The esters of p-hydroxy-benzoate (parabens) inhibit the release of lysosomal enzymes by mitogen-stimulated peripheral human lymphocytes in culture.
An in vitro test was set up to assess the release of lysosomal enzymes from cells and the effect on this process of the commonly used preservatives, parabens. Human peripheral lymphocytes, cultivated in vitro for 24 h in the presence or absence of phytohaemagglutinin (PHA; 5 mg/l), were used. After 1 day of incubation, PHA treatment caused an increased release (from 220 to 500%) of the lysosomal enzymes N-acetyl-beta-D-glucosaminidase, beta-D-glucuronidase, alpha-L-fucosidase and alpha-D-galactosidase. This enhancement was analytically reliable, and detectable with 1-5 micrograms of cell protein. Leakage of lactate dehydrogenase (LDH) underwent only a 20% increase on PHA treatment, indicating that the increased release of lysosomal enzymes was presumably due to secretion, not to cell damage. In PHA-stimulated lymphocytes, methyl-, ethyl-, propyl- and butyl-parabens caused a concentration-dependent diminution of the secretion of lysosomal enzymes. Butyl-paraben appeared to be the most potent inhibitor, causing a 45-50% inhibition at 0.06 mmol/l. With the other parabens, the inhibitory effect became statistically significant at about 0.25 mmol/l for alpha-L-fucosidase and alpha-D-galactosidase, and at 0.5 mmol/l for N-acetyl-beta-D-glucosaminidase and beta-D-glucuronidase. At 1 mmol/l inhibition was greater than 50% for all the enzymes and was more marked with the propyl derivative. Parabens did not influence the release of LDH, suggesting that they affected particularly the secretion of lysosomal enzymes. This supports the hypothesis that parabens are capable of affecting cellular function at concentrations which are likely to be reached in blood or tissues under conditions of common use.
Bairati
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C
Department of Medical Chemistry and Biochemistry, Medical School University of Milan, Italy.
Goi
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G
Lombardo
A
A
Tettamanti
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G
D000118:Acetylglucosaminidase / Q000097:blood; D000328:Adult; D002478:Cells, Cultured; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology*; D008934:Mitogens / Q000494:pharmacology*; D010226:Parabens / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D000519:alpha-Galactosidase / Q000097:blood; D005644:alpha-L-Fucosidase / Q000097:blood
D008934:Mitogens; D010226:Parabens; D010835:Phytohemagglutinins; D007770:L-Lactate Dehydrogenase; D000519:alpha-Galactosidase; D005966:Glucuronidase; D005644:alpha-L-Fucosidase; D000118:Acetylglucosaminidase