6 May 2019

Aristolochic acids - the culprit behind Balkan endemic nephropathy

Natural toxin

Aristolochic acids are a mixture of nitrophenanthrene carboxylic acids. They are produced by Aristolochia, a genus comprising over 500 species widespread all over the world. The compounds are nephrotoxic and carcinogenic, and are the causative factor for the Balkan endemic nephropathy.

Click figure for interactive 3D image

Aristolochic acids (AAs) are a family of phytochemicals found in all Aristolochia sp. that spread worldwide. They are structurally nitrophenanthrene carboxylic acids, principally composed of two metabolites, aristolochic acid I (AAl, CAS 313-67-7) and aristolochic acid II (AAll, CAS 475-80-9).

AAs are both nephrotoxic and carcinogenic. Chronic exposure to AA-containing plants, i.e. Aristolochia clematitis (birthwort) has been convinced to be the reason for Balkan endemic nephropathy (BEN), a familial progressive disease occurred in rural villages along Danube river. Involved countries include Serbia, Bulgaria, Romania, Bosnia and Herzegovina and Croatia. Moreover, AAs are also associated with Chinese herbs nephropathy (CHN), a disease outbreaking in Belgium in 1993 when women inadvertently ingested Aristolochia fangchi as a weight-loss supplement.

In a very recent published study of the agricultural fields in Serbia, AAs are proved to be persistent soil contaminants to where high BEN incidence has been observed. The compounds remain stable in soil for more than 9 months, with an initial drop of 40-50% in concentration during the first 3 months. Considering their high mobility, persistency and toxicity, it could be an interesting case-study for the network to investigate the possible impact of these natural toxins on the aquatic ecosystem.

Aristolochic acid I: COc1cccc2c1cc(c3c2c4c(cc3C(=O)O)OCO4)[N+](=O)[O-]
Aristolochic acid II: c1ccc2c(c1)cc(c3c2c4c(cc3C(=O)O)OCO4)[N+](=O)[O-]


  • Grollman AP, Scarborough J, Jelaković B. Aristolochic acid nephropathy: an environmental and iatrogenic disease. Advances in molecular toxicology. 2009 Jan 1;3:211-27.
  • Li W, Chan CK, Liu Y, Yao J, Mitić B, Kostić EN, Milosavljević B, Davinić I, Orem WH, Tatu CA, Dedon PC. Aristolochic acids as persistent soil pollutants: Determination of risk for human exposure and nephropathy from plant uptake. Journal of agricultural and food chemistry. 2018 Oct 5;66(43):11468-76.