In vitro toxicity of antibiotics to LLC-RK(1) rabbit kidney cells.
The renal toxicity of cephalosporin and aminoglycoside antibiotics has been studied in an in vitro system using the rabbit kidney cell line LLC-RK(1). The effect of a rabbit kidney S-9 metabolizing system on the toxicity the antibiotics was also studied. Cultures of the LLC-RK(1) cells were established in microtitre plates and exposed to test compounds in the concentration range 0 to 2000 mug/ml, either in the presence or absence of an S-9 metabolizing system. The compounds were in contact with the cultures for a period of 48 hr before viability of the cells was determined. Assay of cell viability was based on the mitochondrial conversion of 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide to a coloured formazan product (MTT Assay). Duplicate cultures were also tested with a neutral red staining assay. Cephalosporins tested were cephaloridine, cephalothin, cephapirin, cefotaxime, ceftazidime, cephaloglycin, cefoperazone and cefazolin. The aminoglycoside antibiotics tested were gentamicin, neomycin and kanamycin. A good correlation was seen between in vitro toxicity and in vivo effects for these compounds. Further techniques were investigated to assess sub-cytolethal impairment of renal function in the LLC-RK(1) cells. Both in vivo clearance studies and in vitro kidney slice methods have used transport of the organic ions tetraethyl ammonium and p-aminohippurate as indices of renal function. Therefore the ability of LLC-RK(1) cells to transport these ions was investigated. Where ion transport was demonstrated the effect of nephrotoxic antibiotics on this kidney function was studied.
Duffy
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Cellular and Experimental Toxicology, Safety of Medicines, ICI Pharmaceuticals, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TJ, England.
McNae
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