Aristolochic acids (AAs), are natural constituents identified in Aristolochia plants utilized in Chinese traditional medicine and they are also parts of a lot of herbal remedies adopted all over the world. In human beings, AA exposure can lead to kidney toxicity or rare upper urinary tract cancer (UUC). Evidence has emerged, showing that AAs are associated with the development of Balkan endemic nephropathy (BEN) which is a progressive renal illness inflicting a large number of peasants dwelling in the Balkan Peninsula. Regrettably, how AAs get into the human food cycle and lead to kidney dysfunction is still elusive.

The hypothesis guiding the study was the possibility that free AAs derived from decayed Aristolochia clematitis in the fields would be uptaken from the soil by pla...[ Read more ]

Aristolochic acids (AAs), are natural constituents identified in Aristolochia plants utilized in Chinese traditional medicine and they are also parts of a lot of herbal remedies adopted all over the world. In human beings, AA exposure can lead to kidney toxicity or rare upper urinary tract cancer (UUC). Evidence has emerged, showing that AAs are associated with the development of Balkan endemic nephropathy (BEN) which is a progressive renal illness inflicting a large number of peasants dwelling in the Balkan Peninsula. Regrettably, how AAs get into the human food cycle and lead to kidney dysfunction is still elusive.

The hypothesis guiding the study was the possibility that free AAs derived from decayed Aristolochia clematitis in the fields would be uptaken from the soil by plants growing nearby, thereby transferring this potent human carcinogen and nephrotoxin into the edible parts. Applying the formerly created method of analysis which is sensitive and selective (Chan et al., 2007), the study measures AAs in lettuce, tomato, as well as spring onion planted in AA polluted land and culture medium. Results suggest that AAs are absorbed from the land and gathered biologically in lettuce in a way that depends on time as well as dose.

To better confirm the assumption that environmental contamination by AAs and root uptake of AAs in the contaminated soil could be one of the pathways by which AAs enter the human food chain, we also analyzed farmland soil and food crops collected from both non-endemic and endemic areas in Serbia, we discovered that environmental and food pollution by AAs from the decomposition of Aristolochia clematitis is one of the main causes to BEN. Data also showed AAs are highly stable in the soil environment and during the heat-treatment process, indicating AAs are persistent environmental and food contaminants and is able predisposed to be up taken by food crops and end upturned out in bread. As far as we know, this is the first research that agricultural soil and grains in the endemic area are being extensively contaminated with AAs. We believe the results from this report have disclosed a hidden, but important public health problem: the occurrence of a new type of potent nephrotoxic and carcinogenic toxicant in both the environment and food.

In other hand, although decades of research have gone, the potential impact on proteins is elusive, and the specific mechanism of nephrotoxicity remains unclear because of the observed toxicity of AA is poorly understood. In order to better understand the toxicological AA characteristics, the covalent and noncovalent interaction between AA and proteins was investigated in this study. Through mass spectrometry (MS) and fluorescence spectra, we characterized the protein binding characters of AA and BSA and lysozyme. In addition, a sensitive high-performance liquid chromatography together with fluorescence detection (HPLC-FLD) method was used to assess acid-labile albumin−AA ad-ducts in vitro managed a dietary-associated amount of aristolactams. We can also detected released aristolactams from AA-protein adducts in AA dosed SD-rats tissues. This is the first direct report to demonstrate both covalent and noncovalent binding of protein-AA complexes to the best of our knowledge.