Antirheumatic and Antioxidant Effect of Combination Therapy of Methotrexate and Carnosic Acid in Experimental Arthritis.

In this study we investigated the potential antioxidant effect of carnosic acid and its combination with methotrexate (MTX) on mRNA expression of catalase (CAT) and heme oxygenase 1 (HO-1) in the liver as key parameters of oxidative stress in rat adjuvant arthritis (AA). We also examined arthritic score (AS) as representative clinical parameter monitored in this animal model. MTX was administrated in a subtherapeutic dose twice a week of 0.3 mg/kg b.w. The carnosic acid (CA) was administered daily in a dose of 100 mg/kg b.w., alone and in combination with MTX (CA+MTX). CA and MTX were administrated orally by gastric gavage. Plasma samples were collected on the 28th experimental day and used for PCR determination. The 28th experimental day was also used for AS analysis. We observed a significant decrease of CAT expression in the liver in the nontreated AA animal group, which indicated successful induction of AA. In MTX and CA groups, we did not observe any significant increment of CAT, but in the group with combination therapy, there was a significant increase of CAT expression compared to the AA group and to the MTX group itself. Expression of HO-1 was significantly increased in the AA group compared to the control group. MTX and CA groups did not significantly improve the levels of HO-1, but in CA+MTX we observed a significant decrease compared to the AA group. In the clinical parameter AS, we observed a very similar result as with markers of oxidative stress, meaning that CA+MTX was the only group that significantly lowered AS compared to the AA group. Monotherapy with CA as well as with MTX had no significant effect in our experiment on all evaluated parameters. Combination of CA and MTX has been proven to be more efficient than MTX in monotherapy, which might have promising effects in reducing side effects of MTX treatment by lowering the dose of MTX. [ABSTRACT FROM AUTHOR]