Chronic arsenic exposure and microbial drug resistance

McConville, Malcolm J.; Ralph, Stuart A.

doi:10.1073/pnas.1319659110

Cited by 10 publications

(6 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Decreased levels of neutrophils, monocytes, and eosinophils provided additional evidence for arsenic-driven immune derangement. Arsenic-induced immunosuppression has the potential to predispose people to infections and in the long term, may contribute to microbial drug resistance [ 43 ]. The reduction of these cells through apoptotic induction has previously been demonstrated in patients treated with arsenic trioxide and in mice treated with sodium arsenite [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Coenzyme Q10 protected against arsenite and enhanced the capacity of 2,3-dimercaptosuccinic acid to ameliorate arsenite-induced toxicity in mice

Mwaeni

Nyariki

Jillani

et al. 2021

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

Background Arsenic poisoning affects millions of people. The inorganic forms of arsenic are more toxic. Treatment for arsenic poisoning relies on chelation of extracellularly circulating arsenic molecules by 2,3-dimecaptosuccinic acid (DMSA). As a pharmacological intervention, DMSA is unable to chelate arsenic molecules from intracellular spaces. The consequence is continued toxicity and cell damage in the presence of DMSA. A two-pronged approach that removes extracellular arsenic, while protecting from the intracellular arsenic would provide a better pharmacotherapeutic outcome. In this study, Coenzyme Q10 (CoQ10), which has been shown to protect from intracellular organic arsenic, was administered separately or with DMSA; following oral exposure to sodium meta-arsenite (NaAsO2) – a very toxic trivalent form of inorganic arsenic. The aim was to determine if CoQ10 alone or when co-administered with DMSA would nullify arsenite-induced toxicity in mice. Methods Group one represented the control; the second group was treated with NaAsO2 (15 mg/kg) daily for 30 days, the third, fourth and fifth groups of mice were given NaAsO2 and treated with 200 mg/kg CoQ10 (30 days) and 50 mg/kg DMSA (5 days) either alone or in combination. Results Administration of CoQ10 and DMSA resulted in protection from arsenic-induced suppression of RBCs, haematocrit and hemoglobin levels. CoQ10 and DMSA protected from arsenic-induced alteration of WBCs, basophils, neutrophils, monocytes, eosinophils and platelets. Arsenite-induced dyslipidemia was nullified by administration of CoQ10 alone or in combination with DMSA. Arsenite induced a drastic depletion of the liver and brain GSH; that was significantly blocked by CoQ10 and DMSA alone or in combination. Exposure to arsenite resulted in significant elevation of liver and kidney damage markers. The histological analysis of respective organs confirmed arsenic-induced organ damage, which was ameliorated by CoQ10 alone or when co-administered with DMSA. When administered alone, DMSA did not prevent arsenic-driven tissue damage. Conclusions Findings from this study demonstrate that CoQ10 and DMSA separately or in a combination, significantly protect against arsenic-driven toxicity in mice. It is evident that with further pre-clinical and clinical studies, an adjunct therapy that incorporates CoQ10 alongside DMSA may find applications in nullifying arsenic-driven toxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Coenzyme Q10 protected against arsenite and enhanced the capacity of 2,3-dimercaptosuccinic acid to ameliorate arsenite-induced toxicity in mice

Mwaeni

Nyariki

Jillani

et al. 2021

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

show abstract

“…Additionally, due to factors such as side effects and the parenteral mode of treatment, many patients are unable to complete the course of treatment, leading to low compliance and an increase in resistance against the pentavalent antimonials. Currently, these first-line antimony treatments are no longer effective in certain areas, such as North Bihar in India, because of chronic exposure to high levels of As in the water. − …”

Section: Leishmaniasismentioning

confidence: 99%

Metal Compounds against Neglected Tropical Diseases

et al. 2018

View full text Add to dashboard Cite

Many first-line treatments for neglected tropical diseases identified by the World Health Organization (WHO) are limited by one or more of the following: the development of drug resistance, toxicity, and side effects, lack of selectivity, narrow therapeutic indices, route of administration, and bioavailability. As such, there is an urgent need to develop viable alternatives to overcome these limitations. The following review provides an overview of all existing metal complexes studied and evaluates the status of these complexes on the respective disease of choice.

show abstract

“…In fact, over 60% of newly diagnosed human cases in Bihar, India are SSG-resistant (Rijal et al, 2003). Additionally, arsenic contaminated drinking water, prevalent throughout many regions of India, has been shown to increase the cross-resistance of L. donovani toward antimonials (McConville and Ralph, 2013). Furthermore, clinical isolates from the Bihar region have begun showing signs of ampB resistance (Purkait et al, 2012) and the elongated half-life of miltefosine increases chances of parasite-acquired resistance (Mishra and Singh, 2013).…”

Section: Introductionmentioning

confidence: 99%

Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles

Collier

Peine

Gautam

et al. 2016

International Journal of Pharmaceutics

View full text Add to dashboard Cite

Leishmaniasis is a disease caused by parasites of Leishmania sp., which effects nearly 12 million people worldwide and is associated with treatment complications due to widespread parasite resistance toward pathogen-directed therapeutics. The current treatments for visceral leishmaniasis (VL), the systemic form of the disease, involve pathogen-mediated drugs and have long treatment regimens, increasing the risk of forming resistant strains. One way to limit emergence of resistant pathogens is through the use of host-mediated therapeutics. The host-mediated therapeutic AR-12, which is FDA IND-approved for cancer treatment, has shown activity against a broad spectrum of intracellular pathogens; however, due to hydrophobicity and toxicity, it is difficult to reach therapeutic doses. We have formulated AR-12 into microparticles (AR-12/MPs) using the novel biodegradable polymer acetalated dextran (Ace-DEX) and used this formulation for the systemic treatment of VL. Treatment with AR-12/MPs significantly reduced liver, spleen, and bone marrow parasite loads in infected mice, while combinatorial therapies with amphotericin B had an even more significant effect. Overall, AR-12/MPs offer a unique, host-mediated therapy that could significantly reduce the emergence of drug resistance in the treatment of VL.

show abstract

Chronic arsenic exposure and microbial drug resistance

Cited by 10 publications

References 22 publications

Coenzyme Q10 protected against arsenite and enhanced the capacity of 2,3-dimercaptosuccinic acid to ameliorate arsenite-induced toxicity in mice

Coenzyme Q10 protected against arsenite and enhanced the capacity of 2,3-dimercaptosuccinic acid to ameliorate arsenite-induced toxicity in mice

Metal Compounds against Neglected Tropical Diseases

Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles

Contact Info

Product

Resources

About