ArticleBioMed research international2016
Evaluation of Hepatotoxicity with Treatment Doses of Flucytosine and Amphotericin B for Invasive Fungal Infections.
Article in BioMed research international, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Pharmacological assessment of drugs retained in the 1Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Exploring a Therapeutic Gold Mine: The Antifungal Potential of the Gold-Based Antirheumatic Drug Auranofin.International journal of molecular sciences · 2025Review
- Vitamin E Inhibits Oxidative Stress and Inflammation in Stress-Induced Gastritis via Modulating Nrf2 and NF-κB Signalling Pathways.Journal of cellular and molecular medicine · 2025Article
- The Anticancer Drug Bleomycin Shows Potent Antifungal Activity by Altering Phospholipid Biosynthesis.Microbiology spectrum · 2022Article
- Complexation with Random Methyl-β-Cyclodextrin and (2-Hidroxypropyl)-β-Cyclodextrin Enhances In Vivo Anti-Fibrotic and Anti-Inflammatory Effects of Chrysin via the Inhibition of NF-κB and TGF-β1/Smad Signaling Pathways and Modulation of Hepatic Pro/Anti-Fibrotic miRNA.International journal of molecular sciences · 2021Article
- Quinolines derivatives as promising new antifungal candidates for the treatment of candidiasis and dermatophytosis.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2020Article
- Effects of vitamin A and vitamin E on attenuation of amphotericin B-induced side effects on kidney and liver of male Wistar rats.Environmental science and pollution research international · 2020Article
- Pre-Existing Liver Disease and Toxicity of Antifungals.Journal of fungi (Basel, Switzerland) · 2018Review
- Article
- Flucytosine and Amphotericin B Coadministration Induces Dose-Related Renal Injury.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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