EFFECTS OF LEAD AND MANGANESE ON THE RELEASE OF LYSOSOMAL-ENZYMES IN-VITRO AND IN-VIVO

In this study we evaluated the effects of two heavy metals, lead and m anganese, on the release of some glycohydrolases of lysosomal origin, N-acetyl-beta-D-olucosaminidase and its major isoenzymes, beta-D-glucu ronidase and alpha-D-galactosidase, We have studied release of these e nzymes in vitro from peripheral mitogen-activated lymphocytes from hea lthy subjects after addition of Pb or Mn to the medium and their plasm a levels in individuals exposed at work to Pb (31 subjects) or to mang anese (36 subjects), versus matched controls. We also determined the p lasma levels in a general population (417 subjects). The enzymatic act ivities were assayed fluorimetrically with 4-methylumbelliferyl-glycos ides as substrates. Particular attention was given to some technical a spects: enzymatic activity was preserved by addition of ethylene glyco l and stable liquid material was employed for calibration purposes. N- acetyl-beta-D-glucosaminidase isoenzymes were separated by a routine c hromatofocusing procedure on PBE 94. The addition of both metals to ly mphocytes inhibits lysosomal enzyme release. These data were supported by the plasma levels for the exposed subjects, in which enzyme levels were significantly decreased after either type of exposure. In the ge neral population of subjects not professionally exposed, the effect of lead appears to be masked by concomitant effects of alcohol consumpti on. Undoubtedly, some heavy metals can alter distribution of glycohydr olases of lysosomal origin between the intra-and extracellular environ ment, probably interfering with membrane mechanisms. Lysosomal enzymes seem to behave as sensitive biomarkers for early subclinical changes that might later lead to clinical disease. (C) 1997 Elsevier Science B .V.