Early Cardiovascular Dysfunction in Prehypertension

Synergistic Interaction of Polycyclic Aromatic Hydrocarbons, Phthalate Esters, or Phenol on DNA Adduct Formation by Aristolochic Acid I: Insights into the Etiology of Balkan Endemic Nephropathy

“…14,40 AA−DNA adduct formation caused by exposure to AAs has been well studied for its potential causative role in the development of renal fibrosis and carcinomas of the upper urinary tract of patients suffering from BEN. 12,28 Although BEN is known to be an environmentally induced disease and the interactions between multiple environmental pollutants having profound effects on toxicity have been well documented, 5,8 it is only recently that we have begun to appreciate that the interactions of AAs with other environmental pollutants, such as ochratoxin A, 25 PAHs, and phthalate esters, 26 could be an important factor in the etiology of BEN.…”

“…12−14 It was found that AAs were present in significant concentrations in the soil of crop cultivation fields that contained a common weed Aristolochia clematitis found in the Balkan region. 12,14 This AA-producing weed can be found extensively in cultivated fields, and upon decay, its AA contents are retained in the soil. 14,15 The free AAs are taken up by food crops through root absorption and subsequently deposited into grains that farmers harvest to produce bread and other staples.…”

“…14,15 The free AAs are taken up by food crops through root absorption and subsequently deposited into grains that farmers harvest to produce bread and other staples. 12 AA−DNA adducts were identified in DNA samples isolated from the kidneys of patients suffering from BEN. 16,17 These results, together with experiments demonstrating that AAs induce similar carcinogenic and nephrotoxic effects on laboratory rodents, 18−21 have provided compelling evidence to assert the causative role of AA exposure in the etiology of BEN.…”

“…While the bulk of previous studies on BEN etiology has focused on the toxicological mechanisms of individual toxicants, e.g., AAs, 12,22 there is an emerging appreciation for the interaction between coexposed toxicants in disease pathology. For example, coexposure to aristolochic acid II (AAII), 23,24 ochratoxin A, 25 and some PAHs 26 Figure 1), which is the most abundant and most mutagenic species of the AA family.…”