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HERO ID
2088479
Reference Type
Journal Article
Title
Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis
Author(s)
Perry, MR; Wyllie, S; Raab, A; Feldmann, J; Fairlamb, AH
Year
2013
Is Peer Reviewed?
1
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN:
0027-8424
EISSN:
1091-6490
Volume
110
Issue
49
Page Numbers
19932-19937
Language
English
PMID
24167266
DOI
10.1073/pnas.1311535110
Web of Science Id
WOS:000327744900064
URL
http://www.pnas.org/cgi/doi/10.1073/pnas.1311535110
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Abstract
The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. We have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime). To test this hypothesis, Leishmania donovani was serially passaged in mice exposed to arsenic in drinking water at environmentally relevant levels (10 or 100 ppm). Arsenic accumulation in organs and other tissues was proportional to the level of exposure and similar to that previously reported in human liver biopsies. After five monthly passages in mice exposed to arsenic, isolated parasites were found to be completely refractory to 500 μg⋅mL(-1) Pentostam compared with the control passage group (38.5 μg⋅mL(-1)) cultured in vitro in mouse peritoneal macrophages. Reassessment of resistant parasites following further passage for 4 mo in mice without arsenic exposure showed that resistance was stable. Treatment of infected mice with Pentostam confirmed that resistance observed in vitro also occurred in vivo. We conclude that arsenic contamination may have played a significant role in the development of Leishmania antimonial resistance in Bihar because inadequate treatment with antimonial drugs is not exclusive to India, whereas widespread antimonial resistance is.
Keywords
drug resistance; sodium antimony gluconate; treatment failure; environmental pollution
Tags
IRIS
•
Arsenic Hazard ID
PubMed
Considered New
PubMed
WOS
Considered New
2. Lit Search Updates through Oct 2015
PubMed
WOS
Considered
7. Other Studies through Oct 2015
Other
•
Arsenic (Inorganic)
1. Literature
Lit search updates through Oct 2015
3. Hazard ID Screening
Other potentially supporting studies
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