Antioxidative vitamins decrease cytotoxicity of HEMA and TEGDMA in cultured cell lines.
OBJECTIVE
In a previous study it was postulated that toxicity of 2-hydroxyethylmethacrylate (HEMA) and triethleneglycoldimethacrylate (TEGDMA) is based on oxidative metabolites. In this study the influence of antioxidative vitamins (including uric acid) on the toxicity of HEMA or TEGDMA was tested. Toxicity of HEMA and TEGDMA was determined in rat alveolar epithelial L2, human malignant A549, and human fibroblast-like 11Lu cells by inhibition of methionine incorporation (as a marker of protein synthesis inhibition) and by determination of glutathione depletion, as well as by measurement of GSSG increase.


RESULTS
Toxicity of the composite components HEMA and TEGDMA was demonstrated by GSH depletion as the most sensitive method. Five hundred micromoles per litre Vitamin C or 250 micromol/l Vitamin E were mostly able to decrease toxicity of HEMA and TEGDMA in the cell lines tested. In addition, 250 micromol/l Vitamin A was only effective in L2 cells impairing HEMA toxicity and 250 micromol/l uric acid impairing TEGDMA toxicity as assessed by decreased GSH depletion. In A549 cells only methionine incorporation inhibition but not GSH depletion was significantly affected. By contrast, in 11Lu cells methionine incorporation inhibition was not significantly changed, but GSH depletion was.


CONCLUSIONS
The postulated mechanism of HEMA or TEGDMA toxicity based on radical metabolites is supported by the effectivity of the antioxidative substances tested in mitigating toxicity and by the greater susceptibility of the glutathione redox system as compared to protein synthesis inhibition in assessing toxicity.
Walther
U I
UI
Walther-Straub-Institut für Pharmakologie und Toxikologie der Ludwig-Maximilians-Universität, Nussbaumstr. 26, 80336 München, Germany. udo.walther@lrz.uni-muenchen.de
Siagian
I I
II
Walther
S C
SC
Reichl
F X
FX
Hickel
R
R
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001672:Biocompatible Materials / Q000633:toxicity; D002460:Cell Line; D003188:Composite Resins / Q000633:toxicity*; D005978:Glutathione / Q000032:analysis; D019803:Glutathione Disulfide / Q000032:analysis; D005980:Glutathione Reductase; D006801:Humans; D008689:Methacrylates / Q000633:toxicity*; D008715:Methionine / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D011092:Polyethylene Glycols / Q000633:toxicity*; D011109:Polymethacrylic Acids / Q000633:toxicity*; D051381:Rats; D013880:Thioredoxin-Disulfide Reductase; D014527:Uric Acid / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology*
D000975:Antioxidants; D001672:Biocompatible Materials; D003188:Composite Resins; D008689:Methacrylates; D011109:Polymethacrylic Acids; D014815:Vitamins; D014810:Vitamin E; C020946:triethylene glycol dimethacrylate; D014527:Uric Acid; D011092:Polyethylene Glycols; C005044:hydroxyethyl methacrylate; D008715:Methionine; D009247:NADH, NADPH Oxidoreductases; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase; C424443:Txnrd3 protein, mouse; D005978:Glutathione; D001205:Ascorbic Acid; D019803:Glutathione Disulfide