PRECLINICAL SCREENING
MODEL OF
ANTI-HYPERLIPIDEMIC AGENTS
PREPARED BY :-
Harsh K. Patel (20022411051)
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WHAT IS DYSLIPIDEMIA ?
• Dyslipidemia is a medical condition that refer to abnormal level of blood lipid.
• The most common type of dyslipidemia or high lipid level.
• Dyslipidemia can affect any lipid parameter
Including: LDL cholesterol level
HDL cholesterol level
• Two categories :- primary dyslipidemia
secondary dyslipidemia
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CAUSE OF DYSLIPIDEMIA
• Primary dyslipidemia :- abnormal lipid level that are caused by a mutated
gene or genes inherited from one or both parents.
• Secondary dyslipidemia :- is more common and occur due to a variety of
factor including :-
- Poor or high fat, high sugar diet, lack of excercise
- Alcohol abuse
- Cigarette smoking
- Liver disease
SCREENING MODELS
IN VIVO MODELS IN VITRO MODELS
• Tritan Wistar rat induced hyperlipidemia • Inhibition of isolated HMG- COA
• Cholesterol diet induced atherosclerosis
reductase inhibitors
in rabbits
• ACAT inhibitory model
• Hereditary hyperlipidemia in rabbits
• Hereditary hypercholesteromia in rats
• Transgenic animal model
• Hypolipidemic activity in Syrian hamsters
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IN VIVO MODELS
(1) Tritan Wistar rat induced hyperlipidemia
Purpose :-
The systemic administration of the surfactant triton to rats results in a biphasic
elevation of plasma cholesterol and triglycerides.
Requirements :-
Chemicals : Surfactants, Triton
Animals : Wistar strain male albino rats
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Rats are divided into 7 groups such that each group contains 6 rats and kept in cages 5 days
prior to dosing
The animals are starved for 1 8hr with 10% aqueous solution of triton at 400mg /kg body
weight given i.p The test drugs and the solvent for control is administered simultaneously
with triton injection.
After administration of triton, blood is collected by retro orbital puncture under ether
anesthesia and subjected to centrifugation to obtain serum after 24hr and 48hr
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Evaluation
• Serum is analyzed for serum triglyceride, serum total cholesterol, Serum high
density lipoprotein cholesterol, Serum low density lipoprotein cholesterol,
serum very low density lipoprotein cholesterol, serum glucose.
• The result will be evaluated by ANOVA test and Dunnet Multiple comparision
test.
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(2) CHOLESTEROL-DIET INDUCED ATHEROSCLEROSIS
IN RABBITS
Purpose
Rabbits are known to be susceptible to hypercholesterolemia and arteriosclerosis
after excessive cholesterol feeding. Therefore, this approach has been chosen by to study
the effect of potential anti-arteriosclerotic drugs.
Requirements
Animals: White New Zealand male rabbits.
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Procedure
Group of male rabbits(standard and control) at an age of 8-10 weeks are used and blood is withdrawn
from the marginal ear vein for determination of total cholesterol, total glycerides, and blood sugar.
The rabbits are switched from commercial food to a diet supplemented with 0.3-2% cholesterol and
kept on this regimen for a period of 10-12 weeks.
One group is kept on normal diet. During and at the end of the experiment blood is taken for
analysis.
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The animals are sacrificed and the thoracic aorta is removed, cleaned of surrounding
tissues, and longitudinally cut and opened for fixation with formaldehyde.
The tissue is stained with oil red. In animals fed a normal diet, the aorta does not
show any staining, whereas in cholesterol-fed rabbits the aorta shows severe
atherogenic lesions.
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Evaluation
• The percentage of the intimal surface covered by the oil red positive lesions is
calculated with a computerized plan meter.
• Statistical evaluation is performed by Dunnett's or Scheffe's test.
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