title: Nitric oxide and Brazilian propolis combined accelerates tissue repair by modulating cell migration, cytokine production and collagen deposition in experimental leishmaniasis.
abstract: The fact that drugs currently used in the treatment of Leishmania are highly toxic and associated with acquired resistance has promoted the search for new therapies for treating American tegumentary leishmaniasis (ATL). In this study, BALB/c mice were injected in the hind paw with Leishmania (Leishmania) amazonensis and subsequently treated with a combination of nitric oxide (NO) donor (cis-[Ru(bpy) 2imN(NO)](PF6)3) (Ru-NO), given by intraperitoneal injection, and oral Brazilian propolis for 30 days. Ru-NO reached the center of the lesion and increased the NO level in the injured hind paw without lesion exacerbation. Histological and immunological parameters of chronic inflammation showed that this combined treatment increased the efficacy of macrophages, determined by the decrease in the number of parasitized cells, leading to reduced expression of proinflammatory and tissue damage markers. In addition, these drugs in combination fostered wound healing, enhanced the number of fibroblasts, pro-healing cytokines and induced collagen synthesis at the lesion site. Overall, our findings suggest that the combination of the NO donor Ru-NO and Brazilian propolis alleviates experimental ATL lesions, highlighting a new therapeutic option that can be considered for further in vivo investigations as a candidate for the treatment of cutaneous leishmaniasis.
authors.affiliation: Department of Pathology Science, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.
authors.forename: Milena Menegazzo
authors.initials: MM
authors.lastname: Miranda
authors.affiliation: Laboratory of Inflammatory Mediators, State University of Western Paraná, Francisco Beltrão, Paraná, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Panis
authors.affiliation: Department of Pathology Science, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.
authors.forename: Allan Henrique Depieri
authors.initials: AH
authors.lastname: Cataneo
authors.affiliation: Department of Pathology Science, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.
authors.forename: Suelen Santos
authors.initials: SS
authors.lastname: da Silva
authors.affiliation: Department of Pathology Science, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.
authors.forename: Natalia Yoshie
authors.initials: NY
authors.lastname: Kawakami
authors.affiliation: Department of Organic and Inorganic Chemistry, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Luiz Gonzaga de França
authors.initials: LG
authors.lastname: Lopes
authors.affiliation: Department of Microbiology, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.
authors.forename: Alexandre Tadachi
authors.initials: AT
authors.lastname: Morey
authors.affiliation: Department of Microbiology, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.
authors.forename: Lucy Megumi
authors.initials: LM
authors.lastname: Yamauchi
authors.affiliation: Laboratory of Electron Microscopy and Microanalysis, Department of General Biology, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.
authors.forename: Célia Guadalupe Tardelli de Jesus
authors.initials: CG
authors.lastname: Andrade
authors.affiliation: Department of Pathology Science, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.
authors.forename: Rubens
authors.initials: R
authors.lastname: Cecchini
authors.affiliation: Department of Chemistry, State University of Roraima, Boa Vista, Roraima, Brazil.
authors.forename: Jean Jerley Nogueira
authors.initials: JJ
authors.lastname: da Silva
authors.affiliation: Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University, Botucatu, São Paulo, Brazil.
authors.forename: José Maurício
authors.initials: JM
authors.lastname: Sforcin
authors.affiliation: Department of Pathology Science, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.
authors.forename: Ivete
authors.initials: I
authors.lastname: Conchon-Costa
authors.affiliation: Department of Pathology Science, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.
authors.forename: Wander Rogério
authors.initials: WR
authors.lastname: Pavanelli
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000469:parasitology / Q000473:pathology; D006614:Hindlimb; D007274:Injections, Intraperitoneal; D007891:Leishmania / Q000187:drug effects* / Q000254:growth & development; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000737:chemistry* / Q000494:pharmacology; D011429:Propolis / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D016207:Cytokines; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D003094:Collagen; D011429:Propolis