Efficacy of low doses of amphotericin B plus allicin against experimental visceral leishmaniasis

• Published in: Journal of antimicrobial chemotherapy 2014-12, Vol.69 (12), p.3268-3274
• Main Authors: Corral, M Jesús, Serrano, Dolores R, Moreno, Inmaculada, Torrado, J J, Domínguez, Mercedes, Alunda, José M
• Format: Article
• Language: English
• Subjects: Amphotericin B - pharmacokinetics; Amphotericin B - therapeutic use; Animal Structures - chemistry; Animals; Antiprotozoal Agents - pharmacokinetics; Antiprotozoal Agents - therapeutic use; Chemotherapy; Chromatography, High Pressure Liquid; Cricetinae; Disease Models, Animal; Drug Therapy, Combination - methods; Female; Immunoglobulins; Leishmania infantum; Leishmania infantum - drug effects; Leishmania infantum - isolation & purification; Leishmaniasis, Visceral - drug therapy; Medical treatment; Parasite Load; Parasites; Plasma - chemistry; Rodents; Sulfinic Acids - pharmacokinetics; Sulfinic Acids - therapeutic use; Treatment Outcome
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dku290

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. 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. 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). 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.