Pleiotropic effects of rimonabant and simvastatin on obesity associated multiple metabolic risk factors in rats.
BACKGROUND
Obesity, a worldwide health problem, is a metabolic disease currently associated with a cluster and progressive pathologies presenting several features of metabolic syndrome.


OBJECTIVE
The present study was undertaken to investigate the effect of rimonabant, simvastatin and their combination on obesity associated metabolic disorder mediators in adult male rats.


METHODS
Fifty adult male Wistar rats weighing (120 +/- 10 g) were divided into five groups: Group 1 was kept on standard rodent chow and served as normal diet control. Group 2 was given high fat diet (HFD) for twenty weeks and served as HFD control. Groups 3, 4 and 5 administered HFD for ten weeks and then orally received rimonabant (2 mg/kg/day), simvastatin (10 mg/kg/day), combination of both drugs, respectively for another ten weeks with continuing feeding HFD.


RESULTS
The current results showed that the treatment of HFD rats with either rimonabant or simvastatin significantly reduced body mass index, total cholesterol, triacylglycerides, low density lipoproteins, tumor necrosis factor alpha and monocyte chemoattractant protein-1, while increased adiponectin serum levels. Rimonabant showed to be more effective than simvastatin. Moreover, concomitant administration of rimonabant and simvastatin achieved the highest effect which nearly normalized most of the studied parameters as compared to singular therapy.


CONCLUSIONS
Rimonabant is the drug of primary choice as singular therapy for obesity. The adjunct therapy of rimonabant with simvastatin may be a novel and a promising therapeutic approach as it has a beneficial effect on the pathophysiological processes of obesity and its associated metabolic disorders.
Department of Narcotics, Ergogenic Aids and Poisons, National Research Centre, Cairo, Egypt. dr_nsalem@yahoo.com
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Salem
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Assaf
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Ahmed
D000818:Animals; D018932:Chemokine CCL2 / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077285:Rimonabant; D012307:Risk Factors; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D008055:Lipids; D010880:Piperidines; D011720:Pyrazoles; D014409:Tumor Necrosis Factor-alpha; D019821:Simvastatin; D000077285:Rimonabant