scholarly journals Silver(I) Complexes of the Pharmaceutical Agents Metronidazole and 4-Hydroxymethylpyridine: Comparison of Cytotoxic Profile for Potential Clinical Application

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1949 ◽  
Author(s):  
Lidia Radko ◽  
Sylwia Stypuła-Trębas ◽  
Andrzej Posyniak ◽  
Dominik Żyro ◽  
Justyn Ochocki
Keyword(s):  
Silver Nitrate ◽  
Clinical Application ◽  
Hepg2 Cells ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Cellular Membrane ◽  
Water Soluble ◽  
Total Protein Content ◽  
Silver Complexes ◽  
Potential Clinical Application

In previous papers, we have reported on the high antifungal and significant antibacterial activity against Gram-positive and Gram-negative bacteria of the water-soluble silver(I) complexes of metronidazole and derivatives of pyridine compared to silver nitrate. In the present study, the cytotoxic activity of the silver(I) complexes of metronidazole and 4-hydroxymethylpyridine was compared with that of silver nitrate. Metronidazole and 4-hydroxymethylpyridine were investigated using Balb/c 3T3 and HepG2 cell lines in order to evaluate the potential clinical application of silver(I) complexes. The cells were exposed for 72 h to compounds at eight concentrations. The cytotoxic concentrations (IC50) of the study compounds were assessed within four biochemical endpoints: mitochondrial activity, lysosomal activity, cellular membrane integrity, and total protein content. The investigated silver(I) complexes displayed comparable cytotoxicity to that of silver nitrate used in clinics. Mean cytotoxic concentrations calculated for investigated silver(I) complexes from concentration–response curves ranged from 2.13 to 26.5 µM. HepG2 cells were less sensitive to the tested complexes compared to fibroblasts (Balb/c 3T3). However, the most affected endpoint for HepG2 cells was cellular membrane damage. The cytotoxicity of both silver complexes was comparable for Balb/c 3T3 cells. The cytotoxic potential of the new silver(I) compounds compared to that of silver nitrate used in medicine indicates that they are safe and could be used in clinical practice. The presented results are yet more stimulating to further studies that evaluate the therapeutic use of silver complexes.

scholarly journals Synthesis, Spectroscopy, Light Stability, Single-Crystal Analysis, and In Vitro Cytotoxic Activity on HepG2 Liver Cancer of Two Novel Silver(I) Complexes of Miconazole

2020 ◽  
Vol 21 (10) ◽  
pp. 3629
Author(s):  
Karolina Stryjska ◽  
Lidia Radko ◽  
Lilianna Chęcińska ◽  
Joachim Kusz ◽  
Andrzej Posyniak ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Free Ligand ◽  
Cellular Membrane ◽  
Biologically Active ◽  
Total Protein Content ◽  
Mitochondrial Activity ◽  
Cytotoxic Activities

Two novel silver(I) complexes of the biologically active ligand miconazole in the form of Ag(MCZ)2X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole]; X = NO3− (1), ClO4− (2)) were synthesized and fully characterized. The complexes were obtained by reactions of Ag(I) salts with miconazole (MCZ). Silver(I) complexes were characterized by elemental analysis, 1H-NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry, and X-ray-crystallography. This work also presents a cytotoxicity study of the silver(I) complexes of miconazole and appropriate silver(I) salts using Balb/c 3T3 and HepG2 cell lines. The cytotoxicity of the compounds was assessed based on four biochemical endpoints: lysosomal activity (neutral red uptake (NRU) assay), mitochondrial activity (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay), total protein content (TPC assay), and cellular membrane integrity (lactate dehydrogenase (LDH) assay). The cancer HepG2 cells were more sensitive to the complexes tested, and the most affected endpoint was cellular membrane damage compared to Balb/c 3T3 fibroblasts. Moreover, study complexes inhibited the growth of cancer cells at submicromolecular concentrations (0.26–0.47 μM) lower than that required for the anticancer agent, cisplatin, in MTT, NRU, and TPC assays. Both complexes were characterized by higher toxicity to human cancer cells (HepG2) than silver(I) salts and the free ligand. Combination of Ag(I) salts with miconazole is associated with the marked improvement of cytotoxic activities that can be considered as the significant point in the construction of a new generation of antineoplastic agents.

Effects of benzene, a water soluble component of crude oils, on membrane integrity and ionic content of the green alga Ankistrodesmus falcatus var. mirabilis

1978 ◽  
Vol 13 (1) ◽  
pp. 85-95 ◽  
Author(s):  
P. B. Kauss ◽  
T. C. Hutchinson
Keyword(s):  
Cell Membrane ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Water Soluble ◽  
Membrane Disruption ◽  
Time Intervals ◽  
Ionic Content ◽  
Cell Membrane Damage ◽  
Ankistrodesmus Falcatus ◽  
Cell Membrane Disruption

Abstract Experiments were devised to investigate the effects of the aromatic hydrocarbon benzene on the membrane integrity of the green freshwater alga Ankistrodesmus falcatus var. mirabilis. The ability of cells to retain ions (e.g. calcium, chlorine, copper, magnesium, manganese and potassium) when exposed to benzene was used as a measure of cell membrane disruption. Cells were exposed to various dosages of benzene in the light and the dark. Samples removed at pre-determined time intervals were analyzed for the above elements using neutron activation analysis. It was found that, (at dosages greater than ~24 umoles benzene per μl−1 cell volume), the rate of loss of potassium and manganese was proportional to both the benzene dosage and the time of exposure, but not affected by illumination. However, although loss of potassium and manganese from cells was complete after 24h exposure to the highest benzene dosage used (48 μmoles. μl−1) only a fraction of calcium, chlorine, copper and magnesium had been lost. This suggests a difference in the degree that these elements are bound or free in the cells, and that loss of potassium and manganese from cells is a sensitive indicator of cell membrane damage.

scholarly journals Influence of fluoroquinolones on viability of Balb/c 3T3 and HepG2 cells

2013 ◽  
Vol 57 (4) ◽  
pp. 599-606 ◽  
Author(s):  
Lidia Radko ◽  
Maria Minta ◽  
Sylwia Stypuła-Trębas
Keyword(s):  
Cell Lines ◽  
Membrane Integrity ◽  
Cellular Membrane ◽  
Neutral Red ◽  
Total Protein Content ◽  
Mitochondrial Activity ◽  
Response Curves ◽  
Lactate Dehydrogenase Release ◽  
Hepg2 Cell Lines ◽  
Hepatoma Hepg2

Abstract The cytotoxic potential of fluoroquinolones (enrofloxacin, ciprofloxacin, difloxacin, sarafloxacin, danofloxacin, norfloxacin and marbofloxacin) was investigated using mouse fibroblasts Balb/c 3T3 and human hepatoma HepG2 cell lines. The cells were exposed for 24, 48, and 72 h to drugs at eight concentrations ranged from 0.78 to 100 μg/mL. Four independent cytotoxicity assays were applied, in which various endpoints were assessed: mitochondrial activity - MTT reduction, lysosomal activity - neutral red uptake, total protein content, and cellular membrane integrity - lactate dehydrogenase release. Mean effective cytotoxic concentrations (EC50) calculated at different time points from concentration-response curves ranged from 10 to 100 μg/mL. The most affected endpoint in both cell lines was mitochondrial activity. The EC50-MTT-72 h <10 μg/mL was found for difloxacin, marbofloxacin (fibroblasts), sarafloxacin, and norfloxacin (HepG2). The data shows that cytotoxicity of the fluoroquinolones appears after longer exposure of both cell cultures to these compounds.

scholarly journals Ultrastructural Alterations of Erwinia carotovora subsp. atroseptica Caused by Treatment with Aluminum Chloride and Sodium Metabisulfite

2004 ◽  
Vol 70 (11) ◽  
pp. 6800-6808 ◽  
Author(s):  
Elian-Simplice Yaganza ◽  
Danny Rioux ◽  
Marie Simard ◽  
Joseph Arul ◽  
Russell J. Tweddell
Keyword(s):  
Plasma Membrane ◽  
Aluminum Chloride ◽  
Prolonged Exposure ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Erwinia Carotovora ◽  
Cellular Membrane ◽  
Ultrastructural Changes ◽  
Sodium Metabisulfite ◽  
High Concentration

ABSTRACT Aluminum and bisulfite salts inhibit the growth of several fungi and bacteria, and their application effectively controls potato soft rot caused by Erwinia carotovora. In an effort to understand their inhibitory action, ultrastructural changes in Erwinia carotovora subsp. atroseptica after exposure (0 to 20 min) to different concentrations (0.05, 0.1, and 0.2 M) of these salts were examined by using transmission electron microscopy. Plasma membrane integrity was evaluated by using the SYTOX Green fluorochrome that penetrates only cells with altered membranes. Bacteria exposed to all aluminum chloride concentrations, especially 0.2 M, exhibited loosening of the cell walls, cell wall rupture, cytoplasmic aggregation, and an absence of extracellular vesicles. Sodium metabisulfite caused mainly a retraction of plasma membrane and cellular voids which were more pronounced with increasing concentration. Bacterial mortality was closely associated with SYTOX stain absorption when bacteria were exposed to either a high concentration (0.2 M) of aluminum chloride or prolonged exposure (20 min) to 0.05 M aluminum chloride or to a pH of 2.5. Bacteria exposed to lower concentrations of aluminum chloride (0.05 and 0.1 M) for 10 min or less, or to metabisulfite at all concentrations, did not exhibit significant stain absorption, suggesting that no membrane damage occurred or it was too weak to allow the penetration of the stain into the cell. While mortality caused by aluminum chloride involves membrane damage and subsequent cytoplasmic aggregation, sulfite exerts its effect intracellularly; it is transported across the membrane by free diffusion of molecular SO2 with little damage to the cellular membrane.

IMPACT OF SORBITOL- INDUCED OSMOTIC STRESS ON SOME BIOCHEMICAL TRAITS OF POTATO IN VITRO

2020 ◽  
Vol 51 (4) ◽  
pp. 1038-1047
Author(s):  
Mawia & et al.
Keyword(s):  
Ascorbic Acid ◽  
Osmotic Stress ◽  
Cytoplasmic Membrane ◽  
Genotypic Variation ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Culture Collection ◽  
Nutritive Medium ◽  
Starting Point

This study had as principal objective identification of osmotic-tolerant potato genotypes by using "in vitro" tissue culture and sorbitol as a stimulating agent, to induce water stress, which was added to the  culture nutritive medium in different concentration (0,50, 110, 220, 330 and 440 mM).  The starting point was represented by plantlets culture collection, belonging to eleven potato genotypes: Barcelona, Nectar, Alison, Jelly, Malice, Nazca, Toronto, Farida, Fabulla, Colomba and Spunta. Plantlets were multiplied between two internodes to obtain microcuttings (in sterile condition), which were inoculated on medium. Sorbitol-induced osmotic stress caused a significant reduction in the ascorbic acid, while the concentration of proline, H2O2 and solutes leakage increased compared with the control. Increased the proline content prevented lipid peroxidation, which played a pivotal role in the maintenance of membrane integrity under osmotic stress conditions. The extent of the cytoplasmic membrane damage depends on osmotic stress severity and the genotypic variation in the maintenance of membranes stability was highly associated with the ability of producing more amounts of osmoprotectants (proline) and the non-enzymic antioxidant ascorbic acid in response to osmotic stress level. The results showed that the genotypes Jelly, Nectar, Allison, Toronto, and Colomba are classified as highly osmotic stress tolerant genotypes, while the genotypes Nazca and Farida are classified as osmotic stress susceptible ones.

Limitations and Potential Clinical Application on Contrast Echocardiography

2009 ◽  
Vol 999 (999) ◽  
pp. 1-7
Author(s):  
Elisa Modonesi ◽  
Manrico Balbi ◽  
Gian Paolo Bezante
Keyword(s):  
Clinical Application ◽  
Contrast Echocardiography ◽  
Potential Clinical Application

scholarly journals Plasma membrane integrity: implications for health and disease

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dustin A. Ammendolia ◽  
William M. Bement ◽  
John H. Brumell
Keyword(s):  
Plasma Membrane ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Whole Body ◽  
Plasma Membrane Integrity ◽  
Plasma Membrane Damage ◽  
Cellular Environment ◽  
Health And Disease ◽  
Repair Pathways ◽  
The Impact

AbstractPlasma membrane integrity is essential for cellular homeostasis. In vivo, cells experience plasma membrane damage from a multitude of stressors in the extra- and intra-cellular environment. To avoid lethal consequences, cells are equipped with repair pathways to restore membrane integrity. Here, we assess plasma membrane damage and repair from a whole-body perspective. We highlight the role of tissue-specific stressors in health and disease and examine membrane repair pathways across diverse cell types. Furthermore, we outline the impact of genetic and environmental factors on plasma membrane integrity and how these contribute to disease pathogenesis in different tissues.

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