scholarly journals Ex vivo toxicological evaluation of experimental anticancer gold(i) complexes with lansoprazole-type ligands

2019 ◽  
Vol 8 (6) ◽  
pp. 885-895
Author(s):  
Natalia Estrada-Ortiz ◽  
Elena Lopez-Gonzales ◽  
Ben Woods ◽  
Stefan Stürup ◽  
Inge A. M. de Graaf ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Ex Vivo ◽  
Gold Complex ◽  
Ex Vivo Model ◽  
Toxicological Evaluation ◽  
Anticancer Compounds ◽  
Kidney Slices ◽  
Icp Ms ◽  
Gold Compounds ◽  
Liver And Kidney

Abstract Gold-based compounds are of great interest in the field of medicinal chemistry as novel therapeutic (anticancer) agents due to their peculiar reactivity and mechanisms of action with respect to organic drugs. Despite their promising pharmacological properties, the possible toxic effects of gold compounds need to be carefully evaluated in order to optimize their design and applicability. This study reports on the potential toxicity of three experimental gold-based anticancer compounds featuring lansoprazole ligands (1–3) studied in an ex vivo model, using rat precision cut kidney and liver slices (PCKS and PCLS, respectively). The results showed a different toxicity profile for the tested compounds, with the neutral complex 2 being the least toxic, even less toxic than cisplatin, followed by the cationic complex 1. The dinuclear cationic gold complex 3 was the most toxic in both liver and kidney slices. This result correlated with the metal uptake of the different compounds assessed by ICP-MS, where complex 3 showed the highest accumulation of gold in liver and kidney slices. Interestingly compound 1 showed the highest selectivity towards cancer cells compared to the healthy tissues. Histomorphology evaluation showed a similar pattern for all three Au(i) complexes, where the distal tubular cells suffered the most extensive damage, in contrast to the damage in the proximal tubules induced by cisplatin. The binding of representative gold compounds with the model ubiquitin was also studied by ESI-MS, showing that after 24 h incubation only ‘naked’ Au ions were bound to the protein following ligands’ loss. The mRNA expression of stress response genes appeared to be similar for both evaluated organs, suggesting oxidative stress as the possible mechanism of toxicity. The obtained results open new perspectives towards the design and testing of bifunctional gold complexes with chemotherapeutic applications.

1849: Systematic Evaluation of 21μm Thulium Laser Device for Treatment of Benign Prostatic Enlargement in an Ex-VIVO Model

2007 ◽  
Vol 177 (4S) ◽  
pp. 614-614 ◽  
Author(s):  
Gunnar Wendt-Nordahl ◽  
Stefanie Huckele ◽  
Patrick Honeck ◽  
Peter Aiken ◽  
Thomas Knoll ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Systematic Evaluation ◽  
Thulium Laser ◽  
Laser Device ◽  
Benign Prostatic Enlargement ◽  
Ex Vivo Model ◽  
Prostatic Enlargement

Porcine small intestine, a good ex vivo model to investigate absorption and metabolism of natural products

2017 ◽  
Author(s):  
J Houriet ◽  
YE Arnold ◽  
C Petit ◽  
YN Kalia ◽  
JL Wolfender
Keyword(s):  
Natural Products ◽  
Small Intestine ◽  
Ex Vivo ◽  
Ex Vivo Model

Effects of Two Different Doses of Hirudin on APTT, Determined with Eight Different Reagents

1995 ◽  
Vol 73 (02) ◽  
pp. 219-222 ◽  
Author(s):  
Manuel Monreal ◽  
Luis Monreal ◽  
Rafael Ruiz de Gopegui ◽  
Yvonne Espada ◽  
Ana Maria Angles ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
In Vitro Study ◽  
Ex Vivo Model ◽  
Suitable Candidate ◽  
Significant Prolongation ◽  
High Doses ◽  
Different Doses

SummaryThe APTT has been considered the most suitable candidate to monitor the anticoagulant activity of hirudin. However, its use is hampered by problems of standardization, which make the results heavily dependent on the responsiveness of the reagent used. Our aim was to investigate if this different responsiveness of different reagents when added in vitro is to be confirmed in an ex vivo study.Two different doses of r-hirudin (CGP 39393), 0.3 mg/kg and 1 mg/kg, were administered subcutaneously to 20 New Zealand male rabbits, and the differences in prolongation of APTT 2 and 12 h later were compared, using 8 widely used commercial reagents. All groups exhibited a significant prolongation of APTT 2 h after sc administration of hirudin, both at low and high doses. But this prolongation persisted 12 h later only when the PTTa reagent (Boehringer Mannheim) was used. In general, hirudin prolonged the APTT most with the silica- based reagents.In a further study, we compared the same APTT reagents in an in vitro study in which normal pooled plasma was mixed with increasing amount of hirudin. We failed to confirm a higher sensitivity for silica- containing reagents. Thus, we conclude that subcutaneous administration of hirudin prolongs the APTT most with the silica-based reagents, but this effect is exclusive for the ex vivo model.

EMR+: Vorstellung einer neuen endoskopischen Resektionsmethode im ex-vivo Model

2019 ◽  
Author(s):  
RF Knoop ◽  
E Wedi ◽  
V Ellenrieder ◽  
A Neesse ◽  
S Kunsch
Keyword(s):  
Ex Vivo ◽  
Ex Vivo Model

Anti-Inflammatory Effects of Novel Standardized Platelet Rich Plasma Releasates on Knee Osteoarthritic Chondrocytes and Cartilage in vitro

2019 ◽  
Vol 20 (11) ◽  
pp. 920-933 ◽  
Author(s):  
Lucía Gato-Calvo ◽  
Tamara Hermida-Gómez ◽  
Cristina R. Romero ◽  
Elena F. Burguera ◽  
Francisco J. Blanco
Keyword(s):  
Gene Expression ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Cartilage Explants ◽  
Ex Vivo Model ◽  
Chondrocyte Viability ◽  
Platelet Concentration ◽  
The Absolute ◽  
Anti Inflammatory

Background: Platelet Rich Plasma (PRP) has recently emerged as a potential treatment for osteoarthritis (OA), but composition heterogeneity hampers comparison among studies, with the result that definite conclusions on its efficacy have not been reached. Objective: 1) To develop a novel methodology to prepare a series of standardized PRP releasates (PRP-Rs) with known absolute platelet concentrations, and 2) To evaluate the influence of this standardization parameter on the anti-inflammatory properties of these PRP-Rs in an in vitro and an ex vivo model of OA. Methods: A series of PRPs was prepared using the absolute platelet concentration as the standardization parameter. Doses of platelets ranged from 0% (platelet poor plasma, PPP) to 1.5·105 platelets/µl. PRPs were then activated with CaCl2 to obtain releasates (PRP-R). Chondrocytes were stimulated with 10% of each PRP-R in serum-free culture medium for 72 h to assess proliferation and viability. Cells were co-stimulated with interleukin (IL)-1β (5 ng/ml) and 10% of each PRP-R for 48 h to determine the effects on gene expression, secretion and intra-cellular content of common markers associated with inflammation, catabolism and oxidative stress in OA. OA cartilage explants were co-stimulated with IL-1β (5 ng/ml) and 10% of either PRP-R with 0.75·105 platelets/µl or PRP-R with 1.5·105 platelets/µl for 21 days to assess matrix inflammatory degradation. Results: Chondrocyte viability was not affected, and proliferation was dose-dependently increased. The gene expression of all pro-inflammatory mediators was significantly and dose-independently reduced, except for that of IL-1β and IL-8. Immunoblotting corroborated this effect for inducible NO synthase (NOS2). Secreted matrix metalloproteinase-13 (MMP-13) was reduced to almost basal levels by the PRP-R from PPP. Increasing platelet dosage led to progressive loss to this anti-catabolic ability. Safranin O and toluidine blue stains supported the beneficial effect of low platelet dosage on cartilage matrix preservation. Conclusion: We have developed a methodology to prepare PRP releasates using the absolute platelet concentration as the standardization parameter. Using this approach, the composition of the resulting PRP derived product is independent of the donor initial basal platelet count, thereby allowing the evaluation of its effects objectively and reproducibly. In our OA models, PRP-Rs showed antiinflammatory, anti-oxidant and anti-catabolic properties. Platelet enrichment could favor chondrocyte proliferation but is not necessary for the above effects and could even be counter-productive.

Cytotoxic Activity and DNA Binding Property of New Aminopyrimidine Derivatives

2020 ◽  
Vol 17 (5) ◽  
pp. 640-654
Author(s):  
Hamidreza Akrami ◽  
Bibi Fatemeh Mirjalili ◽  
Omidreza Firuzi ◽  
Azadeh Hekmat ◽  
Ali Akbar Saboury ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Lymphoblastic Leukemia ◽  
Cd Spectroscopy ◽  
Myelogenous Leukemia ◽  
Breast Adenocarcinoma ◽  
Binding Property ◽  
Anticancer Compounds ◽  
Calf Thymus ◽  
Dna Binding Property

Background: Chromene and anilinopyrimidine heterocyclics are attractive anticancer compounds that have inspired many researchers to design novel derivatives bearing improved anticancer activity. Methods: A series of pyrimidine-fused benzo[f]chromene derivatives 6a-x were synthesized as anticancer hybrids of 1H-benzo[f]chromenes and anilinopyrimidines. The inhibitory activity of the synthesized compounds 6a-x against cell viability of human chronic myelogenous leukemia (K562), human acute lymphoblastic leukemia (MOLT-4) and human breast adenocarcinoma (MCF-7) cell lines was evaluated using MTT assay. The interaction of the most promising compound with calf-thymus DNA was also studied using spectrometric titrations and Circular Dichroism (CD) spectroscopy. Results: Most compounds showed promising activity against tested cell lines. Among them, 2,4- dimethoxyanilino derivative 6g exhibited the best profile of activity against tested cell lines (IC50s = 1.6-6.1 μM) with no toxicity against NIH3T3 normal cell (IC50 >200 μM). The spectrometric studies exhibited that compound 6g binds to DNA strongly and may change DNA conformation significantly, presumably via a groove binding mechanism. Conclusion: The results of this study suggest that the prototype compound 6g can be considered as a novel lead compound for the design and discovery of novel anticancer agents.

scholarly journals Anti-pseudomonad Activity of Manuka Honey and Antibiotics in a Specialized ex vivo Model Simulating Cystic Fibrosis Lung Infection

2019 ◽  
Vol 10 ◽  
Author(s):  
Aled E. L. Roberts ◽  
Lydia C. Powell ◽  
Manon F. Pritchard ◽  
David W. Thomas ◽  
Rowena E. Jenkins
Keyword(s):  
Cystic Fibrosis ◽  
Ex Vivo ◽  
Lung Infection ◽  
Cystic Fibrosis Lung ◽  
Manuka Honey ◽  
Ex Vivo Model
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