EFFICACY AND NEPHROTOXICITY OF CYCLOSPORINE ALONE AND ASSOCIATED WITHMETHYLPREDNISOLONE IN ADJUVANT ARTHRITIS

In this work we studied the efficacy and the renal toxicity of cyclosp orin (CsA) administered alone and in association with methylprednisolo ne (MTP) to rats during the development of adjuvant arthritis, in comp arison with a classical NSAID. Daily oral administration of all drugs markedly inhibited arthritis development until the end of the study pe riod, with a range in percentage of inhibition from 76.6 (indomethacin ) to 89.7 (CsA+MTP). N-acetyl-beta-D-glucosaminidase (NAG) urinary lev els in arthritic rats and in rats treated with indomethacin and MTP we re similar to those of controls; the administration of CsA strongly en hanced NAG excretion during the whole period, while the association wi th MTP reported the values similar to controls at day 21 from arthriti s induction (8.92 +/- 3.71 U/L vs 6.88 +/- 2.15 U/L). The levels of pl asma CsA resulted reduced by treatment with MTP (195.0 +/- 42.37 ng/ml vs 366.7 +/- 118.36 ng/ml). Our results indicate a protective action of MTP towards CsA nephrotoxicity, according to a decrease in CsA plas ma concentrations, and an increased therapeutic efficacy until the end of treatment, even if a decrease in growth of animals treated with MT P was observed.