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. 1997 Jun;54(6):432–436. doi: 10.1136/oem.54.6.432

Urinary neutral endopeptidase in workers exposed to cadmium: interaction with cigarette smoking.

J Nortier 1, A Bernard 1, H Roels 1, M Deschodt-Lanckman 1, C Gueuning 1, R Lauwerys 1
PMCID: PMC1128804  PMID: 9245950

Abstract

OBJECTIVES: Structural impairment of the renal proximal tubular epithelium induced by cadmium (Cd) was investigated by measuring the concentration of neutral endopeptidase 24.11 (NEP), an ectoenzyme of the apical brush border, in the urine of 106 male workers employed in a Cd smelter (among whom 52 were occupationally exposed to Cd), and by comparing it with other tubular markers (low molecular weight proteins, lysosomal enzymes). METHODS: NEP (EC 3.4.24.11), beta-N-acetyl-glucosaminidase (NAG) (EC 3.2.1.30), and NAG-B isoenzyme activities were measured by fluorimetric assays, whereas the concentrations of retinol binding protein (RBP), beta 2-microglobulin (beta 2M), and Clara cell protein (CC16) were measured by automated latex agglutination techniques. RESULTS: An increased urinary excretion of NEP as well as microproteins was found only in subjects excreting more than 5 micrograms Cd/g creatinine. In this group, NEP concentrations were significantly higher in the subjects who smoked. This significant interaction could not be found for any other marker tested. CONCLUSIONS: The data suggest that NEP enzymuria is high even at low exposures to Cd (with a threshold of urinary cadmium excretion (U-Cd) at 5 micrograms/g creatinine), indicating early structural alterations. Moreover, its particular sensitivity to smoking could be useful in the detection of new population clusters potentially more susceptible to development of nephrotoxic insult.

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Selected References

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  1. Bernard A. M., Lauwerys R. R. Continuous-flow system for automation of latex immunoassay by particle counting. Clin Chem. 1983 Jun;29(6):1007–1011. [PubMed] [Google Scholar]
  2. Bernard A., Roels H., Buchet J. P., Cardenas A., Lauwerys R. Cadmium and health: the Belgian experience. IARC Sci Publ. 1992;(118):15–33. [PubMed] [Google Scholar]
  3. Bernard A., Thielemans N., Roels H., Lauwerys R. Association between NAG-B and cadmium in urine with no evidence of a threshold. Occup Environ Med. 1995 Mar;52(3):177–180. doi: 10.1136/oem.52.3.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cockcroft D. W., Gault M. H. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. doi: 10.1159/000180580. [DOI] [PubMed] [Google Scholar]
  5. Deschodt-Lanckman M., Michaux F., De Prez E., Abramowicz D., Vanherweghem J. L., Goldman M. Increased serum levels of endopeptidase 24.11 ('enkephalinase') in patients with end-stage renal failure. Life Sci. 1989;45(2):133–141. doi: 10.1016/0024-3205(89)90287-7. [DOI] [PubMed] [Google Scholar]
  6. Fels L. M., Bundschuh I., Gwinner W., Jung K., Pergande M., Graubaum H. J., Price R. G., Taylor S. A., De Broe M. E., Nuyts G. D. Early urinary markers of target nephron segments as studied in cadmium toxicity. Kidney Int Suppl. 1994 Nov;47:S81–S88. [PubMed] [Google Scholar]
  7. Kellerman P. S., Clark R. A., Hoilien C. A., Linas S. L., Molitoris B. A. Role of microfilaments in maintenance of proximal tubule structural and functional integrity. Am J Physiol. 1990 Aug;259(2 Pt 2):F279–F285. doi: 10.1152/ajprenal.1990.259.2.F279. [DOI] [PubMed] [Google Scholar]
  8. Kimura O., Endo T., Sakata M. Comparison of cadmium uptakes from apical and basolateral membranes of LLC-PK1 cells. Toxicol Appl Pharmacol. 1996 Apr;137(2):301–306. doi: 10.1006/taap.1996.0084. [DOI] [PubMed] [Google Scholar]
  9. Lauwerys R. R., Bernard A. M., Roels H. A., Buchet J. P. Cadmium: exposure markers as predictors of nephrotoxic effects. Clin Chem. 1994 Jul;40(7 Pt 2):1391–1394. [PubMed] [Google Scholar]
  10. Nortier J., Abramowicz D., Kinnaert P., Deschodt-Lanckman M., Vanherweghem J. L. Pathological release of urinary endopeptidase 24.11 early after renal transplantation. Enzyme. 1992;46(6):304–308. doi: 10.1159/000468808. [DOI] [PubMed] [Google Scholar]
  11. Nouwen E. J., De Broe M. E. Human intestinal versus tissue-nonspecific alkaline phosphatase as complementary urinary markers for the proximal tubule. Kidney Int Suppl. 1994 Nov;47:S43–S51. [PubMed] [Google Scholar]
  12. Prozialeck W. C., Lamar P. C. Effects of glutathione depletion on the cytotoxic actions of cadmium in LLC-PK1 cells. Toxicol Appl Pharmacol. 1995 Oct;134(2):285–295. doi: 10.1006/taap.1995.1194. [DOI] [PubMed] [Google Scholar]
  13. Prozialeck W. C., Niewenhuis R. J. Cadmium (Cd2+) disrupts intercellular junctions and actin filaments in LLC-PK1 cells. Toxicol Appl Pharmacol. 1991 Jan;107(1):81–97. doi: 10.1016/0041-008x(91)90333-a. [DOI] [PubMed] [Google Scholar]
  14. Reed D. J. Glutathione: toxicological implications. Annu Rev Pharmacol Toxicol. 1990;30:603–631. doi: 10.1146/annurev.pa.30.040190.003131. [DOI] [PubMed] [Google Scholar]
  15. Roels H. A., Lauwerys R. R., Buchet J. P., Bernard A. M., Vos A., Oversteyns M. Health significance of cadmium induced renal dysfunction: a five year follow up. Br J Ind Med. 1989 Nov;46(11):755–764. doi: 10.1136/oem.46.11.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Roels H., Bernard A. M., Cárdenas A., Buchet J. P., Lauwerys R. R., Hotter G., Ramis I., Mutti A., Franchini I., Bundschuh I. Markers of early renal changes induced by industrial pollutants. III. Application to workers exposed to cadmium. Br J Ind Med. 1993 Jan;50(1):37–48. doi: 10.1136/oem.50.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ronco P., Pollard H., Galceran M., Delauche M., Schwartz J. C., Verroust P. Distribution of enkephalinase (membrane metalloendopeptidase, E.C. 3.4.24.11) in rat organs. Detection using a monoclonal antibody. Lab Invest. 1988 Feb;58(2):210–217. [PubMed] [Google Scholar]
  18. Roques B. P., Noble F., Daugé V., Fournié-Zaluski M. C., Beaumont A. Neutral endopeptidase 24.11: structure, inhibition, and experimental and clinical pharmacology. Pharmacol Rev. 1993 Mar;45(1):87–146. [PubMed] [Google Scholar]
  19. Schulz W. W., Hagler H. K., Buja L. M., Erdös E. G. Ultrastructural localization of angiotensin I-converting enzyme (EC 3.4.15.1) and neutral metalloendopeptidase (EC 3.4.24.11) in the proximal tubule of the human kidney. Lab Invest. 1988 Dec;59(6):789–797. [PubMed] [Google Scholar]
  20. Shipp M. A., Look A. T. Hematopoietic differentiation antigens that are membrane-associated enzymes: cutting is the key! Blood. 1993 Aug 15;82(4):1052–1070. [PubMed] [Google Scholar]
  21. Sidhu M., Sharma M., Bhatia M., Awasthi Y. C., Nath R. Effect of chronic cadmium exposure on glutathione S-transferase and glutathione peroxidase activities in rhesus monkey: the role of selenium. Toxicology. 1993 Oct 25;83(1-3):203–213. doi: 10.1016/0300-483x(93)90102-x. [DOI] [PubMed] [Google Scholar]
  22. Splittgerber A. G., Tappel A. L. Inhibition of glutathione peroxidase by cadmium and other metal ions. Arch Biochem Biophys. 1979 Oct 15;197(2):534–542. doi: 10.1016/0003-9861(79)90277-7. [DOI] [PubMed] [Google Scholar]
  23. Staessen J. A., Lauwerys R. R., Ide G., Roels H. A., Vyncke G., Amery A. Renal function and historical environmental cadmium pollution from zinc smelters. Lancet. 1994 Jun 18;343(8912):1523–1527. doi: 10.1016/s0140-6736(94)92936-x. [DOI] [PubMed] [Google Scholar]
  24. Tucker S. M., Boyd P. J., Thompson A. E., Price R. G. Automated assay of N-acetyl-beta-glucosaminidase in normal and pathological human urine. Clin Chim Acta. 1975 Jul 23;62(2):333–339. doi: 10.1016/0009-8981(75)90245-4. [DOI] [PubMed] [Google Scholar]

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