Analysis of Polycyclic Aromatic Hydrocarbons and Phthalate Esters in Soil and Food Grains from the Balkan Peninsula: Implication on DNA Adduct Formation by Aristolochic Acid I and Balkan Endemic Nephropathy

2021 ◽  
Author(s):  
Wanlin Guo ◽  
Jiayin Zhang ◽  
Zhihan Sun ◽  
William H. Orem ◽  
Calin A. Tatu ◽  
...  
Keyword(s):  
Aristolochic Acid ◽  
Phthalate Esters ◽  
Balkan Peninsula ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Balkan Endemic Nephropathy ◽  
Food Grains ◽  
Polycyclic Aromatic ◽  
Endemic Nephropathy ◽  
Aristolochic Acid I

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 Ochratoxin A and Aristolochic Acid Involvement in Nephropathies and Associated Urothelial Tract Tumours

2009 ◽  
Vol 60 (4) ◽  
pp. 465-483 ◽  
Author(s):  
Annie Pfohl-Leszkowicz
Keyword(s):  
Ochratoxin A ◽  
Aristolochic Acid ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Balkan Endemic Nephropathy ◽  
Aristolochic Acids ◽  
The World ◽  
Main Culprit ◽  
Endemic Nephropathy

Ochratoxin A and Aristolochic Acid Involvement in Nephropathies and Associated Urothelial Tract TumoursThis review addresses the unresolved aetiology of several nephropathies and associated upper tract tumours diagnosed all over the world, but especially in the Balkan regions. Studies conducted over the last 35 years point to mycotoxins, mainly ochratoxin A (OTA) as the main culprit. Recent theories however have implicated aristolochic acids (AA). The aim of this review is to put forward arguments in favour of the mycotoxin theory and to show the incoherence of the AA theory. It discusses the differences between the epidemiology of Balkan endemic nephropathy (BEN) and aristolochic acid nephropathy (AAN); OTA and AA carcinogenicity; clinical and pathological effects induced by OTA and AA; sources of OTA contamination (food, air, drinking water); OTA- and AA-DNA adduct formation; the role of genetic polymorphisms; and the risk for young children.

DNA adduct formation of aristolochic acid I and II in vitro and in vivo

1988 ◽  
Vol 9 (2) ◽  
pp. 297-303 ◽  
Author(s):  
H.H. Schmeiser ◽  
K.-B. Schoepe ◽  
M. Wiessler
Keyword(s):  
Aristolochic Acid ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Aristolochic Acid I

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

scholarly journals Comparison of Aristolochic acid I derived DNA adduct levels in human renal toxicity models

Toxicology ◽  
2019 ◽  
Vol 420 ◽  
pp. 29-38 ◽  
Author(s):  
Heinke Bastek ◽  
Tabea Zubel ◽  
Kerstin Stemmer ◽  
Aswin Mangerich ◽  
Sascha Beneke ◽  
...  
Keyword(s):  
Aristolochic Acid ◽  
Renal Toxicity ◽  
Dna Adduct ◽  
Aristolochic Acid I

Exposure-route-dependent DNA adduct formation by polycyclic aromatic hydrocarbons

2000 ◽  
Vol 21 (1) ◽  
pp. 87-92 ◽  
Author(s):  
Roger W.L. Godschalk ◽  
Edwin J.C. Moonen ◽  
Pauline A.E.L. Schilderman ◽  
Wendy M.R. Broekmans ◽  
Jos C.S. Kleinjans ◽  
...  
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Aromatic Hydrocarbons ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Exposure Route ◽  
Polycyclic Aromatic

The influence of ochratoxin A on DNA adduct formation by the carcinogen aristolochic acid in rats

2014 ◽  
Vol 89 (11) ◽  
pp. 2141-2158 ◽  
Author(s):  
Marie Stiborová ◽  
František Bárta ◽  
Kateřina Levová ◽  
Petr Hodek ◽  
Eva Frei ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Aristolochic Acid ◽  
Adduct Formation ◽  
Dna Adduct
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