Relevance of a rat model of papillary necrosis and upper urothelial carcinoma in understanding the role of ochratoxin A in Balkan endemic nephropathy and its associated carcinoma

1992 ◽  
Vol 30 (3) ◽  
pp. 205-211 ◽  
Author(s):  
P.H. Bach ◽  
N.J. Gregg ◽  
L. Delacruz
Keyword(s):  
Urothelial Carcinoma ◽  
Ochratoxin A ◽  
Rat Model ◽  
Balkan Endemic Nephropathy ◽  
Papillary Necrosis ◽  
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.

Karyomegaly of tubular kidney cells in human chronic interstitial nephropathy in Tunisia: respective role of Ochratoxin a and possible genetic predisposition

2004 ◽  
Vol 23 (7) ◽  
pp. 339-346 ◽  
Author(s):  
Wafa Hassen ◽  
Salwa Abid-Essafi ◽  
Abdellatif Achour ◽  
Noureddine Guezzah ◽  
Abdelfettah Zakhama ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Food Samples ◽  
Balkan Endemic Nephropathy ◽  
Unknown Aetiology ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Endemic Nephropathy ◽  
Interstitial Nephropathy ◽  
Renal Tubular

Karyomegalic nephropathy associated to bizarre enlargement of nuclei in renal tubular epithelial cells was first described by Mihatch in 1979. We present herein additional cases occurring in three siblings suffering from chronic interstitial nephropathy (CIN) of unknown aetiology where the renal biopsies showed numerous enlarged and hyperchromatic nuclei. CIN of unknown aetiology has been previously characterized and showed striking similarities with Balkan Endemic Nephropathy (BEN). Ochratoxin A (OTA) is a nephrotoxic mycotoxin suspected to be the causal agent of the BEN as well as the Tunisian CIN of unknown aetiology. OTA is incriminated in the onset of these disclosed cases of karyomegalic nephropathy since high OTA concentrations were found in blood (505.83 ng/ml, 102.63 ng/ml and 1023 ng/ml) and in urine (94.40 ng/ml and 10.18 ng/ml) of two of them. Moreover, we have investigated OTA in blood and urine as well as in food samples of the entire household (21 people). Our findings suggest (i) a link between OTA and the outcome of this karyomegalic nephropathy, and (ii) the possible involvement of a genetic factor since the three cases have the same haplotype B27/35.

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.

scholarly journals Balkan endemic nephropathy: Role of ochratoxins A through biomarkers

2006 ◽  
Vol 50 (6) ◽  
pp. 519-529 ◽  
Author(s):  
Marcel Castegnaro ◽  
Delphine Canadas ◽  
Terry Vrabcheva ◽  
Theodora Petkova-Bocharova ◽  
Ivan N. Chernozemsky ◽  
...  
Keyword(s):  
Balkan Endemic Nephropathy ◽  
Endemic Nephropathy

E-cadherin expression in upper urothelial carcinoma in Balkan Endemic Nephropathy and non-endemic regions

2009 ◽  
Vol 205 (10) ◽  
pp. 682-689 ◽  
Author(s):  
Ljubinka Jankovic Velickovic ◽  
Takanori Hattori ◽  
Milan Visnjic ◽  
Irena Dimov ◽  
Mariola Stojanovic ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Balkan Endemic Nephropathy ◽  
Endemic Nephropathy ◽  
E Cadherin

scholarly journals Association of SOD2 (rs4880) and GPX1 (rs1050450) Gene Polymorphisms with Risk of Balkan Endemic Nephropathy and its Related Tumors

Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 435
Author(s):  
Biljana Dragicevic ◽  
Sonja Suvakov ◽  
Djurdja Jerotic ◽  
Zorica Reljic ◽  
Ljubica Djukanovic ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Balkan Endemic Nephropathy ◽  
Glutathione Peroxidase 1 ◽  
Endemic Nephropathy ◽  
Urothelial Tumors ◽  
Stage Renal Disease ◽  
End Stage ◽  
Superoxide Dismutase 2 ◽  
Carcinoma Risk

Background: Experimental data show that superoxide dismutase 2 (SOD2) is involved in ochratoxin (OTA)-induced nephrotoxicity, whereas clinical data indicate the role of SOD2 rs4880 or glutathione peroxidase 1 (GPX1) rs1050450 polymorphisms in end-stage renal disease and urothelial carcinoma risk, known to be the major complications of Balkan endemic nephropathy (BEN). Therefore, we hypothesized that SOD2 and GPX1 gene polymorphisms would influence the risk of BEN and its associated tumors. Materials and Methods: The study was conducted in 207 BEN patients and 86 controls from endemic areas. Results: Individuals with both copies of variant SOD2 allele, known for lower mitochondrial antioxidant protection, are at a significantly higher BEN risk (OR = 2.6, p = 0.021). No association was observed between GPX1 gene polymorphism and BEN risk. Combining SOD2 and GPX1 genotypes did not alter the risk of BEN development. Regarding the risk of urothelial tumors in BEN patients, none of the polymorphisms studied was significantly associated with the risk of these tumors. Conclusions: Polymorphism in SOD2 rs4880 gene affects the risk of BEN development. Hence, SOD2 genotyping could, together with a panel of other enzymes, be used as a biomarker of susceptibility in BEN areas.

scholarly journals A Journey Through Mitogen-Activated Protein Kinase and Ochratoxin A Interactions

2009 ◽  
Vol 60 (4) ◽  
pp. 449-456 ◽  
Author(s):  
Lada Rumora ◽  
Tihana Grubišić
Keyword(s):  
Protein Kinase ◽  
Ochratoxin A ◽  
Mitogen Activated Protein Kinase ◽  
Balkan Endemic Nephropathy ◽  
Cytotoxic Action ◽  
Extracellular Signal ◽  
Increased Risk ◽  
Mitogen Activated Protein ◽  
Endemic Nephropathy ◽  
A Cell

A Journey Through Mitogen-Activated Protein Kinase and Ochratoxin A InteractionsOchratoxin A (OTA) is a ubiquitous mycotoxin with potential nephrotoxic, carcinogenic, and cytotoxic action. It has been proposed that OTA might be involved in the development of Balkan endemic nephropathy, which is associated with an increased risk of urinary tract tumours, and of other forms of interstitial nephritis. Cell susceptibility to OTA mainly depends on mycotoxin concentrations, duration of exposure, and intracellular molecular and genetic context. OTA can affect a cell by stimulating or inhibiting certain signalling pathways such as mitogen-activated protein kinase (MAPK). Three major mammalian MAPKs have been described: extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. All MAPKs regulate diverse cellular programmes, but in most cases ERKs have been linked to cell survival, while JNKs, and p38 MAPKs have been implicated in cell death by apoptosis. This review looks into OTA-mediated MAPK activation and its effects.

Ochratoxin A in human blood in relation to nephropathy in Tunisia

1995 ◽  
Vol 14 (7) ◽  
pp. 609-614 ◽  
Author(s):  
K. Maaroufi ◽  
A. Achour ◽  
M. Hammami ◽  
M. El May ◽  
AM Betbeder ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Human Blood ◽  
Western Europe ◽  
The Other ◽  
Balkan Endemic Nephropathy ◽  
Mean Values ◽  
The Balkans ◽  
Endemic Nephropathy ◽  
Interstitial Nephropathy

The determination of ochratoxin A (OTA) in human blood in Tunisian populations is underway. The range of conta mination is between 0.7 to 7.8 ng ml-1 for the general popu lation and 12 to 55 ng ml-1 for people suffering from chron ic renal failure. It appears that 21 to 64% of people suffer ing from nephropathy are OTA positive with a detection limit of 1ng ml-1. This situation prompted us to search for possible association of OTA contamination and nephropa thy resembling Balkan endemic nephropathy. The classifi cation of the ill population into chronic interstitial nephropathy (CIN), chronic glomerular nephropathy (CGN), chronic vascular nephropathy (CVN) and others, indicated that the largest is the CIN group which is signifi cantly different from the other groups, and from the con trol (P < 0.005). Furthermore, it presented the highest OTA mean values (25 to 59 ng ml-1) compared with the control, CGN, CVN and other groups (6 to 18 ng ml-1) according to the designated region in Tunisia. The rural population seems to be more exposed to ochratoxins in Tunisia, as has been previously reported in the Balkans and Western Europe. Altogether, these results emphasise that in Tunisia an endemic ochratoxin-related nephropathy is probably occurring.

Ochratoxin A concentrations in food and feed from a region with Balkan Endemic Nephropathy

2002 ◽  
Vol 19 (8) ◽  
pp. 755-764 ◽  
Author(s):  
M. M. Abouzied ◽  
A. D. Horvath ◽  
P. M. Podlesny ◽  
N. P. Regina ◽  
V. D. Metodiev ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Balkan Endemic Nephropathy ◽  
Food And Feed ◽  
Endemic Nephropathy
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