The Effect of Different Dosage Regimens of Roxithromycin on its Anti-Inflammatory Activity and Possible Mechanisms of Action in Acute Pleurisy and Chronic Arthritis in Rats
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- Category: Vol. 79, June 2011
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The Effect of Different Dosage Regimens of Roxithromycin on its Anti-Inflammatory Activity and Possible Mechanisms of Action in Acute Pleurisy and Chronic Arthritis in Rats,AMANI N. SHAFIK, SOHEIR A. DIAB, EMAN A. ABD EL-RASHEED, HANAN FOUAD, SAFENAZ SALAH EL-DIN and EMAN H. ABD EL-RAHMAN
Abstract
Many of the steps in the inflammatory cascade are reported to be controlled by soluble regulatory molecules (serotonin, histamine and leukotriene, etc.) known as inflammatory or chemical mediators. Furthermore, much evidence clearly shows that T cells play a pivotal role in initiation, driving and maintenance of all these processes by elaboration of several types of cytokines. Several studies have shown that long-term administration of macrolide antibiotics can favorably modify the clinical condition of inflammatory diseases. Although the precise therapeutic mechanisms of macrolides are not well understood, Roxithromycin, a macrolide with better plasma concentrations and higher tissue concentrations was tested in an acute and chronic rat animal models of inflammation.
Aim: The aim of the present study was to elucidate the effect of different dosage regimens of roxithromycin on its anti-inflammatory activity and possible mechanism of action in experimental models of acute pleurisy and chronic arthritis in rats.
Methods: Male albino rats were subjected to two different models of inflammation. Acute pleurisy was induced by injecting carrageenan into the pleural cavity of the rat. One hour before carrageenan injection and 24 and 48h thereafter, rats were given roxithromycin in single oral daily ascending dosage schedule of 2.5, 5, 10, 20 and 40mg/kg. Control group received only distilled water. The animals were sacrificed 72 hours after carrageenan and the pleural fluid was aspirated, its volume, total and differential cell count and TNF-a levels were measured.
Chronic soft tissue inflammation and arthritis were induced by injecting formalin into the subplantar region of the left hind paw of the rat on day 1 and day 3 of the experiment. Rats were treated with roxithromycin in the same previous single oral daily doses for the whole length of the experiment 21 days. The increase in the paw volume of each treated group was measured using Digital Plethysmometer. Blood samples were collected for measurement of serum TNF-a level. One day before formalin injection and on the 21st day of formalin injection, the left hind paw was imaged antero-posteriorly by X-ray. On the 21st day the animals were sacrificed and their left hind paws were excised for histopathological examination.
Results: Administration of roxithromycin in a dose of 2.5mg/kg/day resulted in insignificant changes neither in acute nor chronic inflammation; while 5, 10, 20 and 40mg/ kg/day significantly reduced the pleural exudate volume, the total leukocyte number and the TNF-a level in the pleural exudates. Also roxithromycin in previous doses attenuated the increase in paw volume, serum TNF-a level and the signs of inflammation; soft tissue edema, joint deformity and destruction were correlated dose dependently with maximum response observed on day 21.
Conclusion: Roxithromycin has anti-inflammatory activity in the models of acute carrageenan pleurisy and chronic formalin-induced arthritis dose dependently with maximum response on day 21. Macrolides affect several pathways of the inflammatory process, including the prostaglandins for-mation, the migration of neutrophils and the production of proinflammatory cytokine TNF-a.