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 foo d and is nephrotoxic for all animal species studied so far. OTA is imm unosuppressive, genotoxic, teratogenic and carcinogenic, It is a struc tural analogue of phenylalanine and contains a chlorinated dihydroisoc oumarinic moiety. Ochratoxin A inhibits protein synthesis by competiti on with phenylalanine in the phenylalanine-tRNA aminoacylation reactio n. Recently lipid peroxidation induced by OTA has been reported, indic ating that the lesions induced by this toxin could also be related to oxidative damage. An attempt to prevent its toxic effect, mainly the l ipid peroxidation, has been made using aspartame (L-aspartyl-L-phenyla lanine methyl ester) a structural analogue of both OTA and phenylalani ne, piroxicam, a non steroidal anti-inflammatory drug and superoxide d ismutase + catalase (endogenous oxygen radical scavengers). Lipid pero xidation was assayed in monkey kidney cells (Vero cells) treated by in creasing concentrations of OTA (5-50 mu M). After 24 h incubation OTA induced lipid peroxidation in Vero cells in a concentration dependent manner, as measured by malonaldehyde (MDA) production. The MDA product ion, 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 super oxide dismutase (SOD) + catalase (25 mu g/ml each) the MDA production induced by OTA was significantly decreased. At 50 mu M of OTA concentr ation (optimal production of MDA) the MDA production decreased from 10 41.5 +/- 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 th an OTA) and aspartame (at equimolar concentration). These molecules al so partially prevented the OTA-induced leakage of MDA in the culture m edium. (C) 1997 Elsevier Science Ireland Ltd.