Aristolochic
acids (AAs) have been known as potent nephrotoxins
since the use of AA-containing herbal medicines was linked with a
series of sporadic renal fibrotic nephropathy cases, and yet an estimated
100 million people worldwide are still at risk today because of continued
use of similar medicines. However, a similar nephropathic condition
is endemic in the rural Balkan regions (e.g., Serbian farming villages)
and AAs were again found to be the causative agents. In the case of
this Balkan endemic nephropathy, AAs were found to have originated
from a widespread local weed Aristolochia clematitis L. In this study, we tested the hypothesis that AAs released from
decomposition of A. clematitis were
also being leached into groundwater, thus polluting the drinking water
of local residents. We initiated the study by developing a dispersive
solid-phase extraction-based sample preparation method for water samples
suspected of AA contamination. The validated method was then coupled
with a liquid chromatography-tandem mass spectrometric method to measure
AAs in groundwater samples collected from Serbia. Our study revealed
for the first time that groundwater in Serbia is extensively contaminated
with AA-I, at ng/L levels. Results also showed that AAs are long-lived
water contaminants, with no observable concentration changes over
a 2-month period of sample storage.
Accumulating evidence has revealed that nephrotoxic and carcinogenic aristolochic acids (AAs) released from decaying Aristolochia clematitis L. weeds are soil and food grain contaminants in the Balkan Peninsula, while AA toxicity has been linked to induced DNA damage. In this study, we investigated the DNA repair mechanism that excises the aristolactam-DNA adducts in gene-knockout Escherichia coli cells. These results demonstrated that cell lines deficient in nucleotide excision repair (NER) machinery accumulated higher adduct levels, indicating that NER is the major mechanism responsible for the repair of these lesions. Furthermore, data also revealed the involvement of base excision repair enzymes in repairing the lesions but with lower contribution than NER.
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