ArticleProceedings of the National Academy of Sciences of the United States of America2013
Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 66 citations in OpenAlex.
- Arsenic disrupts autophagosome-lysosome fusion in a zinc dependent manner across multiple human skin and lung cells lines.Archives of toxicology · 2026Article
- Chronic arsenic exposure and hsa-miR-186 overexpression causes transcriptome-wide differential alternative splicing contributing to skin carcinogenesis in human HaCaT cell line.Archives of toxicology · 2025Article
- Dysregulation of mRNA expression by hsa-miR-186 overexpression in arsenic-induced skin carcinogenesis.Toxicology and applied pharmacology · 2025Article
- Drugs for Vector-Borne Protozoal Diseases in a One Health Scenario. A European Perspective.ACS infectious diseases · 2024Review
- Antimony resistance and gene expression inParasitology · 2024Review
- Arsenic exposure to mouse visceral leishmaniasis model through their drinking water linked to the disease exacerbation via modulation in host protective immunity: a preclinical study.Scientific reports · 2023Article
- AS3MT facilitates NLRP3 inflammasome activation by mCell biology and toxicology · 2023Article
- The adaptive roles of aneuploidy and polyclonality in Leishmania in response to environmental stress.EMBO reports · 2023Article
- Environmental behavior, human health effect, and pollution control of heavy metal(loid)s toward full life cycle processes.Eco-Environment & Health · 2022Review
- Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Identification of 3-Methoxycarpachromene and Masticadienonic Acid as New Target Inhibitors against Trypanothione Reductase fromMolecules (Basel, Switzerland) · 2021Article
- MRPA-independent mechanisms of antimony resistance in Leishmania infantum.International journal for parasitology. Drugs and drug resistance · 2020Article
- Regulation of Translation in the Protozoan ParasiteInternational journal of molecular sciences · 2020Review
- Gallic acid and MiADMSA reversed arsenic induced oxidative/nitrosative damage in rat red blood cells.Heliyon · 2020Article
- Arsenite exposure suppresses adipogenesis, mitochondrial biogenesis and thermogenesis via autophagy inhibition in brown adipose tissue.Scientific reports · 2019Article
- Article
- The gut microbiome is required for full protection against acute arsenic toxicity in mouse models.Nature communications · 2018Article
- Characterisation of a putative glutamate 5-kinase from Leishmania donovani.The FEBS journal · 2018Article
- Molecular Preadaptation to Antimony Resistance in Leishmania donovani on the Indian Subcontinent.mSphere · 2018Article
- Evaluating drug resistance in visceral leishmaniasis: the challenges.Parasitology · 2018Review
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5 authors at 2 institutions in 1 country.
Funding
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.
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