The mechanisms of target cell injury by nephrotoxins.
Hexachlorobutadiene-N-acetylcysteine (HCBD-NAC), adriamycin and 2-bromoethanamine hydrobromide are three renal toxins that have shown in vivo a highly selective target cell toxicity--to the proximal tubules, the glomerular epithelial cells and the medullary interstitial cells, respectively. To study some aspects of the mechanisms of this selective toxicity, the three types of target cell were isolated from the kidneys of Wistar rats, and cultures of the cells or tissue fragments were exposed to various concentrations of the three toxins. Using fluorescence microscopy combined with enzyme and histochemical probes, the selective target-cell toxicity of the three compounds already established in vivo was demonstrated also in vitro. Moreover, the in vitro toxic effect of HCBD-NAC was ameliorated by probenecid, as is the case in vivo. Several functional characteristics specific to each of the target cells, such as the selective uptake of a toxin, the presence of lipid droplets and the level of peroxidative enzyme activity, have been identified as probable factors in the occurrence of the target cell necrosis.
D000111:Acetylcysteine / Q000031:analogs & derivatives*; D000818:Animals; D002070:Butadienes / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives* / Q000633:toxicity; D004317:Doxorubicin / Q000633:toxicity*; D005021:Ethylamines / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008055:Lipids / Q000032:analysis; D008297:Male; D010544:Peroxidases / Q000032:analysis; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002070:Butadienes; D005021:Ethylamines; D008055:Lipids; C004504:2-bromoethylamine; D004317:Doxorubicin; C049739:N-acetyl-S-pentachloro-1,3-butadienylcysteine; D010544:Peroxidases; D003545:Cysteine; D011339:Probenecid; D000111:Acetylcysteine