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In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria

5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that th...

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Autores principales: Suzuki, Shigeo, Hikosaka, Kenji, Balogun, Emmanuel O., Komatsuya, Keisuke, Niikura, Mamoru, Kobayashi, Fumie, Takahashi, Kiwamu, Tanaka, Tohru, Nakajima, Motowo, Kita, Kiyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604406/
https://www.ncbi.nlm.nih.gov/pubmed/26324278
http://dx.doi.org/10.1128/AAC.01910-15
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author Suzuki, Shigeo
Hikosaka, Kenji
Balogun, Emmanuel O.
Komatsuya, Keisuke
Niikura, Mamoru
Kobayashi, Fumie
Takahashi, Kiwamu
Tanaka, Tohru
Nakajima, Motowo
Kita, Kiyoshi
author_facet Suzuki, Shigeo
Hikosaka, Kenji
Balogun, Emmanuel O.
Komatsuya, Keisuke
Niikura, Mamoru
Kobayashi, Fumie
Takahashi, Kiwamu
Tanaka, Tohru
Nakajima, Motowo
Kita, Kiyoshi
author_sort Suzuki, Shigeo
collection PubMed
description 5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe(2+)) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug.
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spelling pubmed-46044062015-11-16 In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria Suzuki, Shigeo Hikosaka, Kenji Balogun, Emmanuel O. Komatsuya, Keisuke Niikura, Mamoru Kobayashi, Fumie Takahashi, Kiwamu Tanaka, Tohru Nakajima, Motowo Kita, Kiyoshi Antimicrob Agents Chemother Experimental Therapeutics 5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe(2+)) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug. American Society for Microbiology 2015-10-13 2015-11 /pmc/articles/PMC4604406/ /pubmed/26324278 http://dx.doi.org/10.1128/AAC.01910-15 Text en Copyright © 2015, Suzuki et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Experimental Therapeutics
Suzuki, Shigeo
Hikosaka, Kenji
Balogun, Emmanuel O.
Komatsuya, Keisuke
Niikura, Mamoru
Kobayashi, Fumie
Takahashi, Kiwamu
Tanaka, Tohru
Nakajima, Motowo
Kita, Kiyoshi
In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria
title In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria
title_full In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria
title_fullStr In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria
title_full_unstemmed In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria
title_short In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria
title_sort in vivo curative and protective potential of orally administered 5-aminolevulinic acid plus ferrous ion against malaria
topic Experimental Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604406/
https://www.ncbi.nlm.nih.gov/pubmed/26324278
http://dx.doi.org/10.1128/AAC.01910-15
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