Previous studies have shown that carbaporphyrin ketals (CK) induce the formation of reactive oxygen species (ROS) in Leishmania tarentolae (Morgenthaler et al. 2008). Using the nitric oxide synthase (NOS) inhibitor, N?-nitro-L-arginine, this study tested the effects of inhibiting L. tarentolae NOS, thereby reducing the ability of the parasite to produce nitric oxide (NO). The hypothesis was that NO is produced as a defense mechanism by the cells in the presence of CK. Solutions of inhibitor or CK in dimethyl sulfoxide (DMSO) were used. Leishmania promastigotes were cultured in brain heart infusion (BHI) growth medium, at room temperature, in sterile flasks. Cells were incubated with various concentrations of CK with or without inhibitor and assessed for cell viability. Control cells were incubated with DMSO only. Cell viability was monitored using an MTT assay in 96-well plates. At 3 �M or 5 �M CK, cultures without inhibitor exhibited 100% cell death compared to control cells. At 3 �M and 5 �M, cultures with NOS inhibitor showed a 47% and 93% reduction in cell viability, respectively. Thus, it appears that inhibiting the ability of cells to produce NO results in greater cell viability when exposed to CK. The data suggest a complex interaction of de novo NO with reactive oxygen species in the parasite. Further studies will include monitoring the concentration dependent effectiveness of the inhibitor and mechanism of CK interaction with NO using electron paramagnetic resonance (EPR) spectroscopy.

Progress in the inhibition of <i>Leishmania tarentolae</i> nitric oxide synthase (NOS) in the presence of carbaporphyrin ketals

246th National Meeting (2013)

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Progress in the inhibition of Leishmania tarentolae nitric oxide synthase (NOS) in the presence of carbaporphyrin ketals