title: DETC-based bacterial cellulose bio-curatives for topical treatment of cutaneous leishmaniasis.
abstract: The treatment of leishmaniasis still relies on drugs with potentially serious adverse effects. Herein, we tested a topical formulation of bacterial cellulose (BC) membranes containing Diethyldithiocarbamate (DETC), a superoxide dismutase 1 inhibitor. Leishmania-infected macrophages exposed to BC-DETC resulted in parasite killing, without pronounced toxic effects to host cells. This outcome was associated with lower SOD1 activity and higher production of superoxide and cytokine mediators. Topical application of BC-DETC significantly decreased lesion size, parasite load and the inflammatory response at the infection site, as well as the production of both IFN-γ and TNF. Combination of topical BC-DETC plus intraperitoneal Sbvalso significantly reduced disease development and parasite load. The leishmanicidal effect of BC-DETC was extended to human macrophages infected with L. braziliensis, highlighting the feasibility of BC-DETC as a topical formulation for chemotherapy of cutaneous leishmaniasis caused by L. braziliensis.
authors.affiliation: Instituto Gonçalo Moniz, FIOCRUZ, Salvador, BA, Brazil.
authors.forename: Fabiana S
authors.initials: FS
authors.lastname: Celes
authors.affiliation: Instituto de Química, Universidade Estadual Paulista, Araraquara, SP, Brazil.|Universidade de Araraquara-UNIARA, Araraquara, SP, Brazil.
authors.forename: Eliane
authors.initials: E
authors.lastname: Trovatti
authors.affiliation: Instituto Gonçalo Moniz, FIOCRUZ, Salvador, BA, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Khouri
authors.affiliation: Rega Institute for Medical Research, Department of Microbiology and Immunology, K. U. Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Van Weyenbergh
authors.affiliation: Instituto de Química, Universidade Estadual Paulista, Araraquara, SP, Brazil.
authors.forename: Sidney J L
authors.initials: SJ
authors.lastname: Ribeiro
authors.affiliation: Instituto Gonçalo Moniz, FIOCRUZ, Salvador, BA, Brazil.
authors.forename: Valeria M
authors.initials: VM
authors.lastname: Borges
authors.affiliation: Instituto de Química, Universidade Estadual Paulista, Araraquara, SP, Brazil.|Universidade de Araraquara-UNIARA, Araraquara, SP, Brazil.
authors.forename: Hernane S
authors.initials: HS
authors.lastname: Barud
authors.affiliation: Instituto Gonçalo Moniz, FIOCRUZ, Salvador, BA, Brazil.|Instituto de Investigação em Imunologia (iii), INCT, São Paulo, Brazil.
authors.forename: Camila I
authors.initials: CI
authors.lastname: de Oliveira
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D002482:Cellulose / Q000737:chemistry* / Q000302:isolation & purification; D016207:Cytokines / Q000096:biosynthesis; D004050:Ditiocarb / Q000737:chemistry / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005260:Female; D041821:Gluconacetobacter / Q000737:chemistry; D006801:Humans; D007274:Injections, Intraperitoneal; D007892:Leishmania braziliensis / Q000187:drug effects* / Q000254:growth & development; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000378:metabolism / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D008536:Meglumine / Q000494:pharmacology*; D000077485:Meglumine Antimoniate; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000494:pharmacology*; D061251:Primary Cell Culture; D000072105:Superoxide Dismutase-1 / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D016207:Cytokines; D009942:Organometallic Compounds; D013481:Superoxides; D008536:Meglumine; D000077485:Meglumine Antimoniate; D002482:Cellulose; D004050:Ditiocarb; D000072105:Superoxide Dismutase-1