الفهرس | Only 14 pages are availabe for public view |
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. |