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Cytotoxicity and membrane damage in vitro by inclusion complexes between gamma-cyclodextrin and siloxanes. Curr Top Microbiol Immunol 1996;210:93-9

Date

01/01/1996

Pubmed ID

8565593

DOI

10.1007/978-3-642-85226-8_10

Scopus ID

2-s2.0-0030025029   6 Citations

Abstract

Inclusion complexes of gamma-cyclodextrin and octamethylcyclotetrasiloxane (D4), decamethyltetrasiloxane (M10TS), and 1,3,5,7-tetramethyltetravinylcyclotetra - siloxane (TMTV-D4) were prepared to compare the cytotoxic effects of siloxanes in vitro. In these preparations, the hydrophobic siloxanes are surrounded by a hydrophilic shell of eight circularly linked D-glucose molecules (gamma-cyclodextrin), and upon contact with plasma membranes the siloxane molecule can intercalate into the lipid bilayer of the cell membrane. XRPC24, 2-11 plasmacytoma, CH12.LX lymphoma and P388D1 macrophage-like cells were used as indicator cells in toxicity assays. Using an MTT tetrazolium reduction to formazan test, a colorimetric method to determine the number of viable cells, the 50% minimal lethal doses (CD50) for the siloxane compounds were found to range from 30 to 50 microM. Sublethal doses (e.g., 15 microM and lower) resulted in the loss of lactate dehydrogenase (LDH) and glutathione (GSH) from the cytosolic compartment of the target cells and thus indicated cytotoxicity. Treatment of macrophages with siloxanes resulted in a higher production of interleukin-6 (IL-6) than was exhibited by untreated macrophages. The B9 cell bioassay of these treated cells showed as much as a 10 fold higher production (500 U/ml) of IL-6 than did the untreated cells. The degree of increase was dependent on the compound and concentration used. The results of this study show that low molecular weight siloxanes produce lethal effects on B-lymphocyte derived target cells in vitro and permeabilize the plasma membranes at lower sublethal concentrations.

Author List

Felix K, Janz S, Pitha J, Williams JA, Mushinski EB, Bornkamm GW, Potter M

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Survival
Cells, Cultured
Cyclodextrins
Interleukin-6
Mice
Siloxanes
gamma-Cyclodextrins