In vitro toxicity in long-term cell culture of MR contrast agents targeted to cartilage evaluation
| Autor: | Gerald M. Rosen, Ronald J. Midura, Carl S. Winalski, Erika Schneider, F.A. Sakamoto, S. Midura |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cartilage
Articular Gadolinium DTPA Dendrimers Pathology medicine.medical_specialty Cytotoxicity Cell Drug Evaluation Preclinical Biomedical Engineering Contrast Media Tartrate Pharmacology Chondrocyte chemistry.chemical_compound Chondrocytes Magnetic resonance imaging Rheumatology Tumor Cells Cultured medicine Animals Staurosporine Orthopedics and Sports Medicine Cell Proliferation Dendrimer Dose-Response Relationship Drug Cell growth business.industry DNA In vitro Rats medicine.anatomical_structure Cartilage Contrast agent chemistry Cell culture Toxicity business medicine.drug |
| Zdroj: | Osteoarthritis and Cartilage. 22(9):1337-1345 |
| ISSN: | 1063-4584 |
| DOI: | 10.1016/j.joca.2014.07.010 |
| Popis: | summary Objective: Contrast-enhanced magnetic resonance (MR) imaging methods have been proposed for noninvasive evaluation of osteoarthritis (OA). We measured cell toxicities of cartilage-targeted low-generation dendrimer-linked nitroxide MR contrast agents and gadopentetate dimeglumine (Gd-DTPA) on cultured chondrocytes. Design: A long-term Swarm rat chondrosarcoma chondrocyte-like cell line was exposed for 48-h to different salts (citrate, maleate, tartrate) and concentrations of generation one or two diaminobutyllinked nitroxides (DAB4-DLN or DAB8-DLN), Gd-DTPA, or staurosporine (positive control). Impact on microscopic cell appearance, MTT spectrophotometric assays of metabolic activity, and quantitative PicoGreen assays of DNA content (cell proliferation) were measured and compared to untreated cultures. Results: Chondrocyte cultures treated with up to 7.5 mM Gd-DTPA for 48-h had no statistical differences in DNA content or MTT reaction compared to untreated cultures. At all doses, DAB4-DLN citrate treated cultures had results similar to untreated and Gd-DTPA-treated cultures. At doses >1 mM, DAB4-DLN citrate treated cultures showed statistically greater DNA and MTT reaction than maleate and tartrate DAB4-DLN salts. Cultures exposed to 5 mM or 7.5 mM DAB8-DLN citrate exhibited rounded cells, poor cell proliferation, and barely detectable MTT reaction. Treatment with 0.1 mM staurosporine caused chondrocyte death. Conclusion: Long-term exposure, greater than clinically expected, to either DAB4-DLN citrate or Gd-DTPA had no detectable toxicity with results equivalent to untreated cultures. DAB4-DLN citrate was more biocompatible than either the maleate or tartrate salts. Cells exposed for 48-h to 5 mM or 7.5 mM DAB8DLN salts demonstrated significant cell toxicity. Further evaluation of DAB8-DLN with clinically appropriate exposure times is required to determine the maximum useful concentration. |
| Databáze: | OpenAIRE |
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