Expression profiles of genes related to melatonin and oxidative stress in human renal proximal tubule cells treated with antibiotic amphotericin B and its modified forms

Gola, Joanna; Skubis, Aleksandra; Sikora, Bartosz; Kruszniewska‐Rajs, Celina; Adamska, Jolanta; Mazurek, Urszula; Strzałka‐Mrozik, Barbara; Czernel, Grzegorz; Gagoś, Mariusz

doi:10.3906/biy-1505-52

Cited by 14 publications

(20 citation statements)

References 39 publications

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“…It is well known that the long-term application of some commercial antifungals, like amphotericin B, is limited due to the toxicity towards human kidney cells associated with generation of oxidative stress [71,72], as well as towards normal human dermal fibroblasts [73]. Therefore, an evaluation of novel antifungal agents for the potential to provoke oxidative stress in vivo and inflict the oxidative stress-mediated damages is of great importance for their further medical application.…”

Section: Oxidative Stress In Zebrafish Embryos Upon Exposure Tomentioning

confidence: 99%

Mononuclear silver(I) complexes with 1,7-phenanthroline as potent inhibitors of Candida growth

Savić

Vojnović

Glišić

et al. 2018

European Journal of Medicinal Chemistry

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Mononuclear silver(I) complexes with 1,7-phenanthroline (1,7-phen), [Ag(NO-O,O') (1,7-phen-N7)] (1) and [Ag(1,7-phen-N7)]X, X = ClO (2), CFSO (3), BF (4) and SbF (5) were synthesized and structurally characterized by NMR (H and C), IR and UV-Vis spectroscopy and ESI mass spectrometry. The crystal structures of 1, 3 and 4 were determined by single-crystal X-ray diffraction analysis. In all these complexes, 1,7-phen coordinates to the Ag(I) ion in a monodentate fashion via the less sterically hindered N7 nitrogen atom. The investigation of the solution stability of 1-5 in DMSO revealed that they are sufficiently stable in this solvent at room temperature. Complexes 1-5 showed selectivity towards Candida spp. in comparison to bacteria, effectively inhibiting the growth of four different Candida species with minimal inhibitory concentrations (MIC) between 1.2 and 11.3 μM. Based on the lowest MIC values and the lowest cytotoxicity against healthy human fibroblasts with selectivity index of more than 30, the antifungal potential was examined in detail for the complex 1. It had the ability to attenuate C. albicans virulence and to reduce epithelial cell damage in the cell infection model. Induction of reactive oxygen species (ROS) response has been detected in C. albicans, with fungal DNA being one of the possible target biomolecules. The toxicity profile of 1 in the zebrafish model (Danio rerio) revealed improved safety and activity in comparison to that of clinically utilized silver(I) sulfadiazine.

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Section: Oxidative Stress In Zebrafish Embryos Upon Exposure Tomentioning

confidence: 99%

Mononuclear silver(I) complexes with 1,7-phenanthroline as potent inhibitors of Candida growth

Savić

Vojnović

Glišić

et al. 2018

European Journal of Medicinal Chemistry

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“…A previous study has shown that the increase expression of MTNR1B is likely to decrease the release of insulin and lead to increasing risk of T2D (Tuomi et al 2016). Another research has confirmed amphotericin B with copper (II) ions (AmB–Cu 2+ ) as a complex formed by AmB and is likely to cause upregulation of MTNR1B (Gola et al 2015). In this study, it is illustrated that AmB is related to the oxidative injuries of the kidneys but studies about the influence of AmB–Cu 2+ on renal cells are rare (Gola et al 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Another research has confirmed amphotericin B with copper (II) ions (AmB–Cu 2+ ) as a complex formed by AmB and is likely to cause upregulation of MTNR1B (Gola et al 2015). In this study, it is illustrated that AmB is related to the oxidative injuries of the kidneys but studies about the influence of AmB–Cu 2+ on renal cells are rare (Gola et al 2015). Our evidence does not suggest a straightforward relationship between MTNR1B and eGFRcrea and T2D, but may provide a new insight for studying the common mechanism of eGFRcrea and T2D in genetic aspect.…”

Section: Discussionmentioning

confidence: 99%

Improved detection of genetic loci in estimated glomerular filtration rate and type 2 diabetes using a pleiotropic cFDR method

Liu

Zhou

et al. 2017

Mol Genet Genomics

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Genome-wide association studies (GWAS) have been shown to have the potential of explaining more of the “missing heritability” of complex human phenotypes by improving statistical approaches. Here, we applied a genetic-pleiotropy-informed conditional false discovery rate (cFDR) to capture additional polygenic effects associated with estimated glomerular filtration rate (creatinine) (eGFRcrea) and type 2 diabetes (T2D). The cFDR analysis improves the identification of pleiotropic variants by incorporating potentially shared genetic mechanisms between two related traits. The Q–Q and fold-enrichment plots were used to assess the enrichment of SNPs associated with eGFRcrea or T2D, and Manhattan plots were used for showing chromosomal locations of the significant loci detected. By applying the cFDR method, we newly identified 74 loci for eGFRcrea and 3 loci for T2D with the cFDR criterion of 0.05 compared with previous related GWAS studies. Four shared SNPs were detected to be associated with both eGFRcrea and T2D at the significant conjunction cFDR level of 0.05, and these shared SNPs had not been reported in previous studies. In addition, we used DAVID analysis to perform functional analysis of the shared SNPs’ annotated genes and found their potential hidden associations with eGFRcrea and T2D. In this study, the cFDR method shows the feasibility to detect more genetic variants underlying the heritability of eGFRcrea and T2D, and the overlapping SNPs identified could be regarded as candidate loci that provide a thread of genetic mechanisms between eGFRcrea and T2D in future research.

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“…The main limitation of the use of amphotericin B, however, is its high toxicity to human cells. One of the proposed mechanisms of the nephrotoxicity of amphotericin B is the induction of oxidative stress [11]. However, the mechanism of AmB toxicity has not been clearly elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, we studied the influence of modified forms of AmB: the complex of AmB with copper(II) ions (AmB-Cu 2+ ) and the oxidized form of AmB (AmBox). The first of them is less toxic for RPTECs while maintaining its antifungal activity [11,12]. Oxidized forms of AmB may occur in the patient's circulation during therapy, causing the observed side effects [13].…”

Section: Introductionmentioning

confidence: 99%

Changes in expression of genes related to caspases and BCL-2 family in RPTEC treated with amphotericin B and its modified forms

Gola

Simka

Strzałka‐Mrozik

et al. 2018

Ann. Acad. Med. Siles.

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I N T R O D U C T I O N :The main limitation of the use of amphotericin B (AmB)effective in the treatment of systemic fungal infectionsis its high toxicity to human cells. The mechanism of AmB toxicity is not clear. Caspase-related and BCL-2 proteins participate in the regulation of apoptosis. Thus, they may be involved in drug toxicity. In this study we evaluated the influence of AmB on the transcriptional activity of genes related to caspases and the BCL-2 family. We also tested the influence of modified forms of AmB: AmB-Cu 2+ (the complex with copper(II) ions) and the AmB-ox (oxidized form). M A T E R I A L A N D M E T H O D S :Human RPTECs (Renal Proximal Tubule Epithelial Cells) were treated with AmB, AmB-Cu 2+ and AmB-ox. Total RNA was extracted using the phenol-chloroform method. The expression profiles of genes related to caspase activity and BCL-2 were determined using oligonucleotide microarrays (HG-U133A 2.0, Affymetrix). Analysis included 67 ID related to caspases and 32 ID associated with BCL-2, according to the Affymetrix database. R E S U L T S : The analysis revealed upregulation of the BCL-2 and BCL2L1genes in the cells treated with AmB-Cu 2+ , in comparison to the control. In both the AmB and AmB-Cu 2+ -treated cells, differentiating genes were associated with inflammation and mitophagy activated by intrinsic signals. In the cells treated with AmB-ox, the BCL-2 genes were downregulated. C O N C L U S I O N S :The results suggest that AmB and AmB-Cu 2+ activate genes involved in the regulation of inflammation and autophagy induced by intrinsic signals, but overexpression of BCL-2 and BCL2L1 may protect AmB-Cu 2+ --treated cells from death. In the cells treated with AmB-ox extrinsic signals prevail, indicating the distinct molecular mechanism of its cytotoxicity.

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Expression profiles of genes related to melatonin and oxidative stress in human renal proximal tubule cells treated with antibiotic amphotericin B and its modified forms

Cited by 14 publications

References 39 publications

Mononuclear silver(I) complexes with 1,7-phenanthroline as potent inhibitors of Candida growth

Mononuclear silver(I) complexes with 1,7-phenanthroline as potent inhibitors of Candida growth

Improved detection of genetic loci in estimated glomerular filtration rate and type 2 diabetes using a pleiotropic cFDR method

Changes in expression of genes related to caspases and BCL-2 family in RPTEC treated with amphotericin B and its modified forms

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