Anti-leishmanial Effects of Trinitroglycerin in BALB/C Mice Infected with Leishmania major via Nitric Oxide Pathway

Abstract

This study investigated whether trinitroglycerine (TNG) as nitric oxide (NO) releasing agent had anti-leishmanial effects and mediated pathology in BALB/c mice infected with Leishmania major. Cutaneous leishmaniasis (CL), a zoonotic infection caused by leishmania protozoa is still one of the health problems in the world and in Iran. NO is involved in host immune responses against intracellular L. major, and leishmania killing by macrophages is mediated by this substance. Moreover, application of CL treatment with NO-donors has been recently indicated. In our study, TNG was used for its ability to increase NO and to modify CL infection in mice, in order to evaluate NO effects on lesion size and formation, parasite proliferation inside macrophages, amastigote visceralization in target organs, and NO induction in plasma and organ suspensions. Data obtained in this study indicated that TNG increased plasma and liver-NO, reduced lesion sizes, removed amastigotes from lesions, livers, spleens, and lymph nodes, declined proliferation of amastigotes, hepatomegaly, and increased survival rate. However, TNG reduced spleen-NO and had no significant effects on spelenomegaly. The results show that TNG therapy reduced leishmaniasis and pathology in association with raised NO levels. TNG had some antiparasitic activity by reduction of positive smears from lesions, livers, spleens, and lymph nodes, which could emphasize the role of TNG to inhibit visceralization of L. major in target organs.

Nitric oxide contributes to learning and memory deficits observed in hypothyroid rats during neonatal and juvenile growth

“…The contents were then vortex-mixed and centrifuged, and the supernatants were transferred to a 96-well flat-bottomed microplate. Absorbance was read at 520 nm using a microplate reader, and final values were calculated from standard calibration plots 36. …”

Immunomodulation by chemotherapeutic agents against Leishmaniasis

“…a mononuclear diperoxovanadate compound K[VO(O 2 ) 2 (H 2 O)]PV6 [44]. Similarly, an ethanolic extract of Tinospora sinensis [45], 18 Beta-glycyrrhetinic acid [46], tannins and related compounds [47], trinitroglycerin [48] also upregulated production of NO (Table 2). Interestingly, Cystatin along with IFN-γ, induced generation of NO but markedly reduced expression of iNOS at both mRNA and protein levels [49][50][51].…”

Is topical nitric oxide and cryotherapy more effective than cryotherapy in the treatment of old world cutaneous leishmaniasis?

“…The leishmanicidal effect of NO seemed to be the consequence of induction of a programmed cell death-like process. However, both in vitro and in vivo immunological studies indicate that NO radicals within Leishmania lesions could reduce the parasite number (15).…”