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Balkan endemic nephropathy is a chronic tubulointerstitial disease with insidious onset, slowly progressing to end-stage renal disease and frequently associated with urothelial carcinoma of the upper urinary tract (UTUC). It was described in South-East Europe at the Balkan peninsula in rural areas around tributaries of the Danube River. After decades of intensive investigation, the causative factor was identified as the environmental phytotoxin aristolochic acid (AA) contained in Aristolochia clematitis, a common plant growing in wheat fields that was ingested through home-baked bread. AA initially was involved in the outbreak of cases of rapidly progressive renal fibrosis reported in Belgium after intake of root extracts of Aristolochia fangchi imported from China. A high prevalence of UTUC was found in these patients. The common molecular link between Balkan and Belgian nephropathy cases was the detection of aristolactam-DNA adducts in renal tissue and UTUC. These adducts are not only biomarkers of prior exposure to AA, but they also trigger urothelial malignancy by inducing specific mutations (A:T to T:A transversion) in critical genes of carcinogenesis, including the tumor-suppressor TP53. Such mutational signatures are found in other cases worldwide, particularly in Taiwan, highlighting the general public health issue of AA exposure by traditional phytotherapies. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance: in the 1990s, a Belgian cohort of more than 100 patients reported cases of Aristolochic Acid Nephropathy (AAN). This progressive renal and interstitial fibrosis, frequently associated with urothelial malignancies, was consecutive to the Chinese-herbs based slimming capsules intake where a plant Stephania tetrandra S. Moore was replaced by a highly genotoxic Aristolochia species. 70% of the Belgian patients evolved into end-stage renal disease, requiring dialysis or renal transplantation. Furthermore the prevalence of upper urinary tract carcinoma was found alarmingly high in these patients. The Aristolochia adulteration was blamed for the intoxication cases and, to the best of our knowledge, the prescription itself has not been further investigated. Aim of the study This work proposes to evaluate the in vitro cytotoxicity and genotoxicity of Aristolochia and Magnolia traditional aqueous decoctions and their association. Materials and methods The cytotoxicity of extracts has been assessed by a MTT cell proliferation assay and the genotoxicity by measuring the presence of γ-H2AX, a phosphorylated histone associated with DNA damages. Results Treating cells for 24 h with a mixture 1:1 of Magnolia officinalis and Aristolochia baetica decoctions led to an increase in the production of γ-H2AX. Conclusions This genotoxic potentiation warrants further studies but may lead to an explanatory factor for the “Chinese herb nephropathy” cases. [ABSTRACT FROM AUTHOR]

A new renal disease called ‘Chinese-herb nephropathy’ (CHN) has been reported to occur in women who have ingested slimming pills containing powdered extracts of the Chinese herb Stephania tetrandra (ST). Moderate to end-stage renal disease developed, requiring renal replacement therapy by dialysis or transplantation. Phytochemical analyses of the pills revealed the presence of aristolochic acids (AA) instead of tetrandrine, suggesting the substitution of ST (Han fang ji) by Aristolochia fangchi containing nephrotoxic and carcinogenic AA. A typical histological feature of CHN is a progressive interstitial fibrosis leading to a severe atrophy of the proximal tubules, as documented by the urinary excretion rates of markers of tubular integrity (reduction of neutral endopeptidase enzymuria and high levels of microproteinurias). Removal of the native kidneys and ureters in end-stage CHN patients provided a high prevalence of urothelial carcinoma (46%). Tissue samples contained AA-related DNA adducts, which are not only specific markers of prior exposure to AA but are also directly involved in tumorigenesis. Exposure to Aristolochia species (spp.) is associated with the development of renal interstitial fibrosis (CHN) and urothelial cancer in humans. Health professionals should be aware that in traditional Chinese medicine, Aristolochia spp. are considered interchangeable with certain other herbal ingredients and are also sometimes mistaken for ST, Akebia, Asarum, Clematis spp. and Cocculus spp. in herbal remedies. [Copyright &y& Elsevier]

Background. Renal failure after ingestion of Chinese herbs between 1990 and 1992 was related to the replacement of Stephania tetrandra by Aristolochia fangchi (ST–AF), containing nephrotoxic and carcinogenic aristolochic acids. However, the relationship between ST–AF and renal failure is still a matter of debate. We therefore tested the impact of the ST–AF ingested dose on the progression of renal function deterioration. [ABSTRACT FROM PUBLISHER]