Lipid peroxidation as pathway of aluminium cytotoxicity in human skin fibroblast cultures: prevention by superoxide dismutase+catalase and vitamins E and C.
Lipid peroxidation is one of the main manifestations of oxidative damage and has been found to play an important role in the toxicity and carcinogenicity of many xenobiotics. In the present study, we investigated the possible induction of lipid peroxidation by aluminium in human foreskin fibroblast cultures by assaying the malondialdehyde (MDA) produced inside the cells. The MDA-thiobarbituric acid (TBA) adduct was assayed by HPLC using fluorometric quantification after extraction in n-butanol. Lactate dehydrogenase (LDH) release was used as a marker of aluminium toxicity. MDA production was significantly increased after 24 h incubation with aluminium and paralleled LDH release. Superoxide dismutase (SOD)+catalase and vitamins C and E added in the culture medium as oxygen radical and free radical scavengers were efficient in preventing MDA production by aluminium, indicating that oxidative processes are one of the main pathways whereby this metal induces cytotoxicity. The latter is also largely prevented, thus confirming the link between oxidative stress induced by aluminium and its cytotoxicity in human skin fibroblasts.
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Laboratory of Toxicology and Applied Hygiene, Faculty of Pharmaceutical Sciences, University of Victor Segalen, Bordeaux, France.
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D000535:Aluminum / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001205:Ascorbic Acid / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D008315:Malondialdehyde / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D016166:Free Radical Scavengers; D014810:Vitamin E; D008315:Malondialdehyde; D000535:Aluminum; D002374:Catalase; D013482:Superoxide Dismutase; D001205:Ascorbic Acid