Pharmacologic modification of the cytotoxic effects of cadmium in LLC-PK sub 1 cells

Journal Article · Thu Feb 09 04:00:00 EST 1989 · FASEB Journal (Federation of American Societies for Experimental Biology); (USA)

OSTI ID:6929527

Battaglia, D R; Kahan, B S; Niewenhuis, R J; Prozialeck, W C ^[1]

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1. 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), Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (USA) Vol. 3:3; ISSN FAJOE; ISSN 0892-6638
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
CADMIUM
CADMIUM CHLORIDES
CADMIUM COMPOUNDS
CADMIUM HALIDES
CHLORIDES
CHLORINE COMPOUNDS
COMPARATIVE EVALUATIONS
DOMESTIC ANIMALS
DRUGS
ELEMENTS
HALIDES
HALOGEN COMPOUNDS
MAMMALS
METALS
MORPHOLOGICAL CHANGES
SWINE
TOXICITY
VERTEBRATES