The HMG-CoA Reductase Inhibitor "Atorvastatin" Reduces Air Pouch Inflammation by Different Mechanisms
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- Category: Vol. 80, September 2012
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The HMG-CoA Reductase Inhibitor "Atorvastatin" Reduces Air Pouch Inflammation by Different Mechanisms,AMANI N. SHAFIK, HISHAM A. AWAD, MOSTAFA M. KHODEIR and JAMAL M. DAMMONA
Abstract
Background and Study Aims: Statins represent a well-established class of drugs prescribed for the treatment of hypercholesterolemia. Several reports have described the ability of statins to suppress acute and chronic inflammation. The aim of this study was to determine the mechanisms of the anti-inflammatory effect of atorvastatin in the rat air-pouch model of inflammation.
Material and Methods: Carrageenan air-pouch model of inflammation was induced in rats. The animals were assigned to three groups: Normal control, air pouch inflammation and normal rats used to study the effects of atorvastatin on beta-receptor. Half of the rats were scarified after 1 day and the others continued for 7 days after carrageenan injection. The serum C-reactive protein was measured. Exudates were col-lected for measurement of tumour necrosis factor alpha, total leucocytic count and exudates volume. ECG parameters were recorded. The pouch and granulation tissue were dissected and histopathologically examined.
Results: Atorvastatin improved all inflammatory param-eters measured. Combined treatment of atorvastatin with mevalonate or propranolol showed significant reduction in the anti-inflammatory effect of atorvastatin. A reduced response to propranolol on ECG parameters in rats with both acute and chronic inflammation was observed. In addition, atorvastation did not reverse the reduction in response to propranolol as evidenced by ECG parameters. As regards histopathological scoring, anti-inflammatory effect of atorvastatin was proved by significant reduction in its recorded scores. This anti-inflammatory effect was counteracted by co-treatment with mevalonate or propranolol as shown in higher recorded scores that reached significant levels compared to atorvastatin alone.
Conclusions: The current study provided insights for anti-inflammatory effect of atorvastatin in acute and chronic air pouch model of inflammation and the possible involvement of the mevalonate pathway, vascular permeability and beta receptors in the inflammatory mechanism.