Davidson EP, Lund DD,

Yorek MA. Progression of vascular and neural dysfunction in

sciatic nerves of Zucker diabetic fatty and Zucker rats. Am J

Physiol Endocrinal Metab 2005;289:113–22.

Tawfik HE, El-Remessy AB, Matragoon S, Ma G, Caldwell RB,

Caldwell RW. Simvastatin improves diabetes induced coronary

endothelial dysfunction. J Pharmacol Exp Tther 2006;319:386–

Levin BE, Dunn-Meynell AA. Defense of body weight depends

on dietary composition and palatability in rats with diet induced

obesity. Am J Physiol Regulatory Integrative Comp Physiol

;282:46–54.

Head KA. Peripheral neuropathy: Pathogenic mechanisms and

alternative therapies. Alternative Medicine Review

;11(4):294–329.

Coppey LJ, Gellett JS, Davidson EP, Dunlap JA, Lund DD,

Yorek MA. Effect of antioxidant treatment of streptozotocininduced diabetic rats on endoneurial blood flow, motor nerve

conduction velocity and vascular reactivity of epineurial

arterioles of the sciatic nerves. Diabetes 2001;50:1927–37.

Delbosc S, Cristol JP, Descomps B, Mimran A , Jover B.

Simvastatin prevents angiotensin II induced cardiac alterations

and oxidative stress. Hypertension 2002;40:142–7.

Tutunco NB, Bayraktar M, Varli K. Reversal of defective nerve

conduction with vitamin E supplementation in type 2 diabetes.

Diabetec Care 1998;21:1915–8.

Klivenyi P, Karg E, Rozsa C, Horvath R, Komoly S, Nemeth I, et

al. Alpha-tocopherol/ lipid ratio in blood is decreased in patients

with Leber’s hereditary optic neuropathy and asymptomatic

carriers of the 1178 mtDNA mutation. J Neurol Neurosurg

Psychiatry 2001;70:359–62.

Khanna S, Roy S, Parinandi NL, Maurer M, Sen CK.

Characterization of the potent neuroprotective properties of the

natural vitamin E á-tocotrienol. J Neurochem 2006;98:1474–86.

Van Dam PS, Brvenboer B, Van Asbeck BS, Marx JJ, Gispen

WH. High rat food vitamin E content improves nerve function in

streptozotocin-diabetic rats. Eur J Pharmacol 1999;376:217–22.


Refbacks

  • There are currently no refbacks.


Contact Number: +92-992-382571

email: [jamc] [@] [ayubmed.edu.pk]