Aristolochic acid (AAs) is well known for its carcinogenicity and nephrotoxicity showed in weight loss treatment events in Belgium, as well as other safety problems in Taiwan and the Danube region. Nowadays, it becomes a serious worldwide problem due to multiple exposure ways and severe health hazard. The main ways of human exposed directly or indirectly to AAs include the misuse of AA-containing plants, the contact to contaminated soil, the uptake of contaminated food and the occupational exposure. In order to prevent the uptake of AAs, we should understand the process of AAs' transportation in the environment and focus on controlling the fate and transportation of AAs. These processes are essential for the risk assessment, prevention, and remediation of Aristolochia plants o...[ Read more ]

Aristolochic acid (AAs) is well known for its carcinogenicity and nephrotoxicity showed in weight loss treatment events in Belgium, as well as other safety problems in Taiwan and the Danube region. Nowadays, it becomes a serious worldwide problem due to multiple exposure ways and severe health hazard. The main ways of human exposed directly or indirectly to AAs include the misuse of AA-containing plants, the contact to contaminated soil, the uptake of contaminated food and the occupational exposure. In order to prevent the uptake of AAs, we should understand the process of AAs' transportation in the environment and focus on controlling the fate and transportation of AAs. These processes are essential for the risk assessment, prevention, and remediation of Aristolochia plants or crops contaminated with AAs. In this study, the uptake efficiency of AAs by plants under different pH was investigated. The results showed that the RCF of AAs absorption index decreased with the increase of pH, which indicated that plants contain higher concentration of AAs in the acidic environment. The RCF coefficient of aristolochic acid I (AAI) in plants is higher than that of aristolochic acid II (AAII), which indicated that AAI is easier to be accumulated in plants. Accordingly, food contamination by AAs was due to the pollution in soil or water and the plant absorption of AAs.

AAs enter into human body through food-borne pathway and will induce several diseases including the renal diseases and urothelial diseases. The mechanism is hypothesized both in bimolecular level and cellular levels but the further studies are required for revealing the entire mechanism of AAs pathogenicity. Biomarkers are important indicators to identify the occurrence of diseases in the biological system, and their evaluation is very useful for clinical prevention. Firstly, the serum creatinine of rats fed AAI was measured. We found that the creatinine in serum of healthy rats was higher than that of healthy rats in 28 days and 60 days. This indicated that 30 mg/kg of AAI could cause renal damage in a month. AAI is one of the examples of nephrotoxic substances. Studies have shown that AAs are associated with renal fibrosis. The evidence suggests that DNA covalently binds to AAs and forms stable and persistent adducts with organ specificity. Previous studies did not cover all major organs of rats, and the sensitivity of detection methods was quite low. Thus, this part of study included the quantification of AAI-DNA in all major organs of rats and the calculation of half-life of adducts. The results showed that the adducts level in the forestomach were the highest at day 1, while those in the kidney and liver were lower. In addition, 7-(Deoxyadenosin-N⁶-yl)-aristolactam I (dA-AAI) is the predominant adduct in each organ at all time points. Based on the results in 60 days, we observed that the level of adducts in dA-AAI was organ specific. The results showed that the dA-AAI retain the longest time in kidney tissue which was defined as the target organ. The results support the conclusion that adducts are more durable in target organs than in non-target organs.

DNA repair is a necessary defense system against in organisms this genotoxic damage. AA-DNA damage repair mechanism has been systematically and thoroughly studied in eukaryotes, but the damage caused by AAs in prokaryotes is not yet clear. We used the wild type, NER and BER deficient strains of Escherichia coli (E.coli) as experimental subjects. The level of DNA adducts induced by AA1 and AAH was detected for the evaluation the DNA damage of AAs to E.coli. The results showed that AAs cause DNA damage in E.coli, and the level of dA-AAI and dG-AAI was positively correlated with the dose. Nucleotide excision repair· (NER) was found to be the main repair mechanism by comparing different strains and the UvrABC are the main proteins of AAs-DNA damage repair.

Overall, it is suggested that the food monitoring and fate studies of AAs could contribute to the dietary exposure risk assessment via direct or modeling estimation. Furthermore, the development of biomarkers for AAs and their derivatizes is expected to help assessing the toxicity of them and thus established the strict regulations on AAs.