Pharmacologic modification of the cytotoxic effects of cadmium in LLC-PK sub 1 cells
- Philadelphia College of Osteopathic Medicine, PA (USA)
Recent results from our laboratories have shown that exposure to cadmium causes LLC-PK{sub 1} cells to shrink, detach and assume a spherical shape. The purpose of the present studies was to determine whether various pharmacologic agents can reduce or prevent these cytotoxic effects of Cd{sup 2+}. Confluent monolayers of LLC-PK{sub 1} cells were incubated with the drugs of interest (50 microM final concentration) for 2 hours. CadCl{sub 2} (final concentration = 75 microM) was then added and the cells were incubated for another 20 hours. Morphologic changes were assessed qualitatively by viewing the cells with a phase contrast microscope. The extent of Cd{sup 2+}-induced cellular damage was also quantified by staining the cells that remained on the growing surface with methylene blue, solubilizing the stained cells, and determining the absorbance at 660 nm. The results showed that several drugs, particularly the calmodulin antagonists trifluoperazine chlorpromazine, and the calcium channel blocker verapamil, significant reduced the severity of Cd{sup 2+}-induced cytotoxicity. By contrast, a variety of other agents, such as chlorpromazine sulfoxide, trifluoperazine sulfoxide, phenytoin and zinc, had no such protective effect. These findings indicate that Ca{sup 2+} antagonists can attenuate the cytotoxic effects of Cd{sup 2+} and that Cd{sup 2+} may produce some of its effects by activating Ca{sup 2+} -dependent systems.
- OSTI ID:
- 6929527
- Journal Information:
- FASEB Journal (Federation of American Societies for Experimental Biology); (USA), Vol. 3:3; ISSN 0892-6638
- Country of Publication:
- United States
- Language:
- English
Similar Records
Volume regulation by human lymphocytes. Role of calcium
Role of the sodium-dependent phosphate co-transporters and of the phosphate complexes of uranyl in the cytotoxicity of uranium in LLC-PK{sub 1} cells
Related Subjects
ANIMAL CELLS
MORPHOLOGICAL CHANGES
CADMIUM
TOXICITY
DRUGS
BIOLOGICAL EFFECTS
CADMIUM CHLORIDES
COMPARATIVE EVALUATIONS
SWINE
ANIMALS
CADMIUM COMPOUNDS
CADMIUM HALIDES
CHLORIDES
CHLORINE COMPOUNDS
DOMESTIC ANIMALS
ELEMENTS
HALIDES
HALOGEN COMPOUNDS
MAMMALS
METALS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology