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Sequential effects of daily arsenic trioxide treatment on essential and nonessential trace elements in tissues in mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
2008 (English)In: Anti-Cancer Drugs, ISSN 0959-4973, E-ISSN 1473-5741, Vol. 19, no 8, 812-8 p.Article in journal (Refereed) Published
Abstract [en]

Despite arsenic's (As) toxic potential, arsenic trioxide (As2O3) is used as a safe and effective treatment in acute promyelocytic leukaemia. However, it is unknown whether such therapy influences the balance of other trace elements in the body. In this study, mice were treated intraperitoneally daily with 1.0 mg As2O3/kg bw for 3, 5 or 7 days. As, and seven essential and nonessential trace elements with the potential to interact with As, were measured through inductively coupled plasma-mass spectrometry in serum, heart, lung, liver, pancreas, kidney, intestine and brain. As2O3 supplementation increased As in all target tissues on day 3, thereafter reaching an almost steady state. The major findings in other elements were a sequential decrease in serum zinc (on day 7 by 64%; P<0.001), and a decrease in selenium in the pancreas on day 3 (9%; P<0.05), in the intestine on day 3 (30%; P<0.001) and finally, in the brain on days 5 (12%; P<0.05) and 7 (15%; P<0.01). Changes in magnesium, iron, copper, cadmium and mercury were minor and inconsistent. This study suggests that supplementation with other trace elements may be beneficial when As2O3 treatment regimens are used in the clinic.

Place, publisher, year, edition, pages
2008. Vol. 19, no 8, 812-8 p.
Keyword [en]
acute promyelocytic leukaemia treatment, arsenic trioxide, serum, tissues, trace elements
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-88772DOI: 10.1097/CAD.0b013e32830c456bISI: 000259277600008PubMedID: 18690093OAI: oai:DiVA.org:uu-88772DiVA: diva2:159051
Available from: 2009-02-26 Created: 2009-02-06 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Arsenic Influences Virus Replication in Experimental Coxsackievirus B3 Infection
Open this publication in new window or tab >>Arsenic Influences Virus Replication in Experimental Coxsackievirus B3 Infection
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Trace elements are essential for the host defence against infections, and during common infections, the balance of trace elements is changed in serum and tissues. Supplementation with selenium (Se), an essential trace element, is known to decrease the severity of coxsackievirus B3 (CVB3) infection in mice. Even the non-essential trace element arsenic (As) seems to influence the replication of some viruses.

During the course of an acute CVB3 infection in mice, Se concentrations decreased in most tissues and were negatively correlated to viral load in our study. However, As concomitantly decreased in most tissues. As has previously been shown to interfere with the balance of essential trace elements. However, in the present study As supplementation in healthy mice resulted in minor effects on seven studied trace elements in serum and tissues. The effects of As supplementation were more pronounced in CVB3-infected mice, with an increase in As, but a decrease in Se in most tissues when compared with non-infected mice.

As supplementation during CVB3 infection in mice decreased viral RNA concentrations in the brain (97%) and pancreas (75%), two of the target organs of this infection. In vitro experiments indicate that As caused an impaired virion assembly or release. In vivo, infection-induced expression of the host defence-associated genes nuclear factor κB (NFκB) and interferon γ (IFN-γ) were unaffected by As supplementation, except for an earlier increase in IFN-γ in the brain.

In conclusion, a clinically relevant dose of As decreased the replication of CVB3 in vitro and in vivo. This antiviral effect in vivo was not related to changes in specific trace elements or in the host’s immune-mediated defence. Although the mechanism underlying the observed effect on viral replication remains to be further elucidated, As seems to be an intriguing trace element to study in the pursuit of new antiviral drugs.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 66 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 513
Keyword
coxsackievirus B3, trace elements, arsenic, selenium, virology, IFN-γ, NFκB
National Category
Infectious Medicine
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:uu:diva-112049 (URN)978-91-554-7702-8 (ISBN)
Public defence
2010-02-19, Hörsalen, Klinisk mikrobiologi, Akademiska sjukhuset, ingång D1, Dag Hammarskjölds väg 17, Uppsala, 13:15 (Swedish)
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Supervisors
Available from: 2010-01-28 Created: 2010-01-07 Last updated: 2010-01-28Bibliographically approved

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