title: Efficacy of low doses of amphotericin B plus allicin against experimental visceral leishmaniasis.
abstract: OBJECTIVE
  To evaluate the efficacy of the combination of allicin and amphotericin deoxycholate (AmB) in the chemotherapy of Leishmania infantum infection with the final aim of reducing the dose of AmB in the chemotherapy of visceral leishmaniasis.
  
  
  METHODS
  Hamsters were intraperitoneally (ip) infected with L. infantum (10(7) stationary phase promastigotes). On day 45 post-infection animals were treated ip with AmB (1 or 5 mg/kg/day), allicin (5 mg/kg/day) or a combination of AmB (1 mg/kg/day) + allicin (5 mg/kg/day) for 5 days. Animals were clinically and biopathologically monitored and the antibody response (IgG, IgG1, IgG2) was determined. Parasite burdens were estimated by limiting dilution and AmB biodistribution was determined by HPLC in plasma, kidney, spleen and liver.
  
  
  RESULTS
  No clinical signs or liver and kidney alterations were observed. AmB (1 mg/kg/day) did not clear the Leishmania infection and no parasites were detected in two animals treated with 5 mg/kg/day allicin. Combination therapy (5 mg/kg allicin + 1 mg/kg AmB) reduced the L. infantum burden by >95%. Antileishmanial activity of the combination was comparable (P < 0.05) to the standard AmB treatment (5 mg/kg).
  
  
  CONCLUSIONS
  Allicin alone (5 mg/kg/day for 5 days) significantly reduced the Leishmania burden in spleen and liver of infected hamsters. Co-administration of allicin (5 mg/kg/day for 5 days) and AmB (1 mg/kg/day for 5 days) showed a partial additive effect on the reduction of leishmanial burden in both target organs.
authors.affiliation: Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Corral
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Dolores R
authors.initials: DR
authors.lastname: Serrano
authors.affiliation: Unidad de Inmunología Microbiana, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Moreno
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Torrado
authors.affiliation: Unidad de Inmunología Microbiana, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Domínguez
authors.affiliation: Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain jmalunda@ucm.es.
authors.forename: José M
authors.initials: JM
authors.lastname: Alunda
mesh_terms: D000666:Amphotericin B / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000825:Animal Structures / Q000737:chemistry; D000818:Animals; D000981:Antiprotozoal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004195:Disease Models, Animal; D004220:Disulfides; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D018314:Leishmania infantum / Q000187:drug effects* / Q000302:isolation & purification; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D059208:Parasite Load; D010949:Plasma / Q000737:chemistry; D013441:Sulfinic Acids / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D004220:Disulfides; D013441:Sulfinic Acids; C006452:allicin; D000666:Amphotericin B
keywords: Leishmania; allicin; amphotericin; hamster; visceral leishmaniasis