It has been reported that OTA is hepatotoxic, nephrotoxic,
immunotoxic and teratogenic in animals and may cause kidney and
liver tumours in rats and mice. OTA is considered by some to be
involved in the Balkan Endemic Nephropathy (BEN), a severe kidney
pathology, widespread in SoutheEastern Europe and associated
with urinary tracts tumours . However
in recent years some authors have reported that BEN is due to
exposure to aristolochic acid . Acute lethal
doses of OTA cause severe haemorrhages, coagulation and widespread
necroses. In all animal species tested, OTA causes severe
renal toxicity and it may exert a genotoxic role by generating
reactive oxygen species (ROS) . OTA can accumulate
at high rates in proximal tubule cells, where organic anion
transporters (OAT) 1 and 3 it take up it from the interstitium . Possible mechanisms of OTA adverse effects on health
can include genotoxicity (Pfohl-Leszkowicz and Manderville, 2012),
histone acetyltransferase (HAT) inhibition and
cytoskeleton destabilization. Studied showed
that OTA inhibits the nuclear factor erythroid 2-like (Nrf2), which
represents the major oxidative stress response and regulates the
transcription of genes implied into reduction of ROS and quinones
and glutathione synthesis