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In vivo curative and protective potential of orally administered 5-aminolevulinic acid plus ferrous ion against malaria.

ABSTRACT: 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.

SUBMITTER: Suzuki S

PROVIDER: S-EPMC4604406 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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In vivo curative and protective potential of orally administered 5-aminolevulinic acid plus ferrous ion against malaria.

Suzuki Shigeo S Hikosaka Kenji K Balogun Emmanuel O EO Komatsuya Keisuke K Niikura Mamoru M Kobayashi Fumie F Takahashi Kiwamu K Tanaka Tohru T Nakajima Motowo M Kita Kiyoshi K

Antimicrobial agents and chemotherapy 20150831 11

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 ...[more]

PMID: 26324278

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Project description:Influenza A(H1N1)pdm virus caused the first human pandemic of the 21st century. Although various probiotic Lactobacillus species have been shown to have anti-microbial effects against pneumonia-inducing pathogens, the prophylactic efficacy and mechanisms behind their protection remain largely unknown. Here, we evaluated the prophylactic efficacy of heat-killed Lactobacillus pentosus b240 against lethal influenza A(H1N1)pdm virus infection in a mouse model. To further define the protective responses induced by b240, we performed virologic, histopathologic, and transcriptomic analyses on the mouse lungs. Although we did not observe an appreciable effect of b240 on virus growth, cytokine production, or histopathology, gene expressional analysis revealed that oral administration of b240 differentially regulates antiviral gene expression in mouse lungs. Our results unveil the possible mechanisms behind the protection mediated by b240 against influenza virus infection and provide new insights into probiotic therapy. Six-week-old female BALB/c mice were used in the study. Oral administration of b240 was initiated in mice at six weeks of age. Mice were orally administered heat-killed Lactobacillus pentosus b240 every day at a dose of 10 mg/mouse in 200 Î¼l of buffered saline for 5 weeks. The control group received saline. To investigate the effects of oral administration of b240 on host immune responses to CA04 virus infection, 9 mice per group were infected with 10 MLD50 of CA04 virus on day 21 post-b240 administration. Three mice per group were euthanized on days 1, 3, and 6 post-infection and their lungs were collected. To investigate the immune responses induced by oral administration of b240 in the lungs of uninfected mice, 15 mice per group were mock-infected with PBS on day 21 post-b240 administration. Three mice per group were euthanized on days 14, 21, 22, 24, and 27 post-b240 administration (-7, 0, 1, 3, and 6 days post-mock infection) and their lungs were collected. These lung tissues were subjected to microarray analysis (three biological replicates per each group).

Dataset Information

In vivo curative and protective potential of orally administered 5-aminolevulinic acid plus ferrous ion against malaria.

Publications

In vivo curative and protective potential of orally administered 5-aminolevulinic acid plus ferrous ion against malaria.

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