This work was carried out in order to compare the effect of lefiunomide,
methotrexate and their combination in the treatment of adjuvant induced
arthritis in rats.
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 leflunomide (at a loading
dose of 45mg/lcg orally for 3 drys, followed by 9mg/kg/dcty orally), methotrexate
(0.75 mg /Kg 11W once weekly) and combination of lefiurtomide +
methotrexate (in the same previously mentioned doses) respectively. One
month after initiation of the treatment the results revealed that: lefiunomide,
methotrexate and their combination signcantly (P<0.001) reduced
the mean volt /Ps of the hind paws thickness of the arthritic rats and the
percentage reduction of the hind paws swellings were 9096. 64.09 and
96.07% respectively . Furthermore, lefiunomide, methotrexate and their
combination significantly (P<0.001) increased the mean values of the hind
paws pressure shresholds of the arthritic rats and the percentage increase
of the pressure thresholds were 89.52%, 69.8% and 97.75% respectively
. These results were also confirmed by the histopathological examination
of the ankle joints of the different groups, lefiunomide was
superior to methotrexate in the repair of the destructive lesion, meanwhile
the combination therapy showed marked improvement in the repair process
than that observed by each drug alone . Treatment with leflunomide.
methotrexate or their combination did not induce any significant changes
in H896, total RBCs count, platelets count, serum urea and creatinine and
total serum bilirubirt, meanwhile there were signcant decreases in the
total WBCs counts and significant increases in liver enzymes (SCOT &
SGPT). No differences were observed in all the tested haPmatological
and biochemical parameters between the group treated by the combination
of leflunomide and methotrexate and the groups treated by leflunomidy
or methotrexate separately. The histopathological examination
of the kidneys and livers supported the previous results. In conclusion,
leflunomide is superior to methotrexte in the treatment of adjuvant arthritis
and their combination offers additional efficacy while remains relatively
safe. |
