M Jesús Corral1, Dolores R Serrano2, Inmaculada Moreno3, J J Torrado2, Mercedes Domínguez3, José M Alunda4. 1. Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain. 2. Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain. 3. Unidad de Inmunología Microbiana, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. 4. Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain jmalunda@ucm.es.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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.
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Authors: Jéssica A Jesus; Thais N Fragoso; Eduardo S Yamamoto; Márcia D Laurenti; Marcelo S Silva; Aurea F Ferreira; João Henrique G Lago; Gabriela Santos-Gomes; Luiz Felipe D Passero Journal: Int J Parasitol Drugs Drug Resist Date: 2016-12-08 Impact factor: 4.077
Authors: A I Olías-Molero; I Moreno; M J Corral; M D Jiménez-Antón; M J Day; M Domínguez; J M Alunda Journal: Sci Rep Date: 2020-11-02 Impact factor: 4.379
Authors: María J Corral; Elena Benito-Peña; M Dolores Jiménez-Antón; Laureano Cuevas; María C Moreno-Bondi; José M Alunda Journal: PLoS Negl Trop Dis Date: 2016-03-29
Authors: Elisangela Oliveira Freitas; Dirlei Nico; Marcus Vinícius Alves-Silva; Alexandre Morrot; Keith Clinch; Gary B Evans; Peter C Tyler; Vern L Schramm; Clarisa B Palatnik-de-Sousa Journal: PLoS Negl Trop Dis Date: 2015-12-23