Reduction of Sb(V) in a Human Macrophage Cell Line Measured by HPLC-ICP-MS

Hansen, Claus; Hansen, Erik W.; Hansen, Hanna E.; Gammelgaard, Bente; Stürup, Stefan

doi:10.1007/s12011-011-9079-9

Cited by 30 publications

(20 citation statements)

References 25 publications

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“…Reduction of the pro-drug Sb V to the bioactive Sb III has been shown to occur both in Leishmania amastigotes and host cells, but not promastigotes [10, 39, 40]. Thus, alterations in host cell drug uptake and metabolism could directly impact exposure of the intracellular parasite to the drug, parasite survival and the efficacy of treatments.…”

Section: Discussionmentioning

confidence: 99%

Profiling gene expression of antimony response genes in Leishmania (Viannia) panamensis and infected macrophages and its relationship with drug susceptibility

et al. 2017

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The mechanisms of Leishmania resistance to antimonials have been primarily determined in experimentally derived Leishmania strains. However, their participation in the susceptibility phenotype in field isolates has not been conclusively established. Being an intracellular parasite, the activity of antileishmanials is dependent on internalization of drugs into host cells and effective delivery to the intracellular compartments inhabited by the parasite. In this study we quantified and comparatively analyzed the gene expression of nine molecules involved in mechanisms of xenobiotic detoxification and Leishmania resistance to antimonial drugs in resistant and susceptible laboratory derived and clinical L.(Viannia) panamensis strains (n=19). In addition, we explored the impact of Leishmania susceptibility to antimonials on the expression of macrophage gene products having putative functions in transport, accumulation and metabolism of antimonials. As previously shown for other Leishmania species, a trend of increased abcc3 and lower aqp-1 expression was observed in the laboratory derived Sb-resistant L.(V.) panamensis line. However, this was not found in clinical strains, in which the expression of abca2 was significantly higher in resistant strains as both, promastigotes and intracellular amastigotes. The effect of drug susceptibility on host cell gene expression was evaluated on primary human macrophages from patients with cutaneous leishmaniasis (n=17) infected ex-vivo with the matched L.(V.) panamensis strains isolated at diagnosis, and in THP-1 cells infected with clinical strains (n=6) and laboratory adapted L.(V.) panamensis lines. Four molecules, abcb1 (p-gp), abcb6, aqp-9 and mt2a were differentially modulated by drug resistant and susceptible parasites, and among these, a consistent and significantly increased expression of the xenobiotic scavenging molecule mt2a was observed in macrophages infected with Sb-susceptible L. (V.) panamensis. Our results substantiate that different mechanisms of drug resistance operate in laboratory adapted and clinical Leishmania strains, and provide evidence that parasite-mediated modulation of host cell gene expression of molecules involved in drug transport and metabolism could contribute to the mechanisms of drug resistance and susceptibility in Leishmania.

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Section: Discussionmentioning

confidence: 99%

Profiling gene expression of antimony response genes in Leishmania (Viannia) panamensis and infected macrophages and its relationship with drug susceptibility

et al. 2017

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“…A marine macroalga, Sargassum sp., was the first reported organism able to reduce Sb(V) in seawater (59). In the treatment of leishmaniasis, several studies suggested that Sb(V), when used as a prodrug medicine, might be reduced in both the vertebrate host and the parasites (60)(61)(62)(63). However, the knowledge of bacterial Sb(V) reduction is limited.…”

Section: Microbial Antimony Cyclementioning

confidence: 99%

Microbial Antimony Biogeochemistry: Enzymes, Regulation, and Related Metabolic Pathways

Wang

Oremland

et al. 2016

Appl Environ Microbiol

163

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e Antimony (Sb) is a toxic metalloid that occurs widely at trace concentrations in soil, aquatic systems, and the atmosphere. Nowadays, with the development of its new industrial applications and the corresponding expansion of antimony mining activities, the phenomenon of antimony pollution has become an increasingly serious concern. In recent years, research interest in Sb has been growing and reflects a fundamental scientific concern regarding Sb in the environment. In this review, we summarize the recent research on bacterial antimony transformations, especially those regarding antimony uptake, efflux, antimonite oxidation, and antimonate reduction. We conclude that our current understanding of antimony biochemistry and biogeochemistry is roughly equivalent to where that of arsenic was some 20 years ago. This portends the possibility of future discoveries with regard to the ability of microorganisms to conserve energy for their growth from antimony redox reactions and the isolation of new species of "antimonotrophs."

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“…It also increases ROS production in a human macrophage cell line (Hansen et al, 2011), causing parasite death. In the case of inorganic species of Sb, the toxicity mechanisms have not been studied in depth, and all mechanisms that have been raised are due to phys-icochemical similarities with As (De Boeck et al, 2003), suggesting that Sb can generate the aggregation of proteins and DNA damage, similar to As (Beyersmann and Hartwig, 2008;Tamás et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms underlying the toxic effects of antimony species in human embryonic kidney cells (HEK-293) and their comparison with arsenic species

2016

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-Antimony cytotoxicity was assessed in human embryonic kidney cells . Uptake, mitochondrial respiratory activity, ROS generation and diffusional kinetics were measured using fluorescence recovery after photobleaching (FRAP). Furthermore, the toxic effect induced by Sb was compared with As toxicity in regard to ROS generation and diffusional kinetics, which provides information on the protein aggregation process. Our results show a favored uptake of Sb(III) and a more severe effect, decreasing the mitochondrial activity more than in the presence of Sb(V). In comparison with As, the Sb species did not generate a significant increase in ROS generation, which was observed with As(III) and As(V). FRAP analysis yielded important information on the diffusion and binding dynamics of live cells in presence of these metalloids. The mobile fraction showed a strong decrease with the As species and Sb(III). The diffusion rate and the k off-rate were significantly decreased for the As and Sb species but were more strong in the presence of As(III).

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Reduction of Sb(V) in a Human Macrophage Cell Line Measured by HPLC-ICP-MS

Cited by 30 publications

References 25 publications

Profiling gene expression of antimony response genes in Leishmania (Viannia) panamensis and infected macrophages and its relationship with drug susceptibility

Profiling gene expression of antimony response genes in Leishmania (Viannia) panamensis and infected macrophages and its relationship with drug susceptibility

Microbial Antimony Biogeochemistry: Enzymes, Regulation, and Related Metabolic Pathways

Mechanisms underlying the toxic effects of antimony species in human embryonic kidney cells (HEK-293) and their comparison with arsenic species

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