Cytotoxic and genotoxic effects of high concentrations of the immunosuppressive drugs cyclosporine and tacrolimus in MRC-5 cells

Cilião, Heloísa Lizotti; Ribeiro, Diego Luís; Camargo-Godoy, Rossana Batista Oliveira; Specian, Ana Flávia Leal; Serpeloni, Juliana Mara; Cólus, I.M.S.

doi:10.1016/j.etp.2014.11.008

Cited by 25 publications

(20 citation statements)

References 36 publications

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“…Moreover, this compound did not show cytotoxic effects in two selected cell lines routinely used for toxicity evaluation of chemicals [ 35 , 36 ], at concentrations even 10 times higher than those required to have an antimicrobial effect. On the contrary, at the highest concentrations tested, ceftriaxone showed a slight but significant cytotoxic effect on one of the two cell lines.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and biological evaluation of the progenitor of a new class of cephalosporin analogues, with a particular focus on structure-based computational analysis

et al. 2017

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We present the synthesis and biological evaluation of the prototype of a new class of cephalosporins, containing an additional isolated beta lactam ring with two phenyl substituents. This new compound is effective against Gram positive microorganisms, with a potency similar to that of ceftriaxone, a cephalosporin widely used in clinics and taken as a reference, and with no cytotoxicity against two different human cell lines, even at a concentration much higher than the minimal inhibitory concentration tested. Additionally, a deep computational analysis has been conducted with the aim of understanding the contribution of its moieties to the binding energy towards several penicillin-binding proteins from both Gram positive and Gram negative bacteria. All these results will help us developing derivatives of this compound with improved chemical and biological properties, such as a broader spectrum of action and/or an increased affinity towards their molecular targets.

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Section: Discussionmentioning

confidence: 99%

Synthesis and biological evaluation of the progenitor of a new class of cephalosporin analogues, with a particular focus on structure-based computational analysis

et al. 2017

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“…To evaluate the cell proliferation, the best choice is to measure total cellular protein content, which is not dependent of cell metabolism (Skehan et al 1990;Van Tonder et al 2015). For this, sulforhodamine B (SRB) or bromophenol blue (Skehan et al 1990;Cilião et al 2015;Serpeloni et al 2015) can be used as dye of cellular total protein content. The results obtained using the cell proliferation curves with bromophenol blue suggest that the three concentrations of all extracts evaluated did not alter the proliferative rate of either cell line in long-term treatment (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…A proliferation curve based on the determination of the total protein content was also performed using the technique proposed by Da Costa Lopes et al 2000, where the proteins were dyed with 1 % bromophenol blue. The steps were the same as performed by studies of Cilião et al (2015) and Serpeloni et al (2015).…”

Section: Cell Proliferation Curvesmentioning

confidence: 99%

LDH, proliferation curves and cell cycle analysis are the most suitable assays to identify and characterize new phytotherapeutic compounds

et al. 2016

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Brazilian flora biodiversity has been widely investigated to identify effective and safe phytotherapeutic compounds. Among the investigated plant species, the Byrsonima genus exhibits promising biological activities. This study aimed at evaluating the cytotoxicity of B. correifolia, B. verbascifolia, B. fagifolia and B. intermedia extracts using different assays in two cell lines (primary gastric and HepG2 cells). The different extract concentrations effects on cell viability were assayed using the MTT, aquabluer, neutral red and LDH assays. Non-cytotoxic concentrations were selected to generate cell proliferation curves and to assess cell cycle kinetics by flow cytometry. Byrsonima extracts differentially affected cell viability depending on the metabolic cellular state and the biological parameter evaluated. B. fagifolia and B. intermedia extracts exhibited lower cytotoxic effects than B. correifolia and B. verbascifolia in all assays. The results obtained with LDH and flow cytometry assays were more reliable, suggesting that they can be useful in the screening for herbal medicine and to further characterize these extracts as phytotherapeutic compounds.

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“…Similarly, tacrolimus and mycophenolate mofetil treated individuals exhibit enhanced free radicals contributing to the oxidative damage, lipid peroxidation production, induced DNA lesions, and reduced mitochondrial membrane potential [Ferjani et al, ]. A recent in vitro study using plasma concentration values of cyclosporine and tacrolimus observed the induction of genetic damage in both comet and MN assays in human fibroblasts [Cilião et al, ]. These studies would support our findings showing over time increases in the levels of genetic damage in KT patients.…”

Section: Discussionmentioning

confidence: 94%

DNA damage in kidney transplant patients. Role of organ origin

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Rodríguez-Ribera

Coll

et al. 2017

Environ and Mol Mutagen

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Chronic kidney disease (CKD) patients are characterized by elevated levels of genomic damage. This damage increases when kidney function decreases being maximum in hemodialysis patients. As kidney transplantation improves renal function, and it is related with better survival, the aim of our study was to evaluate potential changes in DNA damage levels after kidney transplantation, and comparing living donor recipients with cadaveric donor recipients. The alkaline comet assay was used to determine DNA breaks and oxidative damaged DNA; and the micronucleus assay was used to determine chromosomal breakage and/or aneuploidy. Fifty CKD patients were followed up after 6 and 12 months of their kidney transplantation. All patients increased their genomic damage levels after 6 and 12 months of renal transplantation, compared with those observed before transplantation, despite of the improvement of their metabolic functions. Donor advanced age correlated positively with higher DNA damage. Genomic damage was lower in living donor transplants with respect to cadaveric donor transplants. Our conclusion is that DNA damage increased in kidney transplantation patients, whereas their renal function improved. Higher levels of DNA damage were found in cadaveric donor transplants when compared to living donor transplants. Environ. Mol. Mutagen. 58:712-718, 2017. © 2017 Wiley Periodicals, Inc.

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Cytotoxic and genotoxic effects of high concentrations of the immunosuppressive drugs cyclosporine and tacrolimus in MRC-5 cells

Cited by 25 publications

References 36 publications

Synthesis and biological evaluation of the progenitor of a new class of cephalosporin analogues, with a particular focus on structure-based computational analysis

Synthesis and biological evaluation of the progenitor of a new class of cephalosporin analogues, with a particular focus on structure-based computational analysis

LDH, proliferation curves and cell cycle analysis are the most suitable assays to identify and characterize new phytotherapeutic compounds

DNA damage in kidney transplant patients. Role of organ origin

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