الفهرس 
BACKGROUND OF STATINS
MECHANISM OF ACTIONOnly 14 pages are availabe for public view
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Abstract
Hyperlipidemia is a metabolic disorder characterized by
excess of lipid substances as cholesterol and triglycerides, in the
blood. Its complications such as atherosclerosis, myocardial
infarction, stroke and peripheral vascular diseases remain
important reasons of mortality and morbidity in all countries.
Drugs commonly used to treat high cholesterol level are statins
including atorvastatin (Lipitor®). According to Med Ad News
(Medical Advertising News), the two top selling drugs are
Lipitor® and Zocor®. Atorvastatin reduces the levels of ”bad”
cholesterol (LDL) and triglycerides in the blood, while
increasing levels of ”good” cholesterol (HDL).
Accordingly, the aim of the present study was designed to
determine the potential toxicity of the therapeutic doses of
atorvastatin in male albino rats. A total of twenty five adult
male albino rats were divided randomly into five groups.
The control group (group 1) did not receive any
medication, while group II and group III received atorvastatin
(10 mg/kg/day for two and four weeks respectively). group IV
and group V were left for one month after the last dose for
recovery from the drug.
Muscle, kidney and liver biopsies were taken from each rat
for histopathological and ultrastructural examinations. In comparison with respective control rats, the results showed
muscular changes in the form of; splitting of myofibers with a
decrease in muscle fibers thickness, cellular infiltration, and
intramuscular edema. Fragmentation of sarcoplasm with centrally
located nuclei, necrosis of myocytes and unrecognized striation of
muscle fibers were also observed in treated groups. Electron
microscopy studies revealed degenerated myofibrils,
mitochondrial vacuolation with destructed cristae, and streaming
of Z-line. The results also showed slight effects of atorvastatin on
the kidney of rats which was in the form of vacuolization,
degeneration and cloudy swelling of epithelial cells in the tubules
with the formation of cell debris inside the lumen of proximal
convoluted tubules, and diminish in urinary space of glomeruli.
Moreover, hypercellulatry and congestion of glomeruli were also
detected. Atorvastatin led to the severe degeneration of
hepatocytes, in the form of congestion of central vein and
sinusoids, as well as dilatation of the central vein and sinusoids,
edema, ballooning degeneration of hepatocytes, and activation of
Kupffer cells. Some ultrasructural changes included intracellular
edema, and degeneration of bile canaliculi with reduced number
of their microvilli. All of these results may suggest that
atorvastatin had the potential for induce direct effects on the
structure and function of muscles, kidneys and liver of rats.