Urothelial Carcinoma Associated with the Use of a Chinese Herb (Aristolochia fangchi)

Is aristolochic acid a risk factor for Balkan endemic nephropathy‐associated urothelial cancer?

“…1 Moreover, the dA-AAI adduct showed an apparently life-long persistence in various organs in rats and it was still detectable in renal tissue of Belgian AAN patients more than 7 years after the patients stopped taking the herbal slimming regimen. 4,6 Because the renal tissue samples were collected between 1987-90 (Table I) our results confirm that the dA-AAI adduct is a suitable biomarker for exposure to AA years later.…”

“…4,7 A major role of OTA in AAN was excluded. In this pilot study we want to assess AA exposure in endemic areas for BEN.…”

“…11 AAN patients have been exposed to high amounts of AA within a few months (Ϸ15-20 months) providing a reason for the rapid development of AAN and AAN-associated urothelial tumors (Ϸ2-6 years). 2,4,11,12 In contrast, people in endemic areas for BEN might have been exposed chronically to low amounts of AA over years, which might explain the slow development of BEN and BEN-associated urothelial malignancy.…”

Human hepatic and renal microsomes, cytochromes P450 1A1/2, NADPH:Cytochrome P450 reductase and prostaglandin H synthase mediate the formation of aristolochic acid‐DNA adducts found in patients with urothelial cancer

“…2) as those obtained in vivo in rats and humans reported previously. 10,11,[17][18][19][20][21][22][23] These adduct spots formed by AAI showed the same migration on PEI-cellulose TLC plates and on reversed-phase HPLC as those of synthetic standards 19 (Fig. 3).…”

“…Therefore, it has been proposed to designate the interstitial nephropathy in which the unequivocal role of AA has been fully documented as aristolochic acid nephropathy. 7,8 Recently, a high prevalence of urothelial cancer was found in a large cohort of patients suffering from aristolochic acid nephropathy in Belgium 9,10 and a case with urothelial cancer has also been described in the United Kingdom. 11 It is also noteworthy that AA consumption may be a cause for the development of a similar type of fibrosis of the kidneys with malignant transformation of the urothelium, the Balkan endemic nephropathy, [12][13][14][15] which is widely found in certain areas of Rumania, Croatia, Bosnia, Serbia and Bulgaria along the Danube river basin.…”