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Effects of flavonoids in ochratoxin A-induced toxicity

Ochratoxin A (OTA) is a widespread mycotoxin produced by several species of fungi Aspergillus and Penicillium. OTA was found in relative high concentrations in human sera in areas where Endemic Nephropathy (EN) occurs. Since the occurrence of high serum OTA is not restricted to EN areas the link between OTA exposure and EN remains yet to be verified. However, animal experiments show that OTA is a potent nephrotoxic and carcinogenic agent. In addition, it adversely affects blood coagulation and the immune response. OTA-induced oxidative stress may explain its genotoxic effects and apoptosis, which in turn are likely to play important roles in the development of chronic tubulointerstitial nephritis. The aim of this study was to investigate the cell defence impact of flavonoids in OTA treated cell lines. MDCK, LLC-PK1, HeLa and K562 cell lines were exposed to 1 micro M of quercetin, kaempferol, myricetin naringenin and apigenin and /or the different doses of OTA (0.1 to 10 micro M OTA/ mL of medium) for 24 hrs. We studied the effects of OTA and flavonoids on cell viability and the type of cell death (apoptosis or necrosis), total antioxidative status, reduced-oxidized GSH-GSSG levels and intracellular ATP concentration. The free radical scavenging ability of flavonoids with different substitution patterns were also tested. We used DPPH• radical scavenging assay. The decreased total antioxidant status during exposure to OTA would emphasise the role of cellular antioxidants in the cell defence mechanisms against oxidative stress. All investigated flavonoids possessed scavenging activity against DPPH radicals, but they exhibited effects of different magnitude. The maximal antiradical activity was recorded for myricetin and quercetin, respectively. We conclude that the administration of antioxidative adjuvants such as flavonoids could be used as a preventive action or as a therapeutic intervention in OTA-induced toxicity.

ochratoxin A; apoptosis; necrosis; quercetin; kaempferol; myricetin naringenin; apigenin

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