Prevention of lipid peroxidation induced by ochratoxin A in Vero cells in culture by several agents.
Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus ochraceus as well as other moulds. This mycotoxin contaminates animal feed and food and is nephrotoxic for all animal species studied so far. OTA is immunosuppressive, genotoxic, teratogenic and carcinogenic. It is a structural analogue of phenylalanine and contains a chlorinated dihydroisocoumarinic moiety. Ochratoxin A inhibits protein synthesis by competition with phenylalanine in the phenylalanine-tRNA aminoacylation reaction. Recently lipid peroxidation induced by OTA has been reported, indicating that the lesions induced by this toxin could also be related to oxidative damage. An attempt to prevent its toxic effect, mainly the lipid peroxidation, has been made using aspartame (L-aspartyl-L-phenylalanine methyl ester) a structural analogue of both OTA and phenylalanine, piroxicam, a non steroidal anti-inflammatory drug and superoxide dismutase+catalase (endogenous oxygen radical scavengers). Lipid peroxidation was assayed in monkey kidney cells (Vero cells) treated by increasing concentrations of OTA (5-50 microM). After 24 h incubation OTA induced lipid peroxidation in Vero cells in a concentration dependent manner, as measured by malonaldehyde (MDA) production. The MDA production, in Vero cells, was significantly increased by 50.5% from 694.1 +/- 21.0 to 1041.5 +/- 23.5 pmol/mg of protein. In the presence of superoxide dismutase (SOD)+catalase (25 micrograms/ml each) the MDA production induced by OTA was significantly decreased. At 50 microM of OTA concentration (optimal production of MDA) the MDA production decreased from 1041.5 +/- 23.5 to 827.5 +/- 21.3 pmol/mg of protein. SOD and catalase, when applied prior to the toxin, seemed to prevent lipid peroxidation more efficiently than piroxicam (at a ten-fold higher concentration than OTA) and aspartame (at equimolar concentration). These molecules also partially prevented the OTA-induced leakage of MDA in the culture medium.
Baudrimont
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Laboratoire de Toxicologie et d'Hygiène appliquée, UFR des Sciences Pharmaceutiques, Université Victor Segalen Bordeaux 2, France.
Ahouandjivo
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Creppy
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001218:Aspartame / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D016166:Free Radical Scavengers / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D015394:Molecular Structure; D009183:Mycotoxins / Q000633:toxicity; D009793:Ochratoxins / Q000633:toxicity*; D010894:Piroxicam / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D013858:Thiobarbiturates / Q000378:metabolism; D014709:Vero Cells
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D009183:Mycotoxins; D009793:Ochratoxins; D017382:Reactive Oxygen Species; D013858:Thiobarbiturates; D010894:Piroxicam; C025589:ochratoxin A; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; C029684:thiobarbituric acid; D001218:Aspartame