Evidence of exposure to aristolochic acid in patients with urothelial cancer from a Balkan endemic nephropathy region of Romania

2012 ◽  
Vol 53 (8) ◽  
pp. 636-641 ◽  
Author(s):  
Heinz H. Schmeiser ◽  
Jill E. Kucab ◽  
Volker M. Arlt ◽  
David H. Phillips ◽  
Monica Hollstein ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Aristolochic Acid ◽  
Balkan Endemic Nephropathy ◽  
Endemic Nephropathy

scholarly journals Is aristolochic acid a risk factor for Balkan endemic nephropathy-associated urothelial cancer?

2002 ◽  
Vol 101 (5) ◽  
pp. 500-502 ◽  
Author(s):  
Volker M. Arlt ◽  
Dusan Ferluga ◽  
Marie Stiborova ◽  
Annie Pfohl-Leszkowicz ◽  
Mato Vukelic ◽  
...  
Keyword(s):  
Risk Factor ◽  
Urothelial Cancer ◽  
Aristolochic Acid ◽  
Balkan Endemic Nephropathy ◽  
Endemic Nephropathy

scholarly journals Aristolochic acid mutagenesis: molecular clues to the aetiology of Balkan endemic nephropathy-associated urothelial cancer

2007 ◽  
Vol 28 (11) ◽  
pp. 2253-2261 ◽  
Author(s):  
V. M. Arlt ◽  
M. Stiborova ◽  
J. vom Brocke ◽  
M. L. Simoes ◽  
G. M. Lord ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Aristolochic Acid ◽  
Balkan Endemic Nephropathy ◽  
Endemic Nephropathy

scholarly journals Contribution of biotransformation enzymes to the development of renal injury and urothelial cancer caused by aristolochic acid: urgent questions, difficult answers

2008 ◽  
Vol 1 (1) ◽  
pp. 8-12 ◽  
Author(s):  
Marie Stiborová ◽  
Jiří Hudeček ◽  
Eva Frei ◽  
Heinz Schmeiser
Keyword(s):  
Renal Injury ◽  
Urothelial Cancer ◽  
Aristolochic Acid ◽  
Cytochromes P450 ◽  
Balkan Endemic Nephropathy ◽  
Kidney Fibrosis ◽  
Relative Contribution ◽  
Biotransformation Enzymes ◽  
Endemic Nephropathy

Contribution of biotransformation enzymes to the development of renal injury and urothelial cancer caused by aristolochic acid: urgent questions, difficult answersIngestion of aristolochic acid (AA) is associated with the development of aristolochic acid nephropathy, which is characterized by chronic renal failure, tubulointerstitial fibrosis and urothelial cancer. AA may also cause a similar type of kidney fibrosis with malignant transformation of the urothelium, the Balkan endemic nephropathy. Understanding which enzymes are involved in AA activation and/or detoxication is important in the assessment of a susceptibility to this carcinogen. The most important human enzymes activating AA by simple nitroreductionin vitroare hepatic and renal cytosolic NAD(P)H:quinone oxidoreductase, hepatic microsomal cytochrome P450 1A2 and renal microsomal NADPH:cytcohrome P450 reductase, besides cyclooxygenase, which is highly expressed in urothelial tissue. Despite extensive research, contribution of most of these enzymes to the development of these diseases is still unknown. Hepatic cytochromes P450 were found to detoxicate AA in mice, and thereby protect the kidney from injury. However, which of cytochromes P450 are the most important in this process both in animal models and in humans have not been entirely resolved as yet. In addition, the relative contribution of enzymes found to activate AA to species responsible for induction of urothelial cancer in humans remains still to be resolved.

Balkan endemic nephropathy and associated urothelial cancer

2008 ◽  
Vol 5 (2) ◽  
pp. 105-112 ◽  
Author(s):  
Vladisav Stefanovic ◽  
Zoran Radovanovic
Keyword(s):  
Urothelial Cancer ◽  
Balkan Endemic Nephropathy ◽  
Endemic Nephropathy

scholarly journals Molecular Markers in Upper Urothelial Carcinoma Associated to Balkan Endemic Nephropathy. Aristolochic Acid as the Major Risk Factor of the Worldwide Disease

2009 ◽  
Vol 9 ◽  
pp. 1360-1373 ◽  
Author(s):  
Ljubinka Jankovic Velickovic ◽  
Takanori Hattori ◽  
Vladisav Stefanovic
Keyword(s):  
Regression Analysis ◽  
Urothelial Carcinoma ◽  
Growth Stage ◽  
Aristolochic Acid ◽  
Balkan Endemic Nephropathy ◽  
Specific Cell ◽  
Ki 67 ◽  
High Stage ◽  
Endemic Nephropathy

The role of aristolochic acid in the etiology of Balkan endemic nephropathy (BEN) and associated upper urothelial carcinoma (UUC) was recently confirmed. The aim of this study was to determine the marker(s) specific for BEN-associated UUC. A total of 82 patients with UUC (38 from the BEN region and 44 control tumors) were included in the study. The Ki-67 index in BEN tumors correlated with the grade and multifocality (p< 0.05), but in regression analysis, only the grade of BEN tumor. The p53 index was significantly higher in BEN than in control tumors (p< 0.05), as well as the alteration of p53 (p< 0.05). BEN low-stage tumors, tumors without limphovascular invasion (LVI), and tumors of the renal pelvis had a higher p53 index than the control tumors (p< 0.05, 0.01, 0.05, respectively). The Ki-67 index was higher in control tumors with high-stage and solid growth than in BEN UUC (p < 0.050, 0.005). The Ki-67 correlated with the grade, growth, stage, LVI, and multifocality of UUC on the best way, but not with the group. In regression analysis, only multifocality of UUC had predictive influence on Ki-67 activity (p< 0.001). P53 correlated with the grade, growth, and group (p< 0.05). This investigation identifies the p53 pathway as the specific cell cycle marker involved in BEN-associated UUC.

scholarly journals Arterial Stiffness in Balkan Endemic Nephropathy, an Environmental Form of Aristolochic Acid Nephropathy

2018 ◽  
Vol 5 ◽  
Author(s):  
Vedran Premužić ◽  
Vanja Ivković ◽  
Ninoslav Leko ◽  
Želimir Stipančić ◽  
Sandra Karanović ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Aristolochic Acid ◽  
Balkan Endemic Nephropathy ◽  
Aristolochic Acid Nephropathy ◽  
Endemic Nephropathy

Aristolochic acid nephropathy caused by ingestion of herbal medicinal products

2015 ◽  
Author(s):  
M. Refik Gökmen ◽  
Graham M. Lord
Keyword(s):  
Aristolochic Acid ◽  
Herbal Medicines ◽  
Balkan Endemic Nephropathy ◽  
Herbal Products ◽  
Herbal Medicinal Products ◽  
Aristolochic Acid Nephropathy ◽  
Endemic Nephropathy ◽  
Risk Of Malignancy ◽  
Urothelial Malignancy ◽  
Mechanisms Of Carcinogenesis

Aristolochic acid nephropathy (AAN) is a rapidly progressive renal disease caused by the ingestion of plant products containing aristolochic acid (AA), first described in connection with the use of Chinese herbal medicines. Although the true worldwide extent of this disease is unknown, it is likely to represent a significant cause of chronic kidney disease (CKD) in many parts of the world. Furthermore, recent data have also demonstrated that AA is also the primary aetiological agent in Balkan endemic nephropathy. AAN is notable in its association with urothelial malignancy, with the mechanisms of carcinogenesis now well characterized. Aside from a possible role for corticosteroid therapy in slowing disease progression in selected patients, no disease-specific treatments have yet been shown to alter the course of this nephropathy. Therefore, prevention of exposure to AA and, in affected patients, effective management of the risk of malignancy are key principles in the approach to this condition. Although preparations containing Aristolochia spp. and herbs that can be confused or substituted for Aristolochia have been banned in many countries, other herbal products containing AA have continued to be available to consumers long after these bans have been instituted, highlighting the ongoing need for awareness of this disease.

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