Inhibition of rabbit renal ornithine decarboxylase activity by lead

Ornithine decarboxylase (ODC) is the first and the rate-limiting enzyme in polyamine biosynthesis. Polyamines play key roles in cell proliferation, re nal membrane transportation, and plasma membrane calcium fluxes. As part of a multidisciplinary research project to evaluate the application of the ra bbit as a relevant model for male reproductive toxicology, the effect of bl ood lead on rabbit renal ODC activity was investigated. Kidneys from rabbit s with experimentally established total blood lead concentrations of 0, 20, 40 and 80 mu g/dL and maintained at these concentrations for 10 weeks were removed at sacrifice and assayed for ODC activity. ODC activity of rabbit kidney decreased as blood lead concentration increased in a dose-dependent manner Direct addition of lead to ODC assay mixture did not alter ODC activ ity. At the blood lead concentrations examined, body weights of each group increased constantly throughout the study period. Overt lead toxicity was n ot present among the rabbits during the exposure period. The ratio of rabbi t kidney to total body weight did not show a significant difference as the blood lead concentration increased. It is possible that the major pathologi cal lesion of the rabbit kidney with subchronic lead exposure at target blo od lead concentrations (20-80 mu g/dL) is characterized by very subtle rena l tubular degeneration, though this requires further validation. The result s also demonstrated an apparent selective inhibition of lead on form A ODC activity when renal multiform ODC activities derived from control rabbits a re compared with those of rabbits maintained at a 40 mu g/dL blood lead con centration. It was recently reported that increasing blood concentrations o f lead, even within a range considered Lour, impaired kidney function in ad ult men. Rabbits and humans share many similarities in the Luminal Lead loa d of renal tubular cells in lead intoxication. Investigation of the kidney ODC profile in lead-exposed rabbits can be useful to further characterize t he mechanism of lead nephrotoxicity in humans.