R KUMAR, M SHARMA, J PURI, I JAIN, S SINGH, K KAPOOR, N ANSARI, S SINGH
R KUMAR, M SHARMA, J PURI, I JAIN, S SINGH, K KAPOOR, N ANSARI, S SINGH. Effect of Hypolipidemic drugs on stress induced alteration on Lipid profile in rats. The Internet Journal of Pharmacology. 2009 Volume 8 Number 1.
Modern life is full of stress because of many factors. Emotional and other physical stress factors affect the normal physiological system of the body. Hans Selye1 defined stress as the reaction of an organism to various stimuli. Stress can be considered as a state of a disharmony or threatened homeostasis. Stressful stimuli may influence the onset and progression of a number of disorders in human being leading to hypertension, diabetes, stroke, cancer depression etc.2,3. Cardiovascular system is more prone to be affected by stress, either directly or indirectly4. Presently cardiovascular accidents are the major killer. There are various reports that stress can change the level of certain hormones like insulin, cortisol and epinephrine5-7. All these hormone affect lipid profile of the body to a great extent. In animal studies it was found that stress raises serum and tissue cholesterol level of rats on normal diet8. Berger
Materials And Methods
Group I – Control, Group II and Group III treated with gemfibrozil and bezafibrate respectively. In control group animals were treated with 0.5 ml normal saline (p.o.) daily from day 1 to day 22. Serum lipid levels were estimated on day O (blank control) and on day 22 after stress (positive control). In group II and III animals were treated with gemfibrozil 1000 mg/kg and bezafibrate 500 mg/kg body weight (p.o.) respectively daily from day 1 to day 22. Serum lipid levels were estimated on day 3,7,14 and 21 and on day 22 after stress.
Gemfibrozil (1000 mg/kg p.o.) on normal diet reduced the TC from 84±1.87 to 73.68±1.33 p<0.01, raised the HDLC from 35.2±1.03 to 38.0±0.68 p<0.05, reduced the TG from 54.81±1.81 to 38.51±1.36 p<0.001, reduced the LDLC from 37.83±1.34 to 27.97±0.81 p<0.01, and reduced the VLDLC from 10.26±0.36 to 7.70±0.25 p<0.001 (table I group II versus group I). Similarly bezafibrate (500 mg/kg p.o.) reduced the TC from 84±1.87 to 71.88±0.53 p<0.001, raised the HDLC from 35.2±1.03 to 38.56±0.41 p<0.01, reduced the TG from 54.81±1.81 to 38.6±0.69 p<0.001, reduced the LDLC from 37.83±1.34 to 25.58±0.54 p<0.001 and reduced the VLDLC from 10.26±0.36 to 7.74±0.17 p<0.001 (table I group III versus group I). In group II and group III when compared to blank control gemfibrozil (1000 mg/kg po) and bezafibrate (500 mg/kg p.o) reduced the serum lipid levels in rats significantly except the HDL cholesterol which increased significantly.
After stress in control group TC increased from 84±1.87 to 113.33±1.36 p<0.001, HDLC reduced from 35.2±1.03 to 34.83±0.74 p>0.05, TG increased from 54.81±1.81 to 77.03±1.81 p<0.001, LDLC increased from 37.83±1.34 to 63.09±1.14 p<0.001 and VLDLC increased from 10.96±0.36 to 15.40±0.36 p<0.001 (table I and table II control group). In control group stress increased the lipid levels in rats significantly except HDL cholesterol which reduced insignificantly.
When drug treated animals subjected to stress on day 22, their serum lipid levels increased significantly except HDL cholesterol which reduced significantly (table I and table II). After stress in gemfibrozil treated rats TC increased from 73.68±1.33 to 96.11±1.37 p<0.001, HDLC reduced from 38.0±0.68 to 34.22±0.56 p<0.01, TG increased from 38.51±1.36 to 53.33±1.13 p<0.001, LDLC increased from 27.97±0.81 to 51.23±1.14 p<.001, and VLDLC increased from 7.70±0.25 to 10.67±0.18 p<0.001 (table I and table II group II). Similarly after stress in bezafibrate treated rats TC increased from 71.88±0.53 to 94.36±0.51 p<0.001, HDLC reduced from 38.56±0.41 to 37.22±0.40 p<0.05, TG increased from 38.6±0.69 to 52.26±0.92 p<0.001, LDLC increased from 25.58±0.54 to 47.7±0.86 p<0.001 and VLDLC increased from 7.74±0.17 to 10.45±0.19 p<0.001 (table I and table II group III).
When compared to positive control serum lipid levels were significantly less in gemfibrozil treated rats and bezafibrate treated rats except HDL cholesterol which reduced insignificantly in gemfibrozil treated rats and increased significantly in bezafibrate treated rats (table II group II & III versus group I).
Hans Selye1 defined stress as the reaction of an organism to various stimuli. Stressful stimuli may influence the onset and progression of a number of disorders in human being leading to hypertension, diabetes, stroke, cancer depression etc.2,3. Swimming and force water swimming in small laboratory animals has been widely used for studying the physiological changes and the capacity of the organism in response to stress19.20. Swimming is not always a simple exercise stress because emotional factors are difficult to eliminate21.
In the present experimental study our findings were comparable to the observations of certain other workers8-10 with regard to effect of stress on serum lipid levels. Hypolipidemic drugs gemfibrozil and bezafibrate which are fibric acid derivative and act by increasing lipoprotein lipase activity. Other mechanism as well22 not only reduced raised lipid levels but also reduced normal lipid levels. Observations also suggest that bezafibrate alter serum lipid levels more significantly than gemfibrozil. During treatment with hypolipidemic drugs serum lipid levels were estimated on day 3, 7, 14 and on day 21. The serum lipid values estimated on day 14 and on day 21 were statistically similar. Therefore serum lipid levels estimated on day 21 were included for analysis. Serum lipid levels were increased after physical stress of 5 hours swimming on day 22 in all the rats (group I, II and III). This confirmed the previous reports by Berger
It can be concluded that gemfibrozil (1000mg/kg p.o.) and bezafibrate (500mg/kg p.o.) are not only hypolipidemic but also effective in attenuating stress induced dyslipidemia in rats.