Intravenous itraconazole against experimental neutropenic Candida parapsilosis infection: efficacy after suppression of bacterial translocation

Carrer, Dionyssia-Pinelopi; Samonis, George; Droggiti, Dionyssia-Irini; Τσαγανός, Θωμάς; Pistiki, Aikaterini; Giamarellos‐Bourboulis, Evangelos J.

doi:10.1007/s10156-013-0627-4

Cited by 4 publications

(1 citation statement)

References 18 publications

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“…Itraconazole (ITR) is an azole broad-spectrum antifungal agent, and is orally administered for C. parapsilosis, C. albicans and C. glabrata infections (9)(10)(11). Generally, the treatment of fungal infections with ITR may be due not only to its direct antifungal effect, but also due to the induction of an immunomodulatory effect on the host defense miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis systems via the regulation of cytokine production (12).…”

Section: Introductionmentioning

confidence: 99%

miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis

Zhang

et al. 2018

Int J Mol Med

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Previous studies have indicated that monocyte chemoattractant protein-1 (MCP‑1), also referred to as C‑C motif chemokine ligand 2, has a significant role in the pathogenesis of sepsis, however, how microRNAs (miRs) contribute to this process remains to be fully elucidated. In the present study, using a mouse model of disseminated candidiasis, the renoprotective effect of itraconazole (ITR) and adenovirus‑delivered miR‑124 was investigated. The mice were treated with ITR (50 mg/kg) or transfected with miR‑124 mimics via tail‑vein injection 7 days prior to Candida albicans infection. The survival outcome was monitored following candidiasis‑induced sepsis with ITR or miR‑124 mimics treatment. The levels of pro‑inflammatory cytokines, including tumor necrosis factor‑α (TNF‑α), interleukin‑1β (IL‑1β) and IL‑6, were determined using enzyme‑linked immunosorbent assays. The mRNA and protein levels were assayed using reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. The results showed that ITR and miR‑124 mimics improved the survival outcome in candidiasis‑induced septic mice. The findings also indicated a significant downregulation in the serum levels of TNF‑α, IL‑1β and IL‑6 in the septic mice treated with ITR or miR‑124 mimics. Of note, ITR treatment significantly increased the expression of miR‑124 and decreased the levels of MCP‑1 in the kidneys of the septic mice. It was also shown that the overexpression of miR‑124 reduced the expression of MCP‑1 and attenuated candidiasis‑induced acute kidney injury (AKI) in septic mice. Transfection with miR‑124 mimics was equivalent to ITR in reducing the excessive inflammatory response and renal lesions in septic mice. These results provided evidence supporting the use of miR‑124 mimics as a therapeutic approach for attenuating candidiasis-induced AKI.

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Section: Introductionmentioning

confidence: 99%

miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis

Zhang

et al. 2018

Int J Mol Med

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Susceptibility profiles and clinical efficacy of antifungals against candida bloodstream isolates from critically ill patients: Focus on intravenous itraconazole

Giamarellos‐Bourboulis

Stamou

Maraki

et al. 2019

International Journal of Antimicrobial Agents

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Inhibition of VEGF-Flk-1 binding induced profound biochemical alteration in the hippocampus of a rat model of BBB breakdown by spider venom. A preliminary assessment using FT-IR spectroscopy

Mesquita-Britto¹,

Mendonça²,

Soares

et al. 2018

Neurochemistry International

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Phoneutria nigriventer spider venom (PNV) contains ion channels-acting neuropeptides that in rat induces transitory blood-brain barrier breakdown (BBBb) in hippocampus in parallel with VEGF upregulation. We investigated whether VEGF has a neuroprotective role by inhibiting its binding to receptor Flk-1 by itraconazole (ITZ). FT-IR spectroscopy examined the biochemical status of hippocampus and evaluated BBBb in rats administered PNV or ITZ/PNV at periods with greatest toxicity (1-2h), recovery (5h) and visual absence of symptoms (24h), and compared to saline and ITZ controls. The antifungal treatment before venom intoxication aggravated the venom effects and increased BBB damage. FT-IR spectra of venom, hippocampi of controls, PNV and ITZ-PNV showed a 1400 cm band linked to symmetric stretch of carboxylate and 1467 cm band (CH bending: mainly lipids) that were considered biomarker and reference bands, respectively. Inhibition of VEGF/Flk-1 binding produced marked changes in lipid/protein stability at 1-2h. The largest differences were observed in spectra regions assigned to lipids, both symmetric (2852 cm) and asymmetric (2924 and 2968 cm). Quantitative analyses showed greatest increases in the 1400 cm/1467 cm ratio also at 1h. Such changes at period of rats' severe intoxication referred to wavenumber region from 3106 cm to 687 cm assigning for C-H and N-H stretching of protein, Amide I, C=N cytosine, N-H adenine, Amide II, CH bending: mainly lipids, C-O stretch: glycogen, polysaccharides, glycolipids, z-type DNA, C-C, C-O and CH out-of-plane bending vibrations. We conclude that VEGF has a neuroprotective role and can be a therapeutic target in PNV envenomation. FT-IR spectroscopy showed to be instrumental for monitoring biochemical changes in this model of P. nigriventer venom-induced BBB disruption.

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Intravenous itraconazole against experimental neutropenic Candida parapsilosis infection: efficacy after suppression of bacterial translocation

Cited by 4 publications

References 18 publications

miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis

miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis

Susceptibility profiles and clinical efficacy of antifungals against candida bloodstream isolates from critically ill patients: Focus on intravenous itraconazole

Inhibition of VEGF-Flk-1 binding induced profound biochemical alteration in the hippocampus of a rat model of BBB breakdown by spider venom. A preliminary assessment using FT-IR spectroscopy

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