Comment on: S-nitrosoglutathione (GSNO) is cytotoxic to intracellular amastigotes and promotes healing of topically treated Leishmania major or Leishmania braziliensis skin lesions.
Comment on: S-nitrosoglutathione (GSNO) is cytotoxic to intracellular amastigotes and promotes healing of topically treated Leishmania major or Leishmania braziliensis skin lesions.
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评论：S-亚硝基谷胱甘肽 (GSNO) 对细胞内无鞭毛体具有细胞毒性，可促进局部治疗的大型利什曼原虫或巴西利什曼原虫皮肤损伤的愈合。
DOI：
10.1093/jac/dku122
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Olivier Joubert
中科院分区：
文献类型：
--
作者：
C. Ronzani;Ramia Safar;Alain Le Faou;Bertrand H. Rihn;Olivier Joubert
本研究旨在验证S-亚硝基谷胱甘肽（GSNO）对细胞内利什曼原虫无鞭毛体的细胞毒性活性，并测试其作为局部治疗大型利什曼原虫或巴西利什曼原虫感染小鼠局部皮肤利什曼病（LCL）的疗效。方法用L.主要感染的THP-1巨噬细胞。免疫荧光法检测S-亚硝化蛋白。通过每日将GSNO在PBS中的溶液应用于利什曼原虫感染的小鼠的皮肤溃疡来进行局部治疗。BALB/c和IFN-γ-敲除（IFN-γ-KO）C57 BL/6小鼠感染L. major和L. braziliensis，分别。每周测量溃疡大小，并确定病变和淋巴结中的寄生虫负荷。对照组局部接受PBS或静脉内接受阿朴霉素B（AMB）。结果细胞内L.在GSNO处理的培养物中，主要无鞭毛体显著减少;在这些培养物中，S-亚硝化蛋白的染色存在于细胞质中，并与细胞内无鞭毛体共定位。用L. BALB/c小鼠的主要溃疡抑制了损伤生长，减少了寄生虫负荷，并诱导了与静脉内施用AMB的效果相当的愈合。局部GSNO治疗也有效抑制感染L.巴西。结论GSNO对细胞内L.主要无鞭毛体，并对L. major和L.小鼠中的巴西线虫。GSNO对小鼠利什曼病感染的局部治疗作用的这些积极结果为未来可能进行的治疗人类LCL的试验提供了实验基础。
OBJECTIVES This study was designed to verify the cytotoxic activity of S-nitrosoglutathione (GSNO) against intracellular Leishmania amastigotes and to test its efficacy as a topical treatment of localized cutaneous leishmaniasis (LCL) in Leishmania major- or Leishmania braziliensis-infected mice. METHODS Cytotoxic activity of GSNO was verified in L. major-infected THP-1 macrophages. S-nitrosated proteins were detected by immunofluorescence. Topical treatment was done by daily application of a solution of GSNO in PBS to the skin ulcer of Leishmania-infected mice. BALB/c and interferon-γ-knockout (IFN-γ-KO) C57BL/6 mice were infected with L. major and L. braziliensis, respectively. Ulcer size was measured weekly and the parasite loads were determined in the lesion and lymph nodes. Controls received PBS topically or amphotericin B (AMB) intravenously. RESULTS The number of intracellular L. major amastigotes was markedly reduced in GSNO-treated cultures; in these, staining for S-nitrosated proteins was present in the cytoplasm and colocalized with intracellular amastigotes. Topical treatment with GSNO of L. major ulcers in BALB/c mice suppressed lesion growth, reduced the parasite load and induced healing comparable to the effect of intravenously administered AMB. Topical GSNO treatment was also efficient at suppressing lesion growth in IFN-γ-KO mice infected with L. braziliensis. CONCLUSIONS GSNO is cytotoxic to intracellular L. major amastigotes in vitro and had a healing effect on LCL caused by L. major and L. braziliensis in mice. These positive results on the topical therapeutic effect of GSNO in mouse leishmaniasis infections provide the experimental basis for a possible future trial in the treatment of human LCL.
影响因子：
6.6
作者：
Kim, Jinsu;Won, Je-Seong;Singh, Inderjit
通讯作者：
Singh, Inderjit
影响因子：
3
作者：
Tang, Chi-Hui;Wei, Wei;Liu, Limin
通讯作者：
Liu, Limin
DOI：
10.1016/j.bbrc.2005.08.150
发表时间：
2005-10-21
影响因子：
3.1
作者：
Hongo, F;Garban, H;Bonavida, B
通讯作者：
Bonavida, B