Abstract:Aflatoxin B 1 (AFB 1 ) and ochratoxin A (OTA) are contaminants which co-occurred in the same food such as cereals. The few studies performed on their interactive effect had revealed additive or antagonistic cytotoxic effect according to cells endpoints and concentrations of both mycotoxins. The aim of the present study was to investigate in a possible influence of very low level of ochratoxin A in aflatoxin B 1 toxic action regarding cellular endpoints such as malonedialdehyde (MDA) production and cells viability as evaluated by lysosome and mitochondria integrities and cell lactate dehydrogenase (LDH) leakage. OTA (20nM) and AFB 1 were tested in combination in both human intestinal (Caco-2) and hepatoma (HepG2) cells lines. As results, OTA alone tested at 20nM was not cytotoxic and did not induce MDA production in both Caco-2 and HepG2 cells line. Interestingly, combined to AFB 1 (10µM), OTA enhanced markedly AFB 1 cytotoxic effect. OTA significantly increased cell lysosomes damage induced by AFB 1 from 24% to 38% (+14%) and from 28% to 43% (+15%) respectively in Caco-2 and HepG2 cells line (p<0.05). Similarly, OTA enhanced inhibition of mitochondria succinate dehydrogenase activity induced by AFB 1 until to +15% and +6% respectively in Caco-2 and HepG2 cells line (p<0.05). On cell necrosis marker, the mixture of OTA and AFB 1 induced more LDH leakage when compared to AFB 1 alone with increase of +14% and +12% respectively in Caco-2 and HepG2 cells line (p<0.05). Finally, on MDA production, AFB 1 + OTA induced more intensively MDA production when compared to AFB 1 alone with +49% and +110% of increasing in both Caco-2 and HepG2 cells line (p<0.01). Taken together, our results suggested that combined AFB 1 and OTA induced all the toxicities observed with the mycotoxins separately but more intensively suggesting synergistic or potentiating effect. Moreover, AFB 1 or its association with OTA had been found very potent in human hepatic cells HepG2 in necrosis induction but especially in lipids oxidative damage confirming oxidative stress as one of keys pathways in toxic action of AFB 1 .