Abstract:
Immune metabolic adaptation in macrophages by intracellular parasites is recognized to
play a crucial role during Leishmania infection. However, there is little accessible
information about changes in a metabolic switch in L. donovani infected macrophages.
In previous studies, we have reported on the anti-leishmanial synergic effect of eugenol
oleate with amphotericin B. In the present study, we demonstrated that glycolytic
enzymes were highly expressed in infected macrophages during combinatorial
treatment of eugenol oleate (2.5 μM) and amphotericin B (0.3125 μM). Additionally, we
found that the biphasic role in arachidonic acid metabolite, PGE2, and LTB4, is released
during this treatment. In vitro data showed that COX-2 mediated PGE2 synthesis
increased significantly (p<0.01) in infected macrophages. Not only was the level of
prostaglandin synthesis decreased 4.38 fold in infected macrophages after treatment
with eugenol oleate with amphotericin B. The mRNA expression of PTGES, MPGES, and
PTGER4 were also moderately expressed in infected macrophages, and found to be
decreased in combinatorial treatment. In addition, NOS2 expression was activated by the
phosphorylation of p38MAPK when combination-treated macrophages were promoted
to kill intracellular parasites. The findings of the present study indicate that the synergism
between eugenol oleate and amphotericin B could play an important role in immune
metabolism adaptation with a concomitant increase in host immune response against the
intracellular pathogen, L. donovani.
