Topical glyceryl trinitrate: a possible treatment for cutaneous leishmaniasis

Zeina, B.; Banfield, Cedric C.; Al-Assad, Saada

doi:10.1111/j.1365-2230.1997.tb01079.x

Cited by 20 publications

(6 citation statements)

References 5 publications

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“…29 Indeed, survival of Leishmania within host macrophages depends on the parasite's ability to inhibit host iNOS expression or activity. 48 Zeina et al 49 successfully treated a male patient with cutaneous leishmaniasis with topical glyceryl trinitrate, an exogenous NO donor. The S-nitrosoglutathione (GSNO), S-nitroso-Nacetyl-l-cysteine (SNAC), 48 and peroxynitrite 50 have demonstrated leishmanicidal activity in vitro.…”

Section: Parasitesmentioning

confidence: 99%

Use of nitric oxide nanoparticulate platform for the treatment of skin and soft tissue infections

Kutner

Friedman

2013

WIREs Nanomed Nanobiotechnol

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The incidence of skin and soft tissue infections (SSTI) due to multi-drug resistant pathogens is increasing. The concomitant increase in antibiotic use along with the ease with which organisms develop mechanisms of resistance have together become a medical crisis, underscoring the importance of developing innovative and effective antimicrobial strategies. Nitric oxide (NO) is an endogenously produced molecule with many physiologic functions, including broad spectrum antimicrobial activity and immunomodulatory properties. The risk of resistance to NO is minimized because NO has multiple mechanisms of antimicrobial action. NO's clinical utility has been limited largely because it is highly reactive and lacks appropriate vehicles for storage and delivery. To harness NO's antimicrobial potential, a variety exogenous NO delivery platforms have been developed and evaluated, yet limitations preclude their use in the clinical setting. Nanotechnology represents a paradigm through which these limitations can be overcome, allowing for the encapsulation, controlled release, and focused delivery of NO for the treatment of SSTI.

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Section: Parasitesmentioning

confidence: 99%

Use of nitric oxide nanoparticulate platform for the treatment of skin and soft tissue infections

Kutner

Friedman

2013

WIREs Nanomed Nanobiotechnol

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“…Notably, NO and related reactive nitrogen intermediates released from NO-donors kill T. cruzi, L. infantum and P. falciparum [39,[41][42][43]. Moreover, the NO-donor glyceryl trinitrate has been reported to be effective in the treatment of cutaneous leishmaniasis in man [44][45][46].…”

Section: Parasite Cysteine Proteasesmentioning

confidence: 99%

Inhibition of Cysteine Protease Activity by NO-donors

Ascenzi¹,

Salvati²,

Bolognesi³

et al. 2001

CPPS

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Cysteine proteases represent a broad class of proteolytic enzymes widely distributed among living organisms. Although well known as typical lysosomal enzymes, cysteine proteases are actually recognized as multi-function enzymes, being involved in antigen processing and presentation, in membrane-bound protein cleavage, as well as in degradation of the cellular matrix and in processes of tissue remodeling. Very recently, it has been shown that the NO(-donor)-mediated chemical modification of the Cys catalytic residue of cysteine proteases, including Coxsackievirus and Rhinovirus cysteine proteases, cruzain, Leishmania infantum cysteine protease, falcipain, papain, as well as mammalian caspases, cathepsins and calpain, blocks the enzyme activity in vitro and in vivo. Here, inhibition of representative cysteine proteases by NO(-donors) is reviewed.

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“…Trinitroglycerin (TNG) was the first to be described as antianginal drug, and it is still used in the treatment of heart failure [8], which is known to be an exogenous donor of NO [21]. TNG is a substance that is metabolized to NO in the cells and its action is not dependent on the endothelium derived NO and may inhibit the catalytic activity of Leishmania [14].…”

Section: Introductionmentioning

confidence: 99%

“…TNG is a substance that is metabolized to NO in the cells and its action is not dependent on the endothelium derived NO and may inhibit the catalytic activity of Leishmania [14]. Since, TNG has been used safely for over a century to treat medical conditions [21], this investigation was carried out to clarify whether TNG as NOreleasing agent had anti-leishmanial effects and mediated pathology in mice infected with L. major in vivo.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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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.

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Topical glyceryl trinitrate: a possible treatment for cutaneous leishmaniasis

Cited by 20 publications

References 5 publications

Use of nitric oxide nanoparticulate platform for the treatment of skin and soft tissue infections

Use of nitric oxide nanoparticulate platform for the treatment of skin and soft tissue infections

Inhibition of Cysteine Protease Activity by NO-donors

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

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