Anti-leishmanial Effects of Trinitroglycerin in BALB/C Mice Infected with Leishmania major via Nitric Oxide Pathway
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (25)
- Mahmoodi M, "Immune response measured in human volunteers vaccinated with autoclaved Leishmania major vaccine mixed with low dose of BCG", Clin Exp Immunol, 134, pp.303~308 (2003)
- Faryadi M, "Alterations of serum zinc, copper and iron concentrations in patients with acute and chronic cutaneous leishmaniasis", Iranian J Publ Health, 32, pp.53~58 (2003)
- Salih Gurel M, "Cutaneous leishmaniasis in Sanliurfa: epidemiologic and clinical features of the last four years (1997-2000)", Int J Dermatol, 41, pp.32~37 (2002)
- Khalid AF, "In vitro assessment of anti-cutaneous leishmaniasis activity of some sudanese plants", Tu_rkiye Parazitoloji Dergisi, 29, pp.3~6 (2005)
- Nahrevanian H, "Pharmacological evaluation of anti-leishmanial activity by in vivo nitric oxide modulation in BALB", c mice infected with Leishmania major MRHO, 75, pp.ER: an Iranian strain of cutaneous leishmaniasis, Exp Parasitol[DOI]
- Scott PH, "Immunologic memory in cutaneous leishmaniasis", Cell Microbiol, 7, pp.1707~1713 (2005)
- Croft S, "Current scenario of drug development for leishmaniasis", Indian J Med Res, 123, pp.399~410 (2006)
- Holzmuller P, "Nitric oxide-mediated proteasome-dependent oligonucleosomal DNA fragmentation in Leishmania amazonensis amastigotes", Infect Immunol, 70, pp.3727~3735 (2002)
- Stebut E, "Immunology of cutaneous leishmaniasis: the role of mast cells, phagocytes and dendritic cells for protective immunity", Eur J Dermatol, 17, pp.115~122 (2007)
- Spahl UD, "Regulation of zinc homeostasis by inducible NO synthasederived NO: nuclear metallothionein translocation and intranuclear Zn2+ release" (2003), University of California School of Medicine
- Kharazi SH, "The role of overproduction of nitric oxide in apoptosis of BALB", c mice macrophages infected with Leishmania major in vitro, 2003, pp.2, 209~214
- Colassanti M, "Molecular bases for the anti-parasitic effect of NO (review)", Int J Mol Med, 9, pp.131~134 (2002)
- Mossalayi MD, "The human immune response during cutaneous leishmaniasis: no problem", Parasitol Today, 15, pp.342~345 (1999)
- Megson LI, "Nitric oxide donor drugs", Drug Future, 25, pp.701~715 (2000)
- Giudice A, "Resistance of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis to nitric oxide correlates with disease severity in tegumentary leishmaniasis", BMC Infec Dis, 7, pp.7~ (2007)
- Holzmuller P, "Nitric oxide-mediated proteasomedependent oligonucleosomal DNA fragmentation in Leishmania amazonensis amastigotes", Infect Immunol, 70, pp.3727~3735 (2002)
- Erel O, "Reactive nitrogen and oxygen intermediates in patients with cutaneouse leishmaniasis", Mem Inst Osw Cruz, 94, pp.179~183 (1999)
- Nassiri-Kashani M, "A randomized, double-blind, placebo-controlled clinical trial of itraconazole in the treatment of cutaneous leishmaniasis", J Eur Acad Dermatol Venereol, 19, pp.80~83 (2005)
- Kolaczinski J, "Epidemiology of anthroponotic cutaneous leishmaniasis in Afghan refugee camps in North-West Pakistan", Trans R Soc Trop Med Hyg, 98, pp.373~378 (2004)
- Jaafari MR, "Evaluation of leishmanicidal effect of Euphorbia myrsinites extract by in vitro antileishmanial assay using promastigote of Leishmania major", Iranian J Basic Med Sc, 8, pp.295~298 (2005)
- Zeina B, "Topical glycerine trinitrate: a possible treatment for cutaneouse leishmaniasis", Clin Exp Dermatol, 22, pp.244~245 (1997)
- El-On J, "Protection of Guinea pigs against cutaneous leishmaniasis by combined infection and chemotherapy", Infec Immun, 51, pp.704~706 (1986)
- Nahrevanian H, "Nitric oxide and reactive nitrogen intermediates during lethal and non-lethal strains of murine malaria", Parasite Immunol, 23, pp.491~501 (2001)
- Nahrevanian H, "Reactive nitrogen intermediate (RNI) levels inside and outside Plasmodium infected red blood cells in murine malaria", J Trop Med Parasitol, 26, pp.13~19 (2003)
- Nahrevanian H, "Reactive nitrogen intermediate production and tolerance variability in different mouse strains after in vivo treatment with lipopolysaccharide from Salmonella abortus equi", J Microbiol Immunol Infec, 38, pp.164~168 (2005)
