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. |