title: Prophylactic or therapeutic administration of Agaricus blazei Murill is effective in treatment of murine visceral leishmaniasis.
abstract: The present study aimed to investigate the in vitro antileishmanial activity of five fractions obtained from Agaricus blazei water extract (AbM), namely, Fab1, Fab2, Fab3, Fab4, and Fab5; and use the selected leishmanicidal fraction to treat BALB/c mice infected with Leishmania chagasi. A curve dose-titration was performed to obtain the concentration to be test in infected animals. In this context, Fab5 fraction and AbM were used in the doses of 20 and 100 mg/kg/day, respectively, with the product been administered once a day. The effect induced by a chemo-prophylactic regimen, based on the administration Fab5 fraction and AbM 5 days before infection, and maintained for an additional 20 days post-infection was compared to a therapeutic regimen, in which the compounds were administered from 0 to 20 days of infection. Control animals were either treated with amphotericin B deoxycholate (AmpB) or received distilled water. All groups were followed up for 10 weeks post-infection, when parasitological and immunological parameters were analyzed. The Fab5 presented the best results of in vitro leishmanicidal activity. In the in vivo experiments, the use of Fab5 or AbM, as compared to control groups, resulted in significant reduced parasite burdens in the liver, spleen, and draining lymph nodes of the infected animals, as compared to control groups. A Type 1 immune response was observed in the Fab5 or AbM treated animals. No significant toxicity was observed. The chemo-prophylactic regimen proved to be more effective to induce theses responses. In this context, the data presented in this study showed the potential of the purified Fab5 fraction of AbM as a therapeutic alternative to treat visceral leishmaniasis. In addition, it can be postulated that this fraction can be also employed in a chemo-prophylactic regimen associated or not with other therapeutic products.
authors: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31.270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Diogo G
authors: DG
authors: Valadares
authors: Mariana C
authors: MC
authors: Duarte
authors: Laura
authors: L
authors: Ramírez
authors: Miguel A
authors: MA
authors: Chávez-Fumagalli
authors: Vivian T
authors: VT
authors: Martins
authors: Lourena E
authors: LE
authors: Costa
authors: Paula S
authors: PS
authors: Lage
authors: Tatiana G
authors: TG
authors: Ribeiro
authors: Rachel O
authors: RO
authors: Castilho
authors: Ana Paula
authors: AP
authors: Fernandes
authors: Wiliam C B
authors: WC
authors: Régis
authors: Manuel
authors: M
authors: Soto
authors: Carlos A P
authors: CA
authors: Tavares
authors: Eduardo A F
authors: EA
authors: Coelho
mesh_terms: D000364:Agaricus / Q000737:chemistry*; D000818:Animals; D000981:Antiprotozoal Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D020128:Inhibitory Concentration 50; D018314:Leishmania infantum / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000517:prevention & control; D008099:Liver / Q000469:parasitology; D008198:Lymph Nodes / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000469:parasitology
chemical_list: D000981:Antiprotozoal Agents; D016207:Cytokines