Background: Schistosomiasis is a
major public health problem in developing
countries. Currently, praziquantel
(PZQ) is the drug of choice
for
human schistosomiasis. Isosorbide-5-mononitrate
(IS-5-MN) is a nitro
compound that is used as an antianginal
remedy. It must be
enzymatically
metabolized to release
nitric
oxide (NO) to exert its pharmacologic
activities. This study evaluates
the vasodilator effect of the
NO
donor IS-5-MN on hepatic bilharzial
lesions caused by Schistosoma
mansoni,
and determines whether
the
combined use of IS-5-MN and
PZQ
is synergistic or antagonistic. Methods: Swiss albino female
mice (CD I strain) were divided into
five groups: (i) non-infected; (ii) infected
non-treated; (iii) infected and
treated
with PZQ, 6 weeks post infection
(WPI) in a dose of 500 mg/
kg/day
for two successive days; (iv)
infected
and treated with IS-5-MN
from
the fourth to the tength WPI 5
days/week
in a dose of 10.08 mg/kg;
(v)
infected and treated with IS-5-MN
as
group (iv) in addition to PZQ as
group < br />(iii). Parasitological, biochemical
and histopathological parameters
that
assess disease severity and
morbidity
were investigated.
Results: PZQ significantly in- creased the percentage of dead
eggs, decreased granuloma number
but did not reduce granuloma diameter.
IS-5-MN administered alone did
not
induce a shift in the oogram pattern,
but it reduced inflammation, necrosis
and granuloma diameter. The
simultaneous
administration of both
drugs
significantly increased NO level
in liver homogenates and induced
modulation
of granuloma size. The
best
results were obtained in the
mice
group treated with IS-5-MN in
addition
to PZQ.
Conclusions: Our results point to
IS-5-MN as a promising medication
that could be used as a combined
therapy with PZQ to ameliorate
schistosomal liver pathology. Further
studies are recommended to explore
effects of IS-5-MN and PZQ coadministration
in schistosomiasis advanced
liver fibrosis.