Quantitation of DNA Adducts of Aristolochic Acids in Repair-Deficient Cells: A Mechanistic Study of the DNA Repair Mechanism.

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.

Remediation of aristolochic acid-contaminated soil by an effective advanced oxidation process.

Aristolochic acids (AAs) are persistent soil pollutants in the agricultural fields of the Balkan Peninsula that are endemic for Aristolochia clematitis L. This class of carcinogenic and nephrotoxic phytotoxins is taken up by crops through root absorption and contaminates staple foods across the peninsula. Human exposure to AAs via dietary intake has recently been recognized as a cause of Balkan endemic nephropathy. For the sake of public health, human exposure to AAs from all sources should be minimized in a timely manner. However, currently, there is no available remediation method to remove AAs from soil. In this study, we developed the first soil remediation method for AAs using Fenton's reagent (FR), a combination of ferrous ion and hydrogen peroxide, and optimized factors, including pH, temperature, time, and dose of FR, to achieve the best degradation performance. The maximum AA degradation efficiency was found to be >97% in soil with 500 µg kg-1 of AAs. We anticipate that this developed method, mediated via Fenton reaction, will be useful to effectively eliminate AAs from the Balkan farmlands.

Occurrence and Environmental Stability of Aristolochic Acids in Groundwater Collected from Serbia: Links to Human Exposure and Balkan Endemic Nephropathy.

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.