RESEARCH ARTICLE e-ISSN: 2454-7867
Prasanna Kumar B et al. Int J Trends in Pharm & Life Sci. 2015: 1(5);600-612 . 600
Available online at www.ijtpls.com
International Journal of Trends in Pharmacy and Life Sciences Vol. 1, Issue: 5, 2015: 600-612
EFFECT OF VITAMIN E ON ATORVASTATIN INDUCED SELECTED
BEHAVIORAL AND BIOCHEMICAL ALTERATIONS IN NORMAL RATS B. Prasanna Kumar, K. Sravanth & D. Rama brahma Reddy
Nalanda institute of Pharmaceutical Sciences, Siddharth Nagar, Kantepudi(Village),
Sattenapalli(Mandal), Guntur(Dist)-522438 E.Mail: [email protected]
ABSTRACT
Atorvastatin is synthetic compound containing a heptanoic acid side chain that forms a structural
analog of the HMG-CoA intermediate. Atorvastatin, like all statins, is a selective, competitive inhibitor of
HMG-CoA reductase. The aim of the Study is to find out the Possible Role of Vitamin E on Atorvastatin
Induced Behavioural and Selected biochemical alterations in Normal Rats. The results of the present study
showed that, chronic treatment with Atorvastatin produce Neuro pharmacological and Biochemical
alterations such as decreased body weight, exploratory behaviour, loco motor activity, motor co –
ordination, muscle grip strength and depression . Decrease in levels of antioxidant enzymes. Vitamin E
Supplementation decreased Atorvastatin induced Neuro pharmacological and severe side effects the
increasing anti-oxidant enzymes SOD, CAT, gultathion, Dose dependently.
*Corresponding Author:
Mr.B. Prasanna Kumar,
Nalanda institute of Pharmaceutical Sciences, Siddharth Nagar,
Kantepudi(Village),
Sattenapalli(Mandal), Guntur(Dist)-522438 E.Mail: [email protected]
INTRODUCTION
Over the past decade, there has been substantial interest in oxidative stress and its potential role in
epilepsy, development of diabetic complications, atherosclerosis and associated cardiovascular disease.
Consequences of oxidative stress are damage to DNA, lipids, proteins, resulting in the disruption of cellular
homeostasis. 3-hydroxy-3-methyl glutaryl co-enzyme A (HMG – CoA reductase) inhibitors are the most
widely prescribed drugs in the world and the United States and contributed substantially to prescription drug
cost increases in 2001. [1].Atorvastatin in most widely prescribed statin drug. It is drug of choice for
treatment of elevated cholesterol and congestive heart diseases and obesity .Cholesterol is a vital substance
of the body, at the lower levels of cholesterol mortality is increased due to non-cardiovascular deaths, like
cancer, accidents and depression [2].
Atorvastatin is synthetic compound containing a heptanoic acid side chain that forms a structural
analog of the HMG-CoA intermediate. Atorvastatin, like all statins, is a selective, competitive inhibitor of
HMG-CoA reductase.
Vitamin E is the principle membrane-associated antioxidant molecule in mammals. It plays a major
role in preventing oxidative damage to membrane lipids by scavenging free radicals. [3,4].
Received: 22/10/2015
Revised: 20/11/2015
Accepted: 28/11/2015
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The aim of the Study is to find out the Possible Role of Vitamin E on Atorvastatin Induced Behavioural
and Selected biochemical alterations in Normal Rats.
MATERIALS AND METHODS
Experimental Animals
Pathogen free adult male albino rats weighing 150-200 g were used. Male rats were chosen to avoid
fluctuations due to oestrous cycle (Sugioka et al., 1987). The rats were housed in polypropylene cages (Five
per cage) under standard laboratory conditions with 12 hours light / dark cycle. The rats were fed with
standard laboratory chow (NATIONAL INSTITUTE OF NUTRITION) and Water ad libitum.
Study Protocol
Grouping of Animals
The animals were divided in to six groups of 5 each
1. Group-I : Normal control
2. Group-II : Vitamine E group
3. Group-III : Atorvastatin group (10 mg/kg)
4. Group-IV : Atorvastatin + Low dose of vitamin E 50 mg/kg
5. Group-V : Atorvastatin + Middle dose of vitamin E 100 mg/kg
6. Group-VI : Atorvastatin + highest dose of vitamin E 200 mg/kg
Drugs and treatment schedule
Atorvastatin at a dose of 10 mg/kg diluted with 0.2% CMC was administered by oral gauge daily
between 8.00 to 9.00 am for 4-6 weeks [5, 6, 7,8]
Vitamin E, a lipid soluble antioxidant, at doses of 50, 100, 200 mg/kg was suspended in 1% of tween
80 and was administered orally once (one hour before Atorvastatin) treatment Control group
received 1% solution of tween 80 orally daily for 4-6 weeks.
Behavioural Parameters: On every 15 day, 24 hours after drug treatment all behavioural parameters were
studied. All animals were handled for at least for 7 days before testing behavioural parameters.
Motor Co-ordination test: Motor co-ordination test was conducted in groups of rats using a Rota rod
Apparatus (Inco Ambala). The animals were placed on the Moing rod prior to the treatment and the rats that
stayed on the rod without falling for 120 sec chosen for the study [9]
Exploratory Behaviour test: This test was done using Hole Board. The hole Board consisted of a 0.5 m3
wooden board with 16 holes (3 cm in diameter). Each rat was placed singly on the board for a period of 6
minutes. The number of exploratory movements performed within the last 4 minutes of this period was
noted for each animal [10]
Locomotor Activity: The locomotor activity can be easily measured using an Actophotometer which
operates on photo electric cells which are connected in circuit with a counter. When the beam of light
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falling on photo cell is cut off by the animal, a count is recorded. An Actophotometer could have either
circular (or) square area in which the animal moves. Both rats and mice may be used for testing in this
equipment.
Body Weight Analysis: On the first day of the experiment each animal weight noted and expressed in
grams. Weight analysis is done for 15 days up to 45 days.
Biochemical Analyses: Blood samples were collected at the end of the experiment from retro-orbital plexus
under light ether anesthesia. Blood samples were kept for 30-60 minutes in dry test tubes without any
disturbance, citrated blood is used for obtaining plasma. Then centrifuged for 10 minutes at 3000 rpm to
separate the serum and plasma.
Blood was analyzed for aspartate transminase (AST) [11].
On 45th
day blood samples were collected from retro-orbital plexus and estimated for
superoxide dismutase, catalase [12] glutathione [13]
Statistical Analysis
All the values are expressed as mean ± SD. The statistical analysis was carried out using Two way
analysis of variance (ANOVA) followed by Tukey’s mutiple comparison test. In all tests, the criterion for
statistical significance was p< 0.05, p<0.01, p<0.001 were considered as significant.
RESULTS AND DISCUSSION
Body Weight: -Chronic Atorvastatin 10mg/kg treatment significantly decreased (p<0.01) the body weight
in all treatment groups except vitamin E treated group on 15th
day when compared to the control group (fig.
1). Vitamin E 50 mg/kg treatment did not increase the Atorvastatin decreased body weight when compared
to Atorvastatin treatment group. Vitamin E 100 and 200mg/kg treatment significantly increase (P<0.05 and
P.01) the Atorvastatin decreased body weight on 30th
day when compared to the Atorvastatin treatment
group (fig . 1). And maintained the body weight when compared to the control group (fig 1 ).
Table 1: Effect of chronic treatment of Atorvastatin, vitamin E and Atorvastatin + Vitamin E on body
weight
Group
No.
Treatment mg/kg Body weight (days)
0 15 30 45
1. Control 176 ± 25.61 182.4±26.34 188.3 ± 28.310 194 ± 29.81
2. Atorvastatin (10 mg/kg) 180 ± 31.62 176.2 ± 34.89 164.4 ± 31.958 152.2 ± 31.26 b
3. Vitamin E (100 mg/kg) 172.8 ±
32.05
178.6 ± 30.163 182.8± 29.819 189.8 ± 30.27 1a
4. Atorvastatin (10 mg/kg) +
vitamin E
(50 mg/kg)
182.6 ±
27.83
175.8 ± 26.3 186 ± 26.623 1a
196.4 ± 27.53 1a
5. Atorvastatin (10 mg/kg) +
vitamin E
(100 mg/kg)
175.8 ± 26.3 197.2 ± 23.511a, a
199.4 ± 23.44 1b
205 ± 23.17 a 1b
6. Atorvastatin (10 mg/kg) +
vitamin E
(200 mg/kg)
171 ± 24.
597
176.4 ± 22.963 182.4 ± 23.201 187.8 ± 23.541 1a
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Fig.1: Effect of chronic treatment of Atorvastatin, vitamin E and Atorvastatin + Vitamin E on body weight
Note: Values expressed as mean ± SD (N=5)
a, p<0.05; b p<0.01; c p<0.001 vs control group
1a, p<0.05; 1b p<0.01; 1c p<0.001 vs atorvastatin group
2a, p<0.05; 2b p<0.01; 2c p<0.001 vs vitamin E group
3a, p<0.05; 3b p<0.01; 3c p<0.001 vs ator + vitamin E (50 mg/kg)
4a, p<0.05; 4b p<0.01; 4c p<0.001 vs ator + vitamin E (100 mg/kg)
5a, p<0.05; 5b p<0.01; 5c p<0.001 vs ator + vitamin E (200 mg/kg)
(2 WAY ANOVA) followed by TUKEY-KRAMER multiple comparison test
Hole board test: Chronic Atorvastatin at a dose of 10mg/kg significantly decreased (P<0.001) the number
of exploratory movements in all treatment groups except Vitamin E on 30th
day onwards when compared to
the control group (fig-2).
Vitamin E 50mg/kg treatment did not increase the Atorvastatin decreased exploratory movements when
compared to Atorvastatin treatment group. Whereas Vitamin E 100 and 200-mg/kg treatment significantly
increased (P<0.01) and (P<0.001) Atorvastatin decreased exploratory movements on 40th
day and 30th
day
respectively when compared to the Atorvastatin treatment group (fig-2).
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Table 2: Effect of chronic treatment of Atorvastatin, vitamin E and Atorvastatin + Vitamin E on Hole
Board
Group
No.
Treatment mg/kg Hole Board
0 15 30 45
1. Control 16.4 ± 6.542 17.2 ± 3.136 18.6 ± 2.178 20.06 ± 3.876
2. Atorvastatin (10 mg/kg) 16.4 ± 6.542 8.6 ± 2.408 6.8 ± 2.168 5.2 ± 1.924
3. Vitamin E (100 mg/kg) 20.8 ± 4.817 14.6 ± 2.408 15.8 ± 2.28 1b
18.2 ± 2.387 1c
4. Atorvastatin (10 mg/kg) +
vitamin E
(50 mg/kg)
17.8 ± 3.271 15.4 ± 2.881 11.6 ± 5.55 1a
12.8 ± 3.421 1b
5. Atorvastatin (10 mg/kg) +
vitamin E
(100 mg/kg)
22.2 ± 4.919 13.4 ± 3.578 15.6 ± 3.209 1b
20.6 ± 3.975 1c
6. Atorvastatin (10 mg/kg) +
vitamin E
(200 mg/kg)
24 ± 3.536 14.2 ± 2.864 17.6 ± 4.037 1c
21 ± 3.536 1c,3a
Fig.2: Effect of chronic treatment of Atorvastatin, vitamin E and Atorvastatin + Vitamin E on Hole Board
Note: Values expressed as mean ± SD (N=5)
a, p<0.05; b p<0.01; c p<0.001 vs control group
1a, p<0.05; 1b p<0.01; 1c p<0.001 vs atorvastatin group
2a, p<0.05; 2b p<0.01; 2c p<0.001 vs vitamin E group
3a, p<0.05; 3b p<0.01; 3c p<0.001 vs ator + vitamin E (50 mg/kg)
4a, p<0.05; 4b p<0.01; 4c p<0.001 vs ator + vitamin E (100 mg/kg)
5a, p<0.05; 5b p<0.01; 5c p<0.001 vs ator + vitamin E (200 mg/kg)
(2 WAY ANOVA) followed by TUKEY-KRAMER multiple comparison test
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Loco motor activity:
Chronic Atorvastatin 10 mg/kg treatment significantly decreased (P<0.001). The Locomotion in all
treatment groups Except Vitamin E treated group on 30th day when compared to the control group (fig-3).
Vitamin E 50mg/kg treatment did not increase the Atorvastatin decreased Locomotion when compared to
the Atorvastatin treatment group. Vitamin E 100 and 200mg/kg treatment , significantly increased
(P<0.01) the Atorvastatin decreased Locomotion on 45th
day and 30th
day of treatment respectively when
compared to the Atorvastatin treatment group (fig -3).
Table 3: Effect of chronic treatment of Atorvastatin, vitamin E and Atorvastatin + Vitamin E on
Spontaneous motor activity
Group
No.
Treatment mg/kg SMA Count
0 15 30 45
1. Control 167.2 ± 23.25 2a
184 ± 40.97 184 ± 36.73 176 ± 29.31
2. Atorvastatin (10 mg/kg) 144.8 ± 28.38 2a
130.1 ± 36.28 a 112 ± 41.34
a 96.2 ± 11.47
c
3. Vitamin E (100 mg/kg) 181.8 ± 29.21 b 192.8 ± 34.65
1b
187.2 ± 24.26 208.2 ± 23.79 1a
4. Atorvastatin (10 mg/kg)
+ vitamin E
(50 mg/kg)
158.4 ± 19.922b
197.8 ± 27.62 b 139.8 ± 48.42
b, 1a, 2a
122.2 ± 34 b,2a
5. Atorvastatin (10 mg/kg)
+ vitamin E
(100 mg/kg)
170.2 ± 34.10 2b
172.6 ± 57.47 1a
175.6 ± 58.19 a 215 ± 36.1
3b
6. Atorvastatin (10 mg/kg)
+ vitamin E
(200 mg/kg)
172.0 ± 31.23 a 174.0 ± 38.70
b, 1b, 2a
186.8 ± 32.19 a,
2a
187.2 ± 34. a, 4a, 2a
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Fig.3: Effect of chronic treatment of Atorvastatin, vitamin E and Atorvastatin + Vitamin E on Spontaneous
motor activity (SMA)
Note: Values expressed as mean ± SD (N=5)
a, p<0.05; b p<0.01; c p<0.001 vs control group
1a, p<0.05; 1b p<0.01; 1c p<0.001 vs atorvastatin group
2a, p<0.05; 2b p<0.01; 2c p<0.001 vs vitamin E group
3a, p<0.05; 3b p<0.01; 3c p<0.001 vs ator + vitamin E (50 mg/kg)
4a, p<0.05; 4b p<0.01; 4c p<0.001 vs ator + vitamin E (100 mg/kg)
5a, p<0.05; 5b p<0.01; 5c p<0.001 vs ator + vitamin E (200 mg/kg)
(2 WAY ANOVA) followed by TUKEY-KRAMER multiple comparison test
MOTOR CO- ORDINATION TEST:- Chronic Atorvastatin 10mg/kg treatment significantly impaired
(P<0.001) the Rota rod performance from 15th
day of the treatment in all treatment groups except Vitamin
E treated group and from 30th
day of treatment and maintain rota rod performance when compared to the
control group (fig. 4).
Atorvastatin 50mg/kg did not maintain the Atorvastatin decreased Rota rod performance when compared to
Atorvastatin treatment group. Vitamin E 100 and 200mg/kg treatment significantly increased (P<0.01 and P
< 0.001) , maintained the Atorvastatin impaired Rota rod performance from 30th
day when compared to the
Atorvastatin treatment group (fig.4 ).
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Table 4: Effect of chronic treatment Atorvastatin, vitamin E and Atorvastatin + vitamin E on Rota
Rod performance
Group
No.
Treatment mg/kg Rota Rod Performance (days)
0 15 30 45
1. Control 120 ±
0
120 ± 0 120 ± 0 120 ± 0
2. Atorvastatin (10 mg/kg) 120 ±
0
111.6 ± 9.343 112 ± 16.793c 2b 3b
90 ± 10.886 c2c
3. Vitamin E (100 mg/kg) 120 ±
0
120 ± 0c 120 ± 0
1b 120 ± 0
4. Atorvastatin (10 mg/kg) + vitamin
E
(50 mg/kg)
120 ±
0
59.8 ± 24.284 70.6 ± 34.480c 96.2 ± 15.023
b 2a
1c
5. Atorvastatin (10 mg/kg) + vitamin
E
(100 mg/kg)
120 ±
0
90 ± 10.886c 112 ± 16.973
a 1c
3b
120 ± 0 1c 3b
6. Atorvastatin (10 mg/kg) + vitamin
E
(200 mg/kg)
120 ±
0
114.4 ±
12.522a
116.2 ± 6.943 1b
120 ± 0 1c
Fig. 4: Effect of chronic treatment ofAtorvastatin, vitamin E and Atorvastatin + vitamin E on Rota Rod
performance
Note: Values expressed as mean ± SD (N=5)
a, p<0.05; b p<0.01; c p<0.001 vs control group
1a, p<0.05; 1b p<0.01; 1c p<0.001 vs atorvastatin group
2a, p<0.05; 2b p<0.01; 2c p<0.001 vs vitamin E group
3a, p<0.05; 3b p<0.01; 3c p<0.001 vs ator + vitamin E (50 mg/kg)
4a, p<0.05; 4b p<0.01; 4c p<0.001 vs ator + vitamin E (100 mg/kg)
5a, p<0.05; 5b p<0.01; 5c p<0.001 vs ator + vitamin E (200 mg/kg)
(2 WAY ANOVA) followed by TUKEY-KRAMER multiple comparison test
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SUPEROXIDE DISMUTASE:
Chronic Atorvastatin 10mg/kg treatment significantly decreased (P<0.001) the Super oxide dismutase levels
in all treatment groups except Vitamin E treatment group when compared to control group (fig - 5).
Vitamin E 50mg/kg treatment did not increased the Atorvastatin decreased Super oxide dismutase levels
when compared to the Atorvastatin treatment group. Where as Vitamin E 100 and 200mg/kg treatment
significantly increased (P<0.01( and (P< 0.01). Super oxide dismutase levels respectively when compared to
the Atorvastatin group. (fig - 5).
Table 5: Effect of Chronic Treatment of Atorvastatin, Vitamin-E and Atorvastatin and Vitamin-E on Super
Oxide Dismutase Levels
S.No Groups SOD (IU/ml)
1 Control 33.43.782 2 2a 1c 3c 4c
2 Vitamin E 100 mg/kg 25.83.114 a1c3b
3 Atorvastatin 10mg/kg 7.82.049 c2c 4b 5c
4 Atorvastatin +50mg/kg vitamin E 54.583
c 2b 5c
5 Atorvastatin +100mgkg vitamin E 19.43.286 c 1b 5a
6 Atorvastatin+200mg/kg vitamin E 27.64.879 1c 3c 4a
Fig 5: Effect of Chronic Treatment of Atorvastatin, Vitamin-E and Atorvastatin and Vitamin-E on Super
Oxide Dismutase Levels
Note: Values expressed as mean SD (N=5)
a, p<0.05; b p<0.01; c p<0.001 vs Control Group
1a, p<0.05; 1b p<0.01; 1c p<0.001 vs Atorvastatin Group
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2a, p<0.05; 2b p<0.01; 2c p<0.001 vs Vitamin – E Group
3a, p<0.05; 3b p<0.01; 3c p<0.001 vs Ator + Vit – E (50 mg/kg)
4a, p<0.05; 4b p<0.01; 4c p<0.001 vs Ator + Vit – E (100 mg/kg)
5a, p<0.05; 5b p<0.01; 5c p<0.001 vs Ator + Vit – E (200 mg/kg)
(2 WAY ANOVA) followed by TUKEY-KRAMER multiple comparison test
CATALASE:
Chronic Atorvastatin 10mg/kg treatment significantly decreased (P<0.001) the catalase levels in all
treatment groups except Vitamin E treatment group when compared to control group. (fig- 6).Vitamin E
50mg/kg treatment did not increase the Atorvastatin decreased Catalase levels when compared to the
Atorvastatin treatment group. Whereas Vitamin E 100 and 200mg/kg treatment significantly (P<0.001) the
Catalase levels respectively when compared to Atorvastatin group. (fig-6).
Table 6: Effect Chronic treatment of Atorvastatin, Vitamin-E and Atorvastatin + Vitamin -E on Catalase
Levels
S.No Groups Catalase(µmoles/mg/min)
1 Control 5.944 ± 0.4451 3c 4b 5a
2 Vitamin E 100mg/kg 4.38 ± 0.7338 b 1c 3c
3 Atorvastatin 10mg/kg 1.2244 ± 0.3558 c 2c 4c 5c
4 Atorvastatin+50mg/kg vitamin E 2.145 ±0.6971 c 2c 4b 5c
5 Atorvastatin +100mg/kg vitamin E 3.492 ± 0.4798 c 1c 3b 5b
6 Atorvastatin +200mg/kg vitamin E 4.876 ± 0.4451 a 1c 3c 4b
Fig 5: Effect of Chronic Treatment of Atorvastatin, Vitamin-E and Atorvastatin and Vitamin-E on Catalase
Levels
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Note: Values expressed as mean SD (N=5)
a, p<0.05; b p<0.01; c p<0.001 vs Control Group
1a, p<0.05; 1b p<0.01; 1c p<0.001 vs Atorvastatin Group
2a, p<0.05; 2b p<0.01; 2c p<0.001 vs Vitamin – E Group
3a, p<0.05; 3b p<0.01; 3c p<0.001 vs Ator + Vit – E (50 mg/kg)
4a, p<0.05; 4b p<0.01; 4c p<0.001 vs Ator + Vit – E (100 mg/kg)
5a, p<0.05; 5b p<0.01; 5c p<0.001 vs Ator + Vit – E (200 mg/kg)
(2 WAY ANOVA) followed by TUKEY-KRAMER multiple comparison test
GLUTATHIONE:
Atorvastatin 10mg/kg treatment significantly decreased (P<0.001) the Glutathione level in all treatment
groups except Vitamin E treatment group. When compared to control group. (fig-7 ).
Vitamin E 50mg/kg treatment did not increase the Atorvastatin decreased Glutathione levels when compared
to Atorvastatin treatment group. Whereas Vitamin E 100mg/kg and 200mg/kg treatment significantly
increased (P<0.01) and (P<0.001) the Glutathione levels respectively when compared to the Atorvastatin
treatment group (fig-7 ).
Table 7: Effect Chronic treatment of Atorvastatin, Vitamin-E and Atorvastatin + Vitamin -E on Glutathione
Levels
S.No Groups Glutathione (mg/dl)
1 Control 199 ± 57.922 1c 3c 4a
2 Vitamin E 100 mg/kg 229.8 ± 58.611 1c 3c 4b
3 Atorvastatin 10mg/kg 11.6 ± 1.700 c 2c 4a 5c
4 Atorvastatin+50mg/kg vitamin E 16.38 ± 2.574 c 2c 4a 5c
5 Atorvastatin +100mg /kg vitamin E 105.4 ± 23.458 a 1a 2a 3a
6 Atorvastatin+200mg/kg vitamin E 228 ± 55.082 1c 2c 3c 4b 5b
CONCLUSION
The results of the present study showed that, chronic treatment with Atorvastatin produce
Neuropharmacological and Biochemical alterations such as decreased body weight, exploratory behavior,
loco motor activity, motor co –ordination, muscle grip strength and depression . Decrease in levels of
antioxidant enzymes. This may support the proposed contribution of oxidative injury in exacerbating
Neuropharmacological, Biochemical alterations induced by atorvastatin. The results of the present study
indicate thatAtorvastatin prescription requires monitoring or cholesterol levels, as it may lead to
Neuropharmacological alterations. Vitamin E Supplementation decreased Atorvastatin induced
Neuropharmacological and severe side effects the increasing anti-oxidant enzymes SOD, CAT, gultathion,
Dose dependently. Vitamin E used as nutritional supplement, it is a powerful biological antioxidant and is
the principle membrane-associated antioxidant molecule in mammals. It plays a major role in preventing
oxidative damage by scavenging free radicals.
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Note: Values expressed as mean SD (N=5)
a, p<0.05; b p<0.01; c p<0.001 vs Control Group
1a, p<0.05; 1b p<0.01; 1c p<0.001 vs Atorvastatin Group
2a, p<0.05; 2b p<0.01; 2c p<0.001 vs Vitamin – E Group
3a, p<0.05; 3b p<0.01; 3c p<0.001 vs Ator + Vit – E (50 mg/kg)
4a, p<0.05; 4b p<0.01; 4c p<0.001 vs Ator + Vit – E (100 mg/kg)
5a, p<0.05; 5b p<0.01; 5c p<0.001 vs Ator + Vit – E (200 mg/kg)
(2 WAY ANOVA) followed by TUKEY-KRAMER multiple comparison test
REFERENCES
1. Apple by J. Druy Spending surged 17% lest year: figure has nearly doubled in 4 years. USA Today
2002; A1.
2. Zureik M, Courbon D, Ducimetiere P. serum cholesterol concentration and death from suicide in men:
Paris prospective study I. BMJ .1996: 649-651.
3. Blatt DH, Leonard SW, Traber MG. Vitamin E kinetics and the function of tocopherol regulatory
proteins. Nutrition. 2001: 17:799-805.
4. Traber MG, Shils ME, Olson JA, Shike M, Ross AC. Modern Nutrition in Health and Disease. 10th
ed.
Baltimore: Williams & Wilkins, 1999: p.347-62.
5. Pierno S, DeLuca A, Tricarico D et. Al. Potential risk of Myopathy by HMG- COA reductase inhibitors:
a comparison of Pravastatin and simvastatin on membrane Electrical properties of rat skeletal Muscle
Fibres. JI. Pharmacol. Exp Ther. 1995: 275(1); 190-196.
6. King DS, Jones DW, Wofford MR et al. cognitive impairment associated with Atorvastatin and
simvastatin pharmacotherapy. 2003: 23 (12); 1663-1667.
7. Mortensen SA, Leth A, Agnes E, Rohole M. Dose- related decrease of serum coenzyme Q10 during
treatment with HMG-COA reductase inhibitors. Mol Aspects Med. 1997: 18; 5137-5144
RESEARCH ARTICLE e-ISSN: 2454-7867
Prasanna Kumar B et al. Int J Trends in Pharm & Life Sci. 2015: 1(5);600-612 . 612
8. Orsi A, Sherman O, Wolderelassiez. Simvastatin Associated memory loss. Pharmacotherapy. 2001: 21;
761 –769.
9. Kulkarni SK. Hand book of experimental pharmacology, Vallabh Prakashan, New Delhi, pp 148-50;
1999.
10. Vogel HG. Drug discovery and evaluation: Pharmacological assays .2002:p669-774
11. Reitman S, Frankel S. A method of assaying liver enzymes in human serum. American Journal of
Clinical Pathology. 1957: 28; 56 – 58.
12. Beers RF. (1951). Thesis, Massachusetts Institute of Technology
13. Ellman GL. Tissue sulfhydryl Groups. Archives of biochemistry and biophysics. 1959: 82; 70-77.