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.

scholarly journals Is Aristolochic Acid Really the Cause of the Balkan Endemic Nephropathy?

2016 ◽  
Vol 2 (1) ◽  
pp. 9-20 ◽  
Author(s):  
Peter George Mantle ◽  
Diana Herman ◽  
Calin Tatu
Keyword(s):  
Dna Adducts ◽  
Biomedical Research ◽  
Human Exposure ◽  
Aristolochic Acid ◽  
Transitional Cell ◽  
Critical Evaluation ◽  
Causal Agent ◽  
Balkan Endemic Nephropathy ◽  
Aristolochic Acid Nephropathy ◽  
Endemic Nephropathy

In recent years, aristolochic acid has been promoted vigorously as the causal agent of the Balkan endemic nephropathy because of similarities to some other nephropathies, association with DNA adducts and a perception of human exposure via bread. Critical evaluation of the literature exposes flaws in these aspects, and there has been consistent failure of experimental toxicology to mimic either the slow silent bilateral atrophy of the Balkan disease or the transitional cell carcinomas in the upper urothelium. It seems yet premature to promote the curious Balkan disease as aristolochic acid nephropathy without the epidemiological rigour necessary in biomedical research.

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 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 Co-Exposure to Aristolochic Acids I and II Increases DNA Adduct Formation Responsible for Aristolochic Acid I-Mediated Carcinogenicity in Rats

2021 ◽  
Vol 22 (19) ◽  
pp. 10479
Author(s):  
František Bárta ◽  
Alena Dedíková ◽  
Michaela Bebová ◽  
Šárka Dušková ◽  
Jaroslav Mráz ◽  
...  
Keyword(s):  
Plant Extract ◽  
Aristolochic Acid ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Renal Diseases ◽  
Balkan Endemic Nephropathy ◽  
Chemical Research ◽  
Aristolochic Acids ◽  
Endemic Nephropathy

The plant extract aristolochic acid (AA), containing aristolochic acids I (AAI) and II (AAII) as major components, causes aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN), unique renal diseases associated with upper urothelial cancer. Recently (Chemical Research in Toxicology 33(11), 2804–2818, 2020), we showed that the in vivo metabolism of AAI and AAII in Wistar rats is influenced by their co-exposure (i.e., AAI/AAII mixture). Using the same rat model, we investigated how exposure to the AAI/AAII mixture can influence AAI and AAII DNA adduct formation (i.e., AA-mediated genotoxicity). Using 32P-postlabelling, we found that AA-DNA adduct formation was increased in the livers and kidneys of rats treated with AAI/AAII mixture compared to rats treated with AAI or AAII alone. Measuring the activity of enzymes involved in AA metabolism, we showed that enhanced AA-DNA adduct formation might be caused partially by both decreased AAI detoxification as a result of hepatic CYP2C11 inhibition during treatment with AAI/AAII mixture and by hepatic or renal NQO1 induction, the key enzyme predominantly activating AA to DNA adducts. Moreover, our results indicate that AAII might act as an inhibitor of AAI detoxification in vivo. Consequently, higher amounts of AAI might remain in liver and kidney tissues, which can be reductively activated, resulting in enhanced AAI DNA adduct formation. Collectively, these results indicate that AAII present in the plant extract AA enhances the genotoxic properties of AAI (i.e., AAI DNA adduct formation). As patients suffering from AAN and BEN are always exposed to the plant extract (i.e., AAI/AAII mixture), our findings are crucial to better understanding host factors critical for AAN- and BEN-associated urothelial malignancy.

scholarly journals Balkan Endemic Nephropathy and the Causative Role of Aristolochic Acid

2019 ◽  
Vol 39 (3) ◽  
pp. 284-296 ◽  
Author(s):  
Bojan Jelaković ◽  
Živka Dika ◽  
Volker M. Arlt ◽  
Marie Stiborova ◽  
Nikola M. Pavlović ◽  
...  
Keyword(s):  
Aristolochic Acid ◽  
Balkan Endemic Nephropathy ◽  
Causative Role ◽  
Endemic Nephropathy
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