Cytogenetic genotoxicity of amoxicillin

PubMedID: 19790260Amoxicillin (AMO), a drug used in the treatment of infections caused by susceptible bacteria, has been evaluated for its ability to induce genotoxicity in human peripheral blood lymphocytes. The potential genotoxic effects of AMO were investigated in vitro by the sister chromatid exchange (SCE), chromosomal aberration (CA), and micronucleus (MN) tests. The cells were treated with 400, 600, 800, and 1,000 µg/ml AMO in the presence and absence of a metabolic activator (S9 mix), respectively. In this study, AMO did not induce SCEs or CAs in human peripheral blood lymphocytes both in the presence and absence of the metabolic activator. AMO concentration-dependently decreased the proliferation index (PI) in the absence of the metabolic activation for 24-hr treatment period. Mitotic index (MI) was generally found to have been reduced when compared with the negative control but not with the solvent control in cultures treated with AMO for 24 hr. AMO did not decrease the PI and MI in the presence of the metabolic activator. Furthermore, AMO neither induced the formation of MN nor decreased the nuclear division index in human peripheral blood lymphocytes both in the presence and absence of the metabolic activator. According to the present results, we suggest that AMO does not pose genotoxic risk for patients who are under therapy against bacterial infections. © 2009 Wiley-Liss, Inc

In vitro genotoxicity and cytotoxicity of cefixime in human peripheral blood lymphocytes

Cefixime (CFX) is a third-generation cephalosporin antibiotic that is widely used to treat Neisseria gonoirhoeae infection. Although some studies have reported the genotoxic and cytostatic/cytotoxic effects of cephalosporins, to the best of our knowledge, no studies have been performed on the genotoxic and cytotoxic effects of CFX in eukaryotic test systems. A global consensus about the genotoxicity of cephalosporins is still not feasible. Thus, the aim of the present study was to evaluate the potential genotoxic and cytostatic/ cytotoxic effects of CFX in human peripheral blood lymphocytes. In this study, CFX did not induce chromosome aberrations (CAs) at 24-And 48-hr treatment periods. However, it was obvious that CFX induced more chromosomal-Type breaks compared to the chromatid types at both the 24-And 4S-hr treatments. No significant increase in the mean sister chromatid exchange (SCE) values was observed for the 24-And 48-hr treatment periods; however, the maximum SCE number showed an excessive ina-ease in some lymphocytes at the 48-hr treatment. CFX did not induce micronucleus (MN) formation at both treatment times. However, CFX significantly decreased the proliferation index (PI) and mitotic index (MI) for both the 24-And 48-hr treatment periods. Furthermore, CFX caused a concentration- dependent decrease in the nuclear division index (NDI) for the 48-hr treatment (r = -0.979. P < 0.05). Our study showed that CFX was not genotoxic in cultured human peripheral lymphocytes. However, the excessive induction of SCEs in single cells is indicative of its mutagenic potential. In addition, the cytostatic/cytotoxic effects of CFX may have deleterious effects on the immune system which may increase the susceptibility of the patient against bacterial infections

In vitro genotoxicity and cytotoxicity of a particular combination of pemetrexed and cefixime in human peripheral blood lymphocytes

This study aims to find the genotoxic and cytotoxic effects of a particular combination of pemetrexed (PMX) and cefixime (CFX) in human peripheral blood lymphocytes. Chromosome aberration (CA), sister chromatid exchange (SCE), and micronucleus (MN) tests were used to assess genotoxicity. Whereas, the cytotoxicity was evaluated by using mitotic index (MI), proliferation index (PI), and nuclear division index (NDI). Our tests were proceeded with concentrations of 12.5 + 450, 25 + 800, 37.5 + 1150, and 50 + 1500 µg/mL of a mixture of PMX and CFX separately for 24 hr and 48 hr.The combination of PMX + CFX did not induce the CA or SCE in human peripheral blood lymphocytes when compared with both the control and the solvent control. MN in human peripheral blood lymphocytes was not significantly increased after treatment with a particular combination of PMX + CFX. However, PMX + CFX significantly decreased the MI, PI and NDI at all concentrations for 24- and 48-hr treatment periods when compared with both controls. Generally, PMX + CFX inhibited cell proliferation more than positive control (MMC) and showed a higher cytotoxic effect than MMC at both treatment periods. These results were compared with individual effects of PMX and CFX. As a result, it was observed that a particular combination of PMX + CFX was not genotoxic. However, the combination synergistically increase cytotoxicity in human peripheral blood lymphocytes. © 2015, Istifli and Topaktas; licensee Springer

Genotoxicity of pemetrexed in human peripheral blood lymphocytes

Pemetrexed (PMX) is an antineoplastic antifolate used in the treatment of non-small cell lung cancer, mesothelioma and several types of neoplasms. Its toxicity in tumor cells has been linked with the potent inhibition of thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase, and subsequent depletion of both purine and pyrimidine nucleotides. However, cytogenetic toxicity of PMX in non-diseased cells has not been adequately studied; despite the increasing data on the DNA-damaging potential of antineoplastic agents on normal cells. In the present study, the genotoxic potential of PMX was evaluated in peripheral blood lymphocytes obtained from healthy human subjects using chromosome aberration (CA), sister chromatid exchange (SCE) and micronucleus (MN) assays as the cytogenetic damage markers. Human peripheral blood lymphocytes were exposed to four different concentrations (25, 50, 75 and 100 µg/mL) of PMX for 24- and 48-h treatment periods. PMX significantly increased the formation of CA in 24-h treatment, but not in 48-h treatment. PMX did not increase the mean SCE frequency in 24- and 48-h treatment periods; however, there was a striking increase (although not statistically significant, p > 0.05) in the number of SCEs at 25 µg/mL (24- and 48-h treatment) and 50 µg/mL (24-h treatment) due to an increase of SCE at the single-cell level. Interestingly, PMX did not induce MN formation in either 24- or 48-h treatment periods. PMX strongly decreased the mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) in 24- and 48-h treatment periods. Our results suggest that PMX has a potent cytotoxic effect against human peripheral blood lymphocytes at concentrations which are reached in vivo in the blood plasma. © 2012 Springer Science+Business Media Dordrecht.FEF2011D8Acknowledgments This work was supported by Cukurova University Research Fund (FEF2011D8)

In vitro genotoxic effects of benzoyl peroxide in human peripheral lymphocytes [Insan periferal lenfositlerinde benzol peroksit'in in vitro genotoksik etkileri]

The aim of the present research was to investigate the genotoxic potency of benzoyl peroxide (BPO), a whitener of flour and cheese, using in vitro sister chromatid exchange (SCE), chromosome aberration (CA), and micronucleus (MN) tests in human peripheral lymphocytes. Cells were exposed to 25, 50, 75, and 100 µ/mL concentrations of BPO for 24 and 48 h. BPO induced SCEs only at the highest concentration (100 µ/mL) for 48 h treatment. Furthermore, BPO induced CAs at 75 and 100 µ/mL concentrations for 24 h treatment, and at all concentrations for 48 h treatment. BPO induced CAs in a dose-dependent manner for 24 and 48 h treatment periods. Increased level of MN formation induced by BPO was only observed for the 48 h treatment period at the 2 highest concentrations (75 and 100 µ/mL). Statistically significant reductions in the proliferation index (PI) and mitotic index (MI) were only detected in cultures for the 48-h treatment period. © TÜBITAK

In vitro cytogenetic toxicity of bezafibrate in human peripheral blood lymphocytes

Bezafibrate (BF) is a peroxisome proliferator-activated receptor (PPAR) agonist used as a lipid-lowering agent to treat both the familial or acquired combined forms of hyperlipidemia. BF is the only available fibrate drug that acts on all PPAR subtypes of ?, ß, and ?. Although there are studies that indicate a genotoxic potential associated with the use of fibrates, to our knowledge, the genotoxicity of BF in human peripheral blood lymphocytes has not been studied. In the present study, the genotoxic potential of BF was evaluated using chromosome aberration (CA) and micronucleus (MN) assays in peripheral blood lymphocytes of healthy human subjects. In addition, a high performance liquid chromatography (HPLC) method was used to identify and quantitate the drug passage into the cells. Human peripheral blood lymphocytes were exposed to four different concentrations (100, 175, 250 and 325 µg/mL) of BF for 24- and 48-h treatment periods. As shown by HPLC, in spite of significant passage of BF into human peripheral blood lymphocytes in 24- and 48-h treatment periods, BF was not found to increase the CA and MN frequency. On the other hand, exposing cells to BF for 24- and 48-h treatment periods caused significant concentration-dependent decreases in the mitotic index (r = -0.995, p < 0.01 for 24-h; r = -0.992, p < 0.01 for 48-h) and nuclear division index (r = -0.990, p < 0.01 for 24-h; r = -0.981, p < 0.01 for 48-h). Our results suggest that BF has cytotoxic effect on cultured human peripheral blood lymphocytes. © 2017, Springer Science+Business Media Dordrecht.FEF2013YL11This study was sponsored by Cukurova University Research Fund; Grant Number FEF2013YL11

Adsorption of Cd(II), Cu(II) and Ni(II) ions by Lemna minor L.: Effect of physicochemical environment

PubMedID: 16051430The free floating macrophyte Lemna minor L. was harvested locally. Untreated, acid pretreated (H2SO4), alkali pretreated (NaOH) biomass were used for adsorption of copper, cadmium and nickel ions from aqueous solutions. The effect of initial pH, initial metal concentration and multi metal interaction were carried out in a batch system. The equilibrium adsorption was reached within 40-60 min. The Langmuir and Freundlich models were used for describing of adsorption isotherm data. The maximum adsorption capacities of alkali pretreated biomass were determined as 83, 69 and 59 mg g-1 for the Cd(II), Cu(II) and Ni(II) ions, respectively. The pseudo first- and second-order intraparticle diffusion models were used to describe the adsorption kinetics. The experimental data fitted to pseudo second-order kinetic. Adsorption capacity decreased with acid pretreatment; however alkali pretreatment was not affected significantly adsorption capacity and adsorption capacity a little increased according to native biomass. The FT-IR results of Lemna biomass showed that biomass has different functional groups and these functional groups are able to react with metal ions in aqueous solution. © 2005 Elsevier B.V. All rights reserved.This study was supported by Cukurova University Research fund (project no. FEF 2004 BAP7)

In vitro evaluation of the protective effects of 4-thujanol against mitomycin-C and cyclophosphamide-induced genotoxic damage in human peripheral lymphocytes

PubMedID: 223234774-Thujanol (sabinene hydrate), a bicyclic monoterpene alcohol, is found in the essential oils of many aromatic and medicinal plants and is widely used as a fragrance and flavouring agent in many different products. The aim of this study was to evaluate the protective effects of 4-thujanol against the genotoxic effects induced by mitomycin C (MMC) and cyclophosphamide (CP) in human lymphocytes, using the chromosome aberrations, sister chromatid exchanges, and micronucleus tests, in the absence and in the presence of S9 mix, respectively. The cells were treated with 0.25 µg/mL MMC and 28 µg/mL CP as alone and cotreated with 13 + 0.25, 26 + 0.25, and 52 + 0.25 µg/mL 4-thujanol + MMC and with 13 + 28, 26 + 28, and 52 + 28 µg/mL 4-thujanol + CP as a mixture. The present study showed that 4-thujanol was unable to reduce the genetic damage induced by MMC, in the absence of S9 mix. On the other hand, probably the metabolites of 4-thujanol act as an antagonist and markedly antagonize CP-induced genotoxicity, in the presence of S9 mix. In general, 4-thujanol + MMC and 4-thujanol + CP decreased the mitotic index, proliferation index and nuclear division index to the same extent or more than those of individual exposure of MMC or CP. In conclusion, 4-thujanol significantly reduced (p < 0.001) the genotoxic damage induced by CP but not MMC when compared with the respective positive control alone. We can suggest that 4-thujanol may improve the chemopreventive effects and may also reduce the harmful side effects of CP, which is widely used in chemotherapy against cancer, without reducing its antiproliferative activities. © 2012, SAGE Publications. All rights reserved

Alpha-linolenic acid confers protection on mice renal cells against cisplatin-induced nephrotoxicity

Cisplatin is an antineoplastic agent used in the treatment of various types of solid tumors. Despite the dose-dependency of its antineoplastic effect, the high risk for nephrotoxicity frequently precludes the use of higher doses. ?-Linolenic acid (ALA), a carboxylic acid having three cis double bonds, is an essential fatty acid required for health and can be acquired via foods that contain ALA or supplementation of foods high in ALA. Previous studies have shown that ALA demonstrates anti-cancer, anti-inflammatory, and anti-oxidative effects. In this study, we show the protective effect of ALA on cisplatin-induced renal toxicity associated with oxidative stress in mice using biochemical parameters. The mice were randomly assigned into four experimental groups. Group 1 (control group) were administered physiological saline solution for 9 days; group 2 (ALA group) received 200 mg/kg alpha-linolenic acid via gavage for 9 days; group 3 (CIS group) received 100 mg/kg intraperitoneal (i.p.) CIS for 9 days; and group 4 (ALA + CIS group) received 100 mg/kg i.p. CIS and followed by ALA 200 mg/kg via gavage for 9 days. Alpha-linolenic acid significantly reduced the expression of myeloperoxidase (MPO), phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the ALA + CIS group compared to the CIS group. Furthermore, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) quantities were significantly elevated in the ALA + CIS group when compared to the CIS group. ALA significantly decreased the levels of Bax and cleaved caspase-3, while significantly increasing the level of bcl-2, an anti-apoptotic protein, in the ALA + CIS group than in the CIS group. Finally, histopathological examination in renal tissue showed that the significant edematous damage induced by CIS administration alone was reduced in ALA + CIS group. In conclusion, our findings show that ALA is beneficial to CIS-induced nephrotoxicity in mice via its anti-inflammatory and anti-oxidative effects. © 2019, Springer Nature B.V.Firat University Scientific Research Projects Management Unit: FBA-2018-10148This study has been funded by Cukurova University Scientific Research Projects Unit (FBA-2018-10148). Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations

The effects of 4-thujanol on chromosome aberrations, sister chromatid exchanges and micronucleus in human peripheral blood lymphocytes

4-Thujanol, a bicyclic monoterpene alcohol, is present in the essential oils of many medicinal and aromatic plants. It is commonly used as a fragrance and flavouring ingredient in a lot ofdifferent products. The potential genotoxic effects of 4-thujanol on human peripheral blood lymphocytes (PBLs) were investigated in vitro by the chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) tests. The cells were treated with 13, 26 and 52 µg/mL 4-thujanol in the presence and absence of a metabolic activator (S9 mix). 4-Thujanol induced CA (P<0.001) and MN formation (P<0.05) at all concentrations (13, 26 and 52 µg/mL) in the presence and absence of the S9 mix without a concentration-dependent manner. However, the treatment of peripheral lymphocytes with 4-thujanol did not produce a statistical difference in the frequency of SCEs when compared with control group. Furthermore, this monoterpene did not significantly decrease the mitotic index (MI), proliferation index (PI), and nuclear division index (NDI). In conclusion, 4-thujanol had a significant clastogenic effect at the tested concentrations (13, 26 and 52 µg/mL) for human PBLs. In addition, no cytotoxic and/or cytostatic effects were observed regardless of the concentrations used. This work presents the first report on genotoxic properties of 4-thujanol. © Springer Science+Business Media B.V. 2011.109T546Acknowledgements This investigation was supported by a grant from The Scientific and Technical Research Council of Turkey, Ankara (TUBITAK, Project No. 109T546)