THERAPEUTIC BENEFITS OF VERAPAMIL IN ADJUVANT ARTHRITIS AND ITS POTENTIAL APPLICABILITY AS A RENAL PROTECTIVE AGENT
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In view of the role of Ca ions in the inflammatory process and lymphocytes proliferation, the study was carried out to evaluate the effect of verapamil, a calcium channel blocker (CCB), alone or in combination with indomethacin on the course of adjuvant arthritis. The study was also extended to demonstrate the potential applicability of verapamil as a renal protective agent. A model of adjuvant arthritis was created by single intradermal injection of 0.1 ml of Freund's complete adjuvant in the base of the rat tail. 50 rats were divided into 5 equal groups, the 1st group was normal control rats, the 2nd group was arthritic non treated control rats, the 3rd, 4th and 5th groups were arthritic rats received verapamil (5 mg/kg/day orally), indomethacin (2 mg/kg/day/orally), and combination of verapamil + indomethacin (in the same previously mentioned doses) respectively for 30 days. The results revealed that verapamil induced significant reduction (P < 0.001) of the mean values of hind paws thickness of the arthritic rats. The percentage reduction of the hind paws swelling of the arthritic rats induced by verapamil, indomethacin and their combination were 57.5%, 80.1% & 92.5% respectively. On the other hand, administration of indomethacin alone for 30 days induced significant increase in serum urea and serum creatinine concentrations (P < 0.001) of the arthritic rats as well as evident renal histopathological changes. When verapamil was combined with indomethacin, no significant changes were observed in both serum urea and creatinine concentrations as well as the histopathological changes in the rat kidney became very mild. In conclusion: verapamil has an evident • antiinflammatory and antirheumatic activity. Furthermore, it augments the antiinflammatory activity of indomethacin. Moreover,verapamil may protects against indomethacin induced nephrotoxicity.