Nitric oxide and Brazilian propolis combined accelerates tissue repair by modulating cell migration, cytokine production and collagen deposition in experimental leishmaniasis

• Published in: PloS one 2015-05, Vol.10 (5), p.e0125101
• Main Authors: Miranda, Milena Menegazzo, Panis, Carolina, Cataneo, Allan Henrique Depieri, da Silva, Suelen Santos, Kawakami, Natalia Yoshie, Lopes, Luiz Gonzaga de França, Morey, Alexandre Tadachi, Yamauchi, Lucy Megumi, Andrade, Célia Guadalupe Tardelli de Jesus, Cecchini, Rubens, da Silva, Jean Jerley Nogueira, Sforcin, José Maurício, Conchon-Costa, Ivete, Pavanelli, Wander Rogério
• Format: Article
• Language: English
• Subjects: Administration, Oral; Analysis; Animals; Biocompatibility; Care and treatment; Cell migration; Cell Movement - drug effects; Collagen; Collagen - biosynthesis; Combined treatment; Cutaneous leishmaniasis; Cytokines; Cytokines - biosynthesis; Drug Synergism; Drug Therapy, Combination; Drugs; Female; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - parasitology; Fibroblasts - pathology; Health aspects; Hindlimb; Immune response; Immunology; In vivo methods and tests; Inflammation; Injections, Intraperitoneal; Leishmania; Leishmania - drug effects; Leishmania - growth & development; Leishmaniasis; Leishmaniasis, Cutaneous - drug therapy; Leishmaniasis, Cutaneous - parasitology; Leishmaniasis, Cutaneous - pathology; Lesions; Macrophages; Macrophages - drug effects; Macrophages - parasitology; Macrophages - pathology; Mice; Mice, Inbred BALB C; Nitric oxide; Nitric Oxide - pharmacology; Nitric Oxide Donors - chemistry; Nitric Oxide Donors - pharmacology; Parasites; Parasitic diseases; Propolis; Propolis - pharmacology; Rodents; Science; Tegumentary leishmaniasis; Tissue engineering; Vector-borne diseases; Wound healing; Wound Healing - drug effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0125101

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.