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Arsenic trioxide affects the trace element balance in tissues in infected and healthy mice differently
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.
2009 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 29, no 1, p. 83-90Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Acquired infections are common in cancer patients. As2O3 treatment and infections affect the body's trace element balance. However, it is unknown whether concomitant infections cause adverse element interactions that endanger the safety and therapeutic effect of As2O3. MATERIALS AND METHODS: Coxsackievirus B3-infected mice were treated with 1.0 mg As2O3/kg bw for 3, 5 or 7 days. Arsenic, magnesium, iron, copper, zinc and selenium were measured (ICP-MS) in serum, heart, lung, liver, pancreas, kidney, intestine and brain. Virus in serum was followed by RT-PCR. RESULTS: The infection increased As in all organs except the intestine, whereas selenium concentration decreased in all organs except the heart and brain. The infection markedly reduced magnesium in the heart. CONCLUSION: As2O3 treatment results in pronounced differences in trace elements between healthy and infected individuals. This finding is important to consider, regarding treatment safety and efficacy, when As2O3 therapy is used in the clinical setting.

Place, publisher, year, edition, pages
2009. Vol. 29, no 1, p. 83-90
Keyword [en]
CVB3, Infection, Mice, Tissues, Trace elements
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-112036ISI: 000263731100010PubMedID: 19331136OAI: oai:DiVA.org:uu-112036DiVA, id: diva2:284417
Available from: 2010-01-07 Created: 2010-01-07 Last updated: 2017-12-12Bibliographically 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. p. 66
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)
Opponent
Supervisors
Available from: 2010-01-28 Created: 2010-01-07 Last updated: 2010-01-28Bibliographically approved

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