Development of a primary culture system of rat kidney cortical cells to evaluate the nephrotoxicity of xenobiotics.
A method has been developed for preparing primary monolayer cultures of postnatal rat kidney cortical epithelial cells. These cultures maintained differentiated cell functions and epithelial-like morphology for several days in culture. The presence of alkaline phosphatase and maltase was used to confirm the presence of cells from the renal cortex. The concentrations of these enzymes were maintained in culture until day 3, but had declined significantly by day 5. Similar patterns were observed with cytochrome P-450 and glutathione content, although their concentrations remained stable from day 3 to day 5. Mercuric chloride, cadmium chloride and acetaminophen were evaluated for nephrotoxicity in this culture system. Treatment with these compounds resulted in dose-dependent changes in cell morphology and in biochemical parameters such as lactate dehydrogenase leakage, alkaline phosphatase activity and cellular glutathione content. With this culture system, it was possible to detect the acute toxicities of compounds that produce varying degrees of renal injury. Further development of this kidney culture system may have value in detecting potential nephrotoxins and in studying their mechanisms of toxicity.
D000082:Acetaminophen / Q000633:toxicity*; D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D019256:Cadmium Chloride; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005978:Glutathione / Q000032:analysis; D007672:Kidney Cortex / Q000187:drug effects* / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008627:Mercuric Chloride / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D000520:alpha-Glucosidases / Q000032:analysis
D002104:Cadmium; D000082:Acetaminophen; D008627:Mercuric Chloride; D003577:Cytochrome P-450 Enzyme System; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D000520:alpha-Glucosidases; D005978:Glutathione; D019256:Cadmium Chloride