Serum and tissue nitrate levels in murine visceral leishmaniasis correlate with parasite load but not with host protection

Nitrate levels were measured in serum and in organs from Lsh5 BALB/c and Lshr C3H/HeN mice during the acute phase (30 d) of infection by Leishmania donovani strain LV9. Serum nitrate levels increased rapidly in balb/c mice from a baseline level (17 ± 4 μmol/L) to a plateau (504 ± 129 μmol/L) at 24 d and correlated with parasite loads in the liver (r = 0 · 817, P < 0 · 01) and in the spleen (r = 0 · 854, P < 0 · 001). Liver and spleen nitrate contents were enhanced 2 · 7-fold and 22 · 8-fold, respectively, with respect to uninfected controls (2692 ± 249 vs. 992 ± 231 nmol, P < 0 · 02 and 20 ± 1 vs. 456 ± 43 nmol, P < 0 · 02). In contrast, serum nitrate increased to a lesser extent in C3H/HeN mice, from 31 ± 5 μmol/L to 86 ± 5 μmol/L at 20 d. Liver nitrate content did not differ significantly between infected and control mice (1093 + 83 vs. 867 ± 104 nmol), whereas the former had a higher spleen nitrate content (145 ± 22 vs. 40±2 nmol, P < 0 · 02). Our findings indicate that production of NO by the susceptible BALB/c strain exceeded that of the resistant C3H/HeN strain during the acute stage of infection by L. donovani. Tissue NO overproduction in organs infected by L. donovani was related to the progression of parasitic disease and contributed to high nitrate serum levels. It would be very interesting to extend this investigation to human disease with the aim of evaluating serum nitrate as a marker of parasite load in the follow-up of patients suffering from visceral leishmaniasis.