Seeds from birthwort (Aristolochia clematis), a plant which grows in wheat fields in the Balkan region and which has been used throughout Europe and Asia as an herbal remedy for 2000 years, is contaminating the wheat grain, leading to a devastating kidney disease affecting rural residents in that region, a study led by Dr. Arthur Grollman of Stony Brook University suggests.
Endemic (Balkan) nephropathy (EN), a kidney disease found in farming villages in Bosnia, Bulgaria, Croatia, Romania and Serbia, progresses rapidly to chronic renal failure and is strongly associated with upper urinary tract cancer.
To investigate the environmental source of this disease, Dr. Arthur Grollman, Distinguished Professor of Pharmacological Sciences at Stony Brook University Medical Center, and his colleagues in the US, in collaboration with researchers in Croatia, analyzed DNA samples obtained from renal tissues of patients affected by the disease. The researchers detected DNA damage caused by a chemical called aristolochic acid in patients with EN but not in patients with other forms of chronic kidney disease. They also discovered the mutational fingerprint of aristolochic acid in a gene associated with EN-related urinary tract cancer.
Because this toxin is produced by the Aristolochia clematitis, or birthwort, plant, which is native to the region, Dr. Grollman and his colleagues postulate that contamination of grain with seeds of this plant, leading to chronic dietary poisoning, is the cause of endemic nephropathy.
This finding has significant implications for strategies to eliminate EN from the Balkan peninsula and for dealing with kidney disease in other areas where the plant is used in traditional herbal remedies. Additionally, by bringing to bear genomics, pathology, environmental sciences, biochemistry, and clinical medicine, Dr. Grollman has created an important approach for research in other environmental diseases.
Journal Article: Aristolochic acid and the etiology of endemic (Balkan) nephropathy, by Arthur P. Grollman, Shinya Shibutani, Masaaki Moriya, Fredrick Miller, Lin Wu, Ute Moll, Naomi Suzuki, Andrea Fernandes, Thomas Rosenquist, Zvonimir Medverec, Krunoslav Jakovina, Branko Brdar, Neda Slade, Robert J. Turesky, Angela K. Goodenough, Robert Rieger, Mato Vukelic, and Bojan Jelakovic, and published in Proceedings of the National Academy of Sciences (July 17).
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