Effects of 4-dimethylaminophenol in rat kidneys, isolated rat kidney tubules and hepatocytes

1. Addition of 4-dimethylaminophenol (DMAP) to suspensions of isolated rat kidney tubules increased extracellular Lactate Dehydrogenase (LDH) at concn. which did not markedly affect gluconeogenesis. ATP content was also decreased by DMAP but this did not occur until the membrane became permeable to LDH. There was no similar leakage of the mitochondrial Enzyme glutamate dehydrogenase. 2. After i.v. injection of DMAP to rats in doses which did not inhibit gluconeogenesis, kidney glutathione was decreased and the urinary LDH was increased. DMAP was irreversibly bound to tissue in rat, with the highest binding in the kidney. The highest binding occurs in those tissues in which DMAP causes necrosis. 3. In isolated rat hepatocytes, DMAP caused toxic effects which were similar but less extensive than occur on addition of DMAP to kidney tubules. The formation of acid-soluble metabolites was higher in isolated rat hepatocytes (20 nmol/mg protein) than in rat kidney tubules (4 nmol/mg protein). DMAP-glucuronide and DMAP-sulphate comprised the major acid-soluble metabolites in both preparations; conjugates of DMAP with glutathione or cysteine were also found.