Abstract:
Rheumatoid Arthritis (RA) is an autoimmune disease having a global importance. The
role of disease modifying anti-rheumatic drug (DMARD) Leflunomide has been
described in case of RA. The objective of this study was to characterize the anti oxidant property of leflunomide. The second major objective of this study was to
improvise the efficacy of Leflunomide and reduce the cyto-toxicity by using Folic
acid in-vivo. The anti-oxidative property was studied by performing DPPH assay. The
anti-oxidative potential of leflunomide was shown by significant DPPH inhibition
(p<0.05).
A BALB/c collagen induced arthritic model was designed and characterized via
histopathological changes and gross morphological changes. The treatment started
showing improvement in joints after the second dose of the drug. The maximum
improvement was shown in the group with dosage 17 mg LEF/kgBW/day along with
3mg folic acid/kgBW/day. Spleen indices showed a significant decrease in the size
and inflammation of the spleen in the models taking Leflunomide alone with folic
acid. No significant change was seen by increasing the dose of drug and supplement
in this case. Pathological changes in the joints of paws were studied through
histopathology analysis. In case of treatment groups where Leflunomide was
supplemented with folic acid, it was observed that inflammation in synovium and
hyperplasia was reduced. The cartilage and bone erosion was observed to be reduced.
Immunohistochemistry was performed to check the levels of the mitochondrial
proteins like dihyrooratate dehydrogense (DHODH) and Tyrosine kinase in the spleen
cells of arthritic models. It was observed that the levels of these proteins were
decreased in treated groups.
