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1.
Sci Rep ; 14(1): 6175, 2024 03 14.
Article in English | MEDLINE | ID: mdl-38485748

ABSTRACT

Our main goal was to design and synthesize novel lomefloxacin derivatives that inhibit the topoisomerase II enzyme, leading to potent anticancer activity. Lomefloxacin derivatives substituted at position 3 and 7 were synthesized and screened for cytotoxic activity utilizing 60 different human cancer cell lines. Furthermore, compounds 3a,b,c,e that revealed potent broad-spectrum anticancer activity (with mean percent GI more than 47%) were further evaluated using five dose concentrations and calculating the GI50. Compound 3e was then evaluated for cell cycle analysis and demonstrated cell cycle arrest at the G2-M phase. Moreover, the mechanism of action was determined by determining the topoisomerase inhibitory activity and the molecular modeling study. Compounds 3a,b,c,e showed broad spectrum anticancer activity. Lomefloxacin derivative 5f showed selective cytotoxic activity against melanoma SK-MEL-5 cell line. Compound 3e demonstrated comparable topoisomerase II inhibition to doxorubicin with IC50 of 0.98 µM.


Subject(s)
Antineoplastic Agents , Fluoroquinolones , Humans , Molecular Structure , Structure-Activity Relationship , Cell Line, Tumor , Antineoplastic Agents/pharmacology , DNA Topoisomerases, Type II/metabolism , Cell Proliferation , Drug Screening Assays, Antitumor , Molecular Docking Simulation , Dose-Response Relationship, Drug
2.
Sci Total Environ ; 926: 171872, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38521253

ABSTRACT

Heterojunctions composed of cobalt-based materials and carbon materials have been recognized as the efficient catalysts for peroxymonosulfate (PMS) activation to generate reactive oxygen species for the removal of environmental contaminants. However, the role of carbon materials in promoting the heterojunction systems has not been fully understood. This study synthesized a heterojunction material of graphene sheets encapsulating Co3O4 (GCO-500) through the pyrolysis of cobalt MOF and applied it to activate PMS for the removal of lomefloxacin. The results showed a high removal rate of 93.59 % with a degradation rate of k1 = 0.0156 min-1. Co3O4 clusters was encapsulated within ultrathin graphene sheets (<2 nm). DFT calculations revealed that graphene layers improve the electron transfer ability of Co3O4 and increased the d-band center of Co3O4 (-1.61 eV) that promote the adsorption of PMS on GCO-500 (-1.32 eV). In the meanwhile, organic pollutant was enriched in graphene layers with high adsorption energy (-13.08 eV), which greatly enhanced the degradation efficiency of pharmaceuticals. This study provides an effective catalyst for PMS activation and sheds light on the fundamental electronic-level understanding of cobalt-based and carbon heterojunction catalysts in PMS activation.

3.
Article in English | MEDLINE | ID: mdl-38502862

ABSTRACT

Lomefloxacin (LMF), a third-generation fluoroquinolone antibacterial agent, is often used to treat bacterial and mycoplasma infections. However, due to its prolonged half-life and slow metabolism, it is prone to residues in animal-derived foods, posing a potential food safety risk. Therefore, it is particularly urgent and important to establish a method for detecting lomefloxacin. In this study, direct and indirect competitive fluorescence-linked immunosorbent assay (dc-FLISA and ic-FLISA) based on quantum dots (QDs) was established for the detection of LMF. As for dc-FLISA, the half-maximal inhibitory concentration (IC50) and limit of detection (LOD) were 0.84 ng/mL, 0.04 ng/mL, respectively, the detection ranges from 0.08 to 9.11 ng/mL. The IC50 and LOD of ic-FLISA were 0.43 ng/mL and 0.03 ng/mL, respectively, meanwhile the detection ranges from 0.05 to 3.49 ng/mL. The recoveries of dc-FLISA and ic-FLISA in animal-derived foods (milk, fish, chicken, and honey), ranged from 95.8% to 105.2% and from 96.3% to 103.4%, respectively, with the coefficients of variation less than 8%. These results suggest that the dc-FLISA and ic-FLISA methods, which are based on QD labelling, are highly sensitive and cost-effective, and can be effectively used to detect LMF in animal-derived foods.


Subject(s)
Chickens , Fluoroquinolones , Food Contamination , Milk , Quantum Dots , Quantum Dots/chemistry , Animals , Food Contamination/analysis , Fluoroquinolones/analysis , Milk/chemistry , Honey/analysis , Fluorescence , Anti-Bacterial Agents/analysis , Enzyme-Linked Immunosorbent Assay , Food Analysis
4.
Environ Sci Pollut Res Int ; 31(3): 4140-4153, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38102422

ABSTRACT

The facile fabrication of low-cost adsorbents possessing high removal efficiency and convenient separation property is an urgent need for water treatment. Herein, magnetic activated carbon was synthesized from spent coffee grounds (SCG) by Fe-catalyzed CO2 activation at 800 °C for 90 min, and magnetization and pore formation were simultaneously achieved during heat treatment. The sample was characterized by N2 adsorption-desorption, XRD, VSM, SEM, and FTIR. Batch adsorption experiments were conducted using lomefloxacin (LMO) as the probing pollutant. Preparation mechanism was revealed by TG-FTIR and XRD. Experimental results showed that Fe3O4 derived from Fe species can be reduced to Fe by carbon at high temperatures, followed by subsequent reoxidation to Fe3O4 by CO2, and the redox cycle between Fe and Fe3O4 favored the formation of pores. The promotion effects of Fe species on CO2 activation can be quantitatively reflected by the yield of CO as the signature gaseous product, and the suitable activation temperate range was determined to be 675 to 985 °C. The BET surface area, total pore volume, and saturated magnetization value of the product were 586 m2 g-1, 0.327 cm3 g-1, and 11.59 emu g-1, respectively. The Langmuir model was applicable for the adsorption isotherm data for LMO with the maximum adsorption capacity of 95 mg g-1, and thermodynamic analysis revealed that the adsorption process was endothermic and spontaneous. This study demonstrated that Fe-catalyzed CO2 activation was an effective method of converting SCG into magnetic separable adsorbent for LMO removal from aqueous medium.


Subject(s)
Anti-Bacterial Agents , Fluoroquinolones , Water Pollutants, Chemical , Adsorption , Anti-Bacterial Agents/analysis , Charcoal/analysis , Coffee , Carbon Dioxide/analysis , Iron/analysis , Magnetic Phenomena , Catalysis , Water Pollutants, Chemical/analysis , Kinetics
5.
Chemosphere ; 340: 139907, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37633615

ABSTRACT

Phosphorus-modified copper ferrite (P-CuFe2O4) nanoparticles were prepared by a simple sol-gel auto-combustion process and used for the photocatalytic ozonation of lomefloxacin (LOM). The morphology, crystallinity, and structure of the synthesized CuFe2O4 and P-CuFe2O4 nanoparticles were investigated using various techniques. The high-performance liquid chromatography (HPLC) analysis revealed that the degradation of LOM achieved a 99% reduction after a duration of 90 min in the photocatalytic ozonation system. In accordance with the charge-to-mass ratio, four intermediates were proposed with the help of their fragments obtained in LC-MS/MS. The degradation kinetics of lomefloxacin followed a pseudo-first order reaction, and the degradation mechanism was proposed based on the results. P0.035Cu0.965Fe2O4 showed the highest total organic carbon (TOC) removal with 20.15% in 90 min, highest specific surface area and the highest fluoride and ammonium production using the ion chromatography (IC). The experimental results obtained from the electron paramagnetic resonance (EPR) analysis indicated that the modified P-CuFe2O4 samples exhibited significantly elevated levels of superoxide (.O2-) production compared to the CuFe2O4 samples. The findings of this study demonstrate that the introduction of phosphorus modification into the copper ferrite photocatalyst led to an augmentation of both the specific surface area and the total pore volume. Furthermore, the incorporation of phosphorus served to promote the efficient separation of electron-hole pairs by effectively trapping electrons in the conduction band, hence enhancing the degradation efficiency.


Subject(s)
Nanoparticles , Ozone , Chromatography, Liquid , Copper , Tandem Mass Spectrometry
6.
J Pharm Biomed Anal ; 234: 115552, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37393690

ABSTRACT

In terms of risk assessment especially for the impurities with different ultraviolet responses, quantitative analysis without the availability of corresponding reference substances currently poses a challenge. In this study, a universal response method was established for the quantitative analysis of photodegradable impurities in lomefloxacin hydrochloride ear drops by high performance liquid chromatography-charged aerosol detector (HPLC-CAD) for the first time. The chromatographic conditions and CAD parameters were optimized for a good separation and sensitivity. The uniform response of developed method was validated by impurity reference substances with different ultraviolet responses. In the gradient compensation HPLC-CAD method validation, good linearities were obtained with coefficient of determination (R2) all greater than 0.999 for lomefloxacin and impurity reference substances. The average recoveries of the impurities were 98.63%- 102.18% by UV and 97.92%- 102.57% by CAD, respectively. RSDs all were less than 2.5% for intra-day and inter-day precision by UV and CAD, with good precision and accuracy. The correction factor experimental results showed that the developed method provided a uniform response to the impurities with differences chromophores in lomefloxacin. The effects of packaging materials and excipients on the photodegradation were also investigated using the developed method. The results of correlation analysis showed that the packaging materials with low light transmittance and the organic excipients (glycerol and ethanol) could significantly improve the stability of lomefloxacin hydrochloride ear drops. The developed HPLC-CAD quantification method was a reliable and universal response method for quantitative analysis of impurities in the lomefloxacin. This study also revealed the key factors affecting the photodegradation of lomefloxacin hydrochloride ear drops, which guided enterprises to improve drug prescription and packaging materials and ensure the public medication safety.


Subject(s)
Excipients , Photolysis , Chromatography, Liquid , Chromatography, High Pressure Liquid/methods , Aerosols/chemistry
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 292: 122399, 2023 May 05.
Article in English | MEDLINE | ID: mdl-36724684

ABSTRACT

The purpose of the present work was to establish a fast and convenient strategy for lomefloxacin analysis using a fluorimetric approach. The methodology was based on the complex formation of the drug with aluminum ion to give a product having high fluorescence. Adding sodium dodecyl sulfate led to further boosting the intensity of fluorescence which was recorded at 429 nm after excitation at 332 nm. The relationship of emission intensity with lomefloxacin concentration was linear at 10-130 ng mL-1 with a correlation coefficient of 0.9996. The quantitation limit was 11.4 ng mL-1 and detection limit was 3.8 ng mL-1. The reaction conditions were carefully studied which included the pH, buffer type, its concentration, the type and concentration of surfactant and the diluting solvent. The method was utilized to quantify the aforementioned drug in tablet formulations and in real human plasma with high accuracy and reliability.


Subject(s)
Fluoroquinolones , Metals , Humans , Spectrometry, Fluorescence/methods , Reproducibility of Results , Fluoroquinolones/analysis , Solvents
8.
Environ Sci Pollut Res Int ; 30(11): 29125-29142, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36409411

ABSTRACT

Antibiotic was detected in many environments, and it had posed a serious threat to human health. The advanced oxidation process has been considered an effective way to treat antibiotics. In this work, using industrial waste red mud (RM) as raw material, a series of modified RM (MRM-T; T donates the calcination temperature) was obtained via a facile calcination method and applied to activate sodium bisulfite (NaHSO3) for the lomefloxacin (LOM) degradation. Among all MRM-T, MRM-700 exhibited superior catalytic activity, and approximately 89% of LOM (10 mg/L) was degraded at 30 min through the activation of NaHSO3 ([NaHSO3] = 0.5 g/L) by MRM-700 ([MRM-700] = 0.9 g/L). Moreover, the kinetic constant of LOM removal in the MRM-700/NaHSO3 system (0.082 min-1) was 16.4 times higher than that of the RM-raw/NaHSO3 system (0.005 min-1). The as-synthesized product of MRM-700 was characterized by N2 adsorption-desorption isotherms, X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and Raman spectra. The result indicated that the catalyst possessed excellent pore structure, high specific area, and abundant Fe3+ sites, and the lattice of Fe2O3 was doped after calcination, both of which were favorable for the activation of NaHSO3. The quenching experiment proved that •SO4- and •OH- active species were produced in MRM-700/NaHSO3 system, and •SO4- played a dominant role in LOM removal. In addition, the potential LOM degradation pathway was analyzed via UPLC-MS technology and density functional theory (DFT) calculation, and the toxicity of the treated LOM solution was tested by the culture of mung bean sprouts. This study not only provided a feasible strategy for the valuable use of RM to activate NaHSO3 but also offered a cost-effective catalyst for the efficient removal of pollutants in wastewater.


Subject(s)
Tandem Mass Spectrometry , Humans , Chromatography, Liquid , Catalysis
9.
Anal Bioanal Chem ; 414(20): 6047-6054, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35687152

ABSTRACT

Recently, polymer-protected gold nanoparticles (AuNPs) have attracted extensive attention due to their good catalytic activities. However, how to regulate their catalytic activities by changing the polymer chain morphologies or the interactions between the ligands and the analytes through external stimuli is still a great challenge. This study describes a simple synthesis of AuNPs capped by thermo-responsive poly(N,N-dimethylacrylamide) (PDMAM). In comparison with three kinds of PDMAMs@AuNPs, PDMAM-2@AuNPs exhibited better peroxidase-mimic ability via the catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) with hydrogen peroxide (H2O2) to generate oxidized TMB (oxTMB). Interestingly, its catalytic activity could be regulated by changing environmental temperature. Importantly, the addition of the antibiotic lomefloxacin endowed the PDMAM-2@AuNPs with enhancement in catalytic efficiency due to electrostatic interactions and the increased levels of reactive oxygen species. Based on this principle, a protocol for highly selective and sensitive monitoring of lomefloxacin has been constructed with the color change from pale blue to deep blue. The ultraviolet-visible absorbance of oxTMB at the wavelength of 650 nm showed a good linear relationship with antibiotic concentration in the range of 0.25-10.0 µM (R2 = 0.990). The limit of detection was 0.1 µM. The practical application of the proposed protocol with the promoted peroxidase-mimic activity for the measurement of lomefloxacin in capsules was realized.


Subject(s)
Gold , Metal Nanoparticles , Acrylamides , Anti-Bacterial Agents , Colorimetry/methods , Fluoroquinolones , Hydrogen Peroxide , Peroxidase , Polymers
10.
Cells ; 11(12)2022 06 19.
Article in English | MEDLINE | ID: mdl-35741100

ABSTRACT

Phototoxicity induced by antibiotics is a real problem in health care. The discontinuation of antibiotic therapy due to a phototoxic reaction can lead to the development of resistant strains. Fluoroquinolones are widely used antibiotics that exhibit phototoxic activity under UVA radiation. The purpose of the study was to examine the redox status of human dermal fibroblasts exposed to UVA radiation and treated with lomefloxacin, the most phototoxic fluoroquinolone. Lomefloxacin alone was found to have an antiproliferative activity on fibroblasts by affecting the cell cycle. In addition, the drug caused a redox imbalance associated with the decreased expression of catalase and glutathione peroxidase. UVA radiation increased the drug cytotoxicity and oxidative stress induced by lomefloxacin. The decrease in cell viability was accompanied by a high level of reactive oxygen species and extensive changes in the antioxidant levels. The revealed data indicate that the phototoxic action of lomefloxacin results from both increased reactive oxygen species production and an impaired antioxidant defense system. Considering all of the findings, it can be concluded that lomefloxacin-induced phototoxic reactions are caused by an oxidoreductive imbalance in skin cells.


Subject(s)
Anti-Infective Agents , Dermatitis, Phototoxic , Quinolones , Anti-Bacterial Agents/adverse effects , Anti-Infective Agents/pharmacology , Antioxidants/pharmacology , Dermatitis, Phototoxic/etiology , Fibroblasts , Fluoroquinolones/pharmacology , Humans , Oxidation-Reduction , Quinolones/pharmacology , Reactive Oxygen Species
11.
J Liposome Res ; 32(1): 74-82, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34697998

ABSTRACT

The present study aimed to develop lomefloxacin-loaded ethosomal vesicles intended to be applied topically for treating skin infections. Ethosomes were prepared using the cold method. The formulation variables were optimized using 22 factorial design and Design Expert® software for analyzing the data statistically and graphically using response surface plots. Phosphatidylcholine (X1) and ethanol (X2) were chosen as the independent variables, while the dependent variables comprised entrapment efficiency (Y1), vesicles size (Y2) and zeta potential (Y3). The optimized ethosomes were subsequently incorporated into Carbopol® 940 gel and characterized for rheological behaviour, in-vitro release, ex-vivo skin permeation and deposition. The ex-vivo permeation and skin deposition studies showed better results compared to drug solutions. In a nutshell, the ethosomal vesicles were found to be a promising carrier demonstrating enhanced topical delivery of lomefloxacin.


Subject(s)
Liposomes , Skin Absorption , Administration, Cutaneous , Lecithins , Liposomes/metabolism , Skin/metabolism
12.
Luminescence ; 37(2): 255-262, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34806313

ABSTRACT

A new sensitive and instantaneous spectrofluorimetric method for efficient determination of lomefloxacin (LMX) in its pure, dosage form and human plasma was designed. The developed method depends on formation of a metal-chelation compound of LMX as a ligand with zinc(II) in a buffer of acetate (pH 5.5). The following parameters; type of metal, concentration of metal, pH, type of buffer and diluting solvent were optimized. After carefully investigation; 0.2 mM zinc, 2.0 ml acetate buffer (pH 5.5) and water as diluting solvent were set as optimum reaction conditions. Under these conditions, a large increase in the intensity of the fluorescence of LMX was attained at 450 after excitation at 284 nm. The limits of detection and quantification were 5.8 and 1.9 ng ml-1 , respectively, with linearity range of 10.0 to 500.0 ng ml-1 . The binding mode of LMX and zinc(II) ion (Zn2+ ) was found to be 2:1, respectively, and confirmed by Job's plot method. Furthermore, it extended to the analysis of LMX in the spiked plasma of humans with percentage recovery (98.70 ± 0.97 to 100.30 ± 1.69%, n = 3).


Subject(s)
Fluoroquinolones , Zinc , Humans , Solvents , Spectrometry, Fluorescence
13.
Cells ; 10(11)2021 10 27.
Article in English | MEDLINE | ID: mdl-34831123

ABSTRACT

Fluoroquinolones cause phototoxic reactions, manifested as different types of skin lesions, including hyperpigmentation. The disturbances of melanogenesis indicate that fluoroquinolones may affect cellular processes in melanocytes. It has been reported that these antibiotics may bind with melanin and accumulate in pigmented cells. The study aimed to examine the changes in melanogenesis in human normal melanocytes exposed to UVA radiation and treated with lomefloxacin and moxifloxacin, the most and the least fluoroquinolone, respectively. The obtained results demonstrated that both tested fluoroquinolones inhibited melanogenesis through a decrease in tyrosinase activity and down-regulation of tyrosinase and microphthalmia-associated transcription factor production. Only lomefloxacin potentiated UVA-induced melanogenesis. Under UVA irradiation lomefloxacin significantly enhanced melanin content and tyrosinase activity in melanocytes, although the drug did not cause an increased expression of tyrosinase or microphthalmia-associated transcription factor. The current studies revealed that phototoxic activity of fluoroquinolones is associated with alterations in the melanogenesis process. The difference in phototoxic potential of fluoroquinolones derivatives may be connected with various effects on UVA-induced events at a cellular level.


Subject(s)
Fluoroquinolones/pharmacology , Melanins/biosynthesis , Melanocytes/metabolism , Ultraviolet Rays , Cell Death/drug effects , Cell Death/radiation effects , Cell Survival/drug effects , Cell Survival/radiation effects , Fluoroquinolones/chemistry , Gene Expression Regulation/drug effects , Gene Expression Regulation/radiation effects , Humans , Melanocytes/drug effects , Melanocytes/radiation effects , Microphthalmia-Associated Transcription Factor/genetics , Microphthalmia-Associated Transcription Factor/metabolism , Monophenol Monooxygenase/genetics , Monophenol Monooxygenase/metabolism , Moxifloxacin/chemistry , Moxifloxacin/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism
14.
Drug Chem Toxicol ; 44(3): 238-249, 2021 May.
Article in English | MEDLINE | ID: mdl-30822164

ABSTRACT

Lomefloxacin (LF) is interesting as a model molecule from a safety point of view because of its high potential for serious adverse drug effects (i.e. phototoxic reactions). In this study, MCM-41 mesoporous silica nanoparticles (MCM-41) were loaded with lomefloxacin, aiming to overcome the drug's intrinsic cytotoxicity. The good biocompatibility of the empty drug carrier (0.1-1.0 mg/ml) was established by the absence of red blood cell lysis (hemolysis assay). The cytotoxicity of empty MCM-41 and lomefloxacin-loaded MCM-41 (LF-MCM-41) was evaluated by using a battery of in vitro cytotoxicity assays: Alamar blue, lactate dehydrogenase release and reactive oxygen species formation by dichlorofluorescein assay. Three cell cultures models: hepatoma HepG2, fibroblasts L929 and endothelial EA.hy926 cells were used to compare the cytotoxicity and reactive oxygen species formation by free drug, empty MCM-41, and LF-MCM-41. The findings from the study indicated that empty MCM-41 (0.1-1.0 mg/ml) showed a low cytotoxic potential in HepG2, followed by L929 and EA.hy926 cells. Lomefloxacin loading in MCM-41 mesoporous silica nanocarrier reduced the cytotoxicity of the free lomefloxacin, especially in the high concentration (1.0 mg/ml MCM-41, containing 120 µg/ml LF). L929 and EA.hy926 cells were more sensitive to the protective effects of LF-MCM-41, compared to HepG2 cells. The results indicate that an improvement in lomefloxacin safety might be expected after incorporation in an appropriate drug delivery system.


Subject(s)
Drug Delivery Systems , Fluoroquinolones/administration & dosage , Nanoparticles , Silicon Dioxide/chemistry , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/toxicity , Cell Line , Drug Carriers/chemistry , Endothelial Cells/drug effects , Fibroblasts/drug effects , Fluoroquinolones/toxicity , Hep G2 Cells , Humans , Mice , Reactive Oxygen Species/metabolism
15.
Int J Mol Sci ; 21(24)2020 Dec 19.
Article in English | MEDLINE | ID: mdl-33352719

ABSTRACT

Phototoxicity of fluoroquinolones is connected with oxidative stress induction. Lomefloxacin (8-halogenated derivative) is considered the most phototoxic fluoroquinolone and moxifloxacin (8-methoxy derivative) the least. Melanin pigment may protect cells from oxidative damage. On the other hand, fluoroquinolone-melanin binding may lead to accumulation of drugs and increase their toxicity to skin. The study aimed to examine the antioxidant defense system status in normal melanocytes treated with lomefloxacin and moxifloxacin and exposed to UV-A radiation. The obtained results demonstrated that UV-A radiation enhanced only the lomefloxacin-induced cytotoxic effect in tested cells. It was found that fluoroquinolones alone and with UV-A radiation decreased superoxide dismutase (SOD) activity and SOD1 expression. UV-A radiation enhanced the impact of moxifloxacin on hydrogen peroxide-scavenging enzymes. In turn, lomefloxacin alone increased the activity and the expression of catalase (CAT) and glutathione peroxidase (GPx), whereas UV-A radiation significantly modified the effects of drugs on these enzymes. Taken together, both analyzed fluoroquinolones induced oxidative stress in melanocytes, however, the molecular and biochemical studies indicated the miscellaneous mechanisms for the tested drugs. The variability in phototoxic potential between lomefloxacin and moxifloxacin may result from different effects on the antioxidant enzymes.


Subject(s)
Antioxidants/metabolism , Fluoroquinolones/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Melanocytes/pathology , Moxifloxacin/pharmacology , Skin/pathology , Ultraviolet Rays/adverse effects , Anti-Bacterial Agents/pharmacology , Antioxidants/radiation effects , Catalase/metabolism , Catalase/radiation effects , Glutathione Peroxidase/metabolism , Glutathione Peroxidase/radiation effects , Humans , Melanins/metabolism , Melanocytes/metabolism , Melanocytes/radiation effects , Oxidative Stress , Skin/drug effects , Skin/metabolism , Superoxide Dismutase/metabolism , Superoxide Dismutase/radiation effects
16.
Int J Mol Sci ; 21(23)2020 Nov 25.
Article in English | MEDLINE | ID: mdl-33255659

ABSTRACT

Melanoma, the most dangerous type of cutaneous neoplasia, contributes to about 75% of all skin cancer-related deaths. Thus, searching for new melanoma treatment options is an important field of study. The current study was designed to assess whether the condition of mild and low-dose UVA radiation augments the lomefloxacin-mediated cytotoxic, growth-inhibitory and pro-apoptotic effect of the drug in melanoma cancer cells through excessive oxidative stress generation. C32 amelanotic and COLO829 melanotic (BRAF-mutant) melanoma cell lines were used as an experimental model system. The combined exposure of cells to both lomefloxacin and UVA irradiation caused higher alterations of redox signalling pathways, as shown by intracellular reactive oxygen species overproduction and endogenous glutathione depletion when compared to non-irradiated but lomefloxacin-treated melanoma cells. The obtained results also showed that lomefloxacin decreased both C32 and COLO829 cells' viability in a concentration-dependent manner. This effect significantly intensified when melanoma cells were exposed to UVA irradiation and the drug. For melanoma cells exposed to lomefloxacin or lomefloxacin co-treatment with UVA irradiation, the concentrations of the drug that decreased the cells' viability by 50% (EC50) were found to be 0.97, 0.17, 1.01, 0.18 mM, respectively. Moreover, we found that the redox imbalance, mitochondrial membrane potential breakdown, induction of DNA fragmentation, and changes in the melanoma cells' cell cycle distribution (including G2/M, S as well as Sub-G1-phase blockade) were lomefloxacin in a dose-dependent manner and were significantly augmented by UVA radiation. This is the first experimental work that assesses the impact of excessive reactive oxygen species generation upon UVA radiation exposure on lomefloxacin-mediated cytotoxic, growth-inhibitory and pro-apoptotic effects towards human melanoma cells, indicating the possibility of the usage of this drug in the photochemotherapy of malignant melanoma as an innovative medical treatment option which could improve the effectiveness of therapy. The obtained results also revealed that the redox imbalance intensification mediated by the phototoxic potential of fluoroquinolones may be considered as a more efficient treatment model of malignant melanoma and may constitute the basis for the development of new compounds with a high ability to excessive oxidative stress generation upon UVA radiation in cancer cells.


Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , Fluoroquinolones/pharmacology , Melanoma/drug therapy , Antineoplastic Agents/pharmacology , Apoptosis/radiation effects , Cell Line, Tumor , Cell Proliferation/radiation effects , Cell Survival/drug effects , Cell Survival/radiation effects , Combined Modality Therapy , Cytotoxins/pharmacology , Dose-Response Relationship, Radiation , Humans , Melanoma/genetics , Melanoma/pathology , Melanoma/radiotherapy , Membrane Potential, Mitochondrial/drug effects , Membrane Potential, Mitochondrial/radiation effects , Oxidative Stress/drug effects , Oxidative Stress/radiation effects , Proto-Oncogene Proteins B-raf/genetics , Reactive Oxygen Species/metabolism , Ultraviolet Rays
17.
Molecules ; 25(22)2020 Nov 11.
Article in English | MEDLINE | ID: mdl-33187198

ABSTRACT

The oxidation of lomefloxacin (LOM) and balofloxacin (BAL) under the influence of azo initiator of radical reactions of 4,4'-azobis(4-cyanopentanoic acid) (ACVA) and H2O2 was examined. Oxidation using H2O2 was performed at room temperature while using ACVA at temperatures: 40, 50, 60 °C. Additionally, the oxidation process of BAL under the influence of KMnO4 in an acidic medium was investigated. New stability-indicating HPLC methods were developed in order to evaluate the oxidation process. Chromatographic analysis was carried out using the Kinetex 5u XB-C18 100A column, Phenomenex (Torrance, CA, USA) (250 × 4.6 mm, 5 µm particle size, core shell type). The chromatographic separation was achieved while using isocratic elution and a mobile phase with the composition of 0.05 M phosphate buffer (pH = 3.20 adjusted with o-phosphoric acid) and acetonitrile (87:13 v/v for LOM; 80:20 v/v for BAL). The column was maintained at 30 °C. The methods were validated according to the ICH guidelines, and it was found that they met the acceptance criteria. An oxidation process followed kinetics of the second order reaction. The most probable structures of LOM and BAL degradation products formed were assigned by the UHPLC/MS/MS method.


Subject(s)
Azo Compounds/chemistry , Chromatography, High Pressure Liquid/methods , Fluoroquinolones/chemistry , Hydrogen Peroxide/chemistry , Potassium Permanganate/chemistry , Tandem Mass Spectrometry/methods , Valerates/chemistry , Drug Stability , Hydrolysis , Kinetics , Limit of Detection , Linear Models , Oxidation-Reduction , Oxygen/chemistry , Reproducibility of Results , Temperature
18.
J Hazard Mater ; 399: 122966, 2020 11 15.
Article in English | MEDLINE | ID: mdl-32516652

ABSTRACT

In this study, bimetal layered double hydroxides (CoxCuy-LDHs) containing a carbonate interlayer were synthesized using coprecipitation with a variety of Co/Cu mole ratios. Meanwhile, the corresponding layered double oxides (CoxCuy-LDOs) were prepared as controls. In this study, Electrical energy per order was performed to evaluate economic analysis. Correspondingly, we found that CoxCuy-LDHs possessed a significantly better PMS activation capability than the corresponding metal oxide composite (Co3O4/CuO). Compared with other CoxCuy-LDHs, Co2Cu1 LDH possessed the best PMS activation capability for LOM degradation and the lowest electrical energy per order (EE/O) value during the reaction. Additionally, Co2Cu1 LDH presented an excellent stability and worked over a wide pH range. The hydroxide states of Co(III), Co(II), Cu(I) and Cu(II) were all able to activate PMS, indicating that there were many active sites on the surface of Co2Cu1 LDH. The involvement of radicals in this reaction system was determined via scavenger experiments and electron paramagnetic resonance (EPR). Meanwhile, it's worth noting that a mathematical model was developed to quantify the involvement of SO4- and OH. Subsequently, we determined PMS activation mechanism and LOM decomposition pathway for the PMS/Co2Cu1 LDH system.


Subject(s)
Fluoroquinolones , Peroxides , Oxides
19.
Parasitol Res ; 119(6): 1955-1968, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32399722

ABSTRACT

Coccidiosis is a crucial parasitic disease of the poultry industry. As a result of the enormous global economic losses and the increased resistance to the conventional anticoccidial agents, there is a continuous need to find new anticoccidials. Here, the anticoccidial effect of the fluoroquinolone lomefloxacin versus diclazuril in experimentally infected broilers was tested for the treatment of Eimeria tenella infection. Ninety 14-day-old Cobb strain broiler chickens were allocated into five groups, each with 18 chicks. Group 1 (G1) was separated as an uninfected negative control and received no treatment; group 2 (G2), infected untreated (positive control); group 3 (G3), infected and treated with lomefloxacin at a dose rate of 100 ppm in drinking water; group 4 (G4), infected and treated with diclazuril at a dose rate of 2.5 ppm in drinking water; group 5 (G5), infected and treated with lomefloxacin at a dose rate of 100 ppm plus diclazuril at dose rate of 2.5 ppm in drinking water. Clinical signs, mortality rates, number of oocysts per gram of faeces (OPG), growth performance parameters (weight gain: WG and feed conversion ratio: FCR), lesion scoring, haematological and serum biochemical analyses, antioxidant biomarkers and histopathologic inspection of the caeca were used as evaluation criteria for the anticoccidial efficacy of both lomefloxacin and diclazuril. The findings herein showed that administration of lomefloxacin and/or diclazuril improved growth performance parameters (WG, FCR) and significantly (P ≤ 0.05) reduced OPG, and diminished the severity of bloody diarrhoea and mortalities. Additionally, haematological indices and serum biochemical parameters such as ALT, AST, ALP, creatinine, uric acid, total proteins, albumin and globulin were improved. Finally, a significant elevation in the levels of the antioxidant biomarkers was observed in the chicks of G3, G4 and G5 as compared with those of G2.


Subject(s)
Chickens/parasitology , Coccidiosis/veterinary , Coccidiostats/pharmacology , Eimeria tenella , Fluoroquinolones/therapeutic use , Poultry Diseases/drug therapy , Animals , Cecum/pathology , Coccidiosis/drug therapy , Feces/parasitology , Nitriles/therapeutic use , Oocysts/drug effects , Poultry Diseases/parasitology , Triazines/therapeutic use , Weight Gain/drug effects
20.
J Infect Chemother ; 26(6): 535-539, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32081646

ABSTRACT

Lomefloxacin may be more likely than other fluoroquinolones to cause photosensitivity. However, the rate of photosensitivity is variable and a meta-analysis has yet to be performed. The aim of this meta-analysis is to compare the rate of photosensitivity between outpatients who received lomefloxacin and those who received other fluoroquinolones. PubMed, EMBASE, Cochrane Library databases and trial registries were searched for randomized controlled trials (RCTs) of outpatients through June 12, 2019. The study outcome was the rate of photosensitivity based on the intention-to-treat principle, estimated by risk difference (RD) as the primary analysis and Peto odds ratio (Peto OR) as the secondary analysis, with 95% confidence intervals (CIs) using random-effects models. Four RCTs (total of 2295 patients) were included in this meta-analysis. A statistically higher risk of photosensitivity was found with lomefloxacin than with other fluoroquinolones (RD, 3.4%; 95% CI, 0.7%-6.2%; P-value = 0.013; I2 = 10.9%). The odds of photosensitivity was also significantly higher with lomefloxacin (Peto OR, 5.81; 95% CI, 3.34 to 10.11; P-value <0.001; I2 = 0%). This meta-analysis of RCTs found significantly higher photosensitivity with lomefloxacin compared to other fluoroquinolones. Considering this finding and given its lack of additional efficacy compared to other fluoroquinolones, lomefloxacin as a fluoroquinolone option should potentially be reconsidered.


Subject(s)
Anti-Bacterial Agents/adverse effects , Fluoroquinolones/adverse effects , Photosensitivity Disorders/chemically induced , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Female , Fluoroquinolones/administration & dosage , Humans , Male , Middle Aged , Outpatients/statistics & numerical data , Randomized Controlled Trials as Topic
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