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Evaluation of Hepatotoxicity with Treatment Doses of Flucytosine and Amphotericin B for Invasive Fungal Infections
Joint Authors
Hermenean, Anca
Folk, Alexandra
Cotoraci, Coralia
Balta, Cornel
Suciu, Maria
Herman, Hildegard
Boldura, Oana Maria
Paiusan, Lucian
Ardelean, Aurel
Dinescu, Sorina
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-02-02
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
Invasive fungal infection is a well-known cause of morbidity and mortality in immunocompromised patients.
In this study we aimed to evaluate the hepatotoxicity induced by combined therapy of flucytosine and amphotericin B, at three different doses administered to mice for 14 days: 50 mg/kg flucytosine and 300 μg/kg amphotericin B; 100 mg/kg flucytosine and 600 μg/kg amphotericin B; 150 mg/kg flucytosine and 900 μg/kg amphotericin B.
Liver injuries were evaluated by analysis of optic and electron microscopy samples, changes in TNF-α, IL-6, and NF-κB inflammation markers levels of expression, and evaluation of mRNA profiles.
Histological and ultrastructural analysis revealed an increase in parenchymal and portal inflammation in mice and Kupffer cells activation.
Combined antifungal treatment stimulated activation of an inflammatory pathway, demonstrated by a significant dose-dependent increase of TNF-α and IL-6 immunoreactivity, together with mRNA upregulation.
Also, NF-κB was activated, as suggested by the high levels found in hepatic tissue and upregulation of target genes.
Our results suggest that antifungal combined therapy exerts a synergistic inflammatory activation in a dose-dependent manner, through NF-κB pathway, which promotes an inflammatory cascade during inflammation.
The use of combined antifungal therapy needs to be dose limiting due to the associated risk of liver injury, especially for those patients with hepatic dysfunction.
American Psychological Association (APA)
Folk, Alexandra& Cotoraci, Coralia& Balta, Cornel& Suciu, Maria& Herman, Hildegard& Boldura, Oana Maria…[et al.]. 2016. Evaluation of Hepatotoxicity with Treatment Doses of Flucytosine and Amphotericin B for Invasive Fungal Infections. BioMed Research International،Vol. 2016, no. 2016, pp.1-9.
https://search.emarefa.net/detail/BIM-1098108
Modern Language Association (MLA)
Folk, Alexandra…[et al.]. Evaluation of Hepatotoxicity with Treatment Doses of Flucytosine and Amphotericin B for Invasive Fungal Infections. BioMed Research International No. 2016 (2016), pp.1-9.
https://search.emarefa.net/detail/BIM-1098108
American Medical Association (AMA)
Folk, Alexandra& Cotoraci, Coralia& Balta, Cornel& Suciu, Maria& Herman, Hildegard& Boldura, Oana Maria…[et al.]. Evaluation of Hepatotoxicity with Treatment Doses of Flucytosine and Amphotericin B for Invasive Fungal Infections. BioMed Research International. 2016. Vol. 2016, no. 2016, pp.1-9.
https://search.emarefa.net/detail/BIM-1098108
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1098108