title: Nerve growth factor promotes killing of Leishmania donovani by macrophages through the induction of hydrogen peroxide.
abstract: Visceral leishmaniasis is protozoonosis that occurs worldwide and still requires effective therapies with less toxicity. In this study, we examined the antileishmanial effect of nerve growth factor (NGF) using a murine infection model. NGF blocked the infection of macrophages by Leishmania donovani, which was completely cancelled by a hydrogen peroxide inhibitor. In vivo, not only did NGF show antileishmanial effects, but combination therapy of NGF and sodium stibogluconate synergistically exhibited the activity more potently than each monotherapy. These results indicate that NGF exerts antileishmanial effect by stimulating hydrogen peroxide production in macrophages and can be a novel therapy for leishmaniasis.
authors.affiliation: Laboratories of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life Science, Tokyo University of Agriculture and Technology, 3-5-8, Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Chiba
authors.affiliation: Laboratories of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life Science, Tokyo University of Agriculture and Technology, 3-5-8, Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Amagai
authors.affiliation: Laboratories of Comparative Animal Medicine, Division of Animal Life Science, Tokyo University of Agriculture and Technology, 3-5-8, Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Laboratory of Parasitology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Katakura
authors.affiliation: Laboratories of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life Science, Tokyo University of Agriculture and Technology, 3-5-8, Saiwai-cho, Fuchu, Tokyo 183-8509, Japan. Electronic address: hiro@cc.tuat.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology*; D008807:Mice, Inbred BALB C; D020932:Nerve Growth Factor / Q000276:immunology* / Q000378:metabolism* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D020932:Nerve Growth Factor; D006861:Hydrogen Peroxide; D000967:Antimony Sodium Gluconate
keywords: Leishmania; Macrophages; Nerve growth factor; Peroxide