New molecular and field evidences for the implication of mycotoxins but not aristolochic acid in human nephropathy and urinary tract tumor

Pfohl‐Leszkowicz, Annie; Tozlovanu, Mariana; Manderville, Richard A.; Peraica, Maja; Castegnaro, M.; Stefanovic, V.

doi:10.1002/mnfr.200700045

Cited by 130 publications

(105 citation statements)

References 42 publications

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“…Until now, exposure to AA has been associated with the slimming regimen in young women in many highly developed countries, while EN has been the disease of the elderly rural population of both sexes. This suggests that the involvement of AA in the development of EN is not likely, which has also been concluded by Pfohl-Leszkowicz et al (41).…”

Section: Discussionsupporting

confidence: 77%

“…Instead, these and the tissues of surgically removed kidney, urothelial or tumor tissues of patients with AAN in Belgium contained only AA-DNA adducts (40). In a recently published paper OTA-and citrinin-DNA adducts were detected in the tumour kidney tissues of patients with EN from Croatia, Bulgaria, and Serbia, but AA-DNA adducts were not (41).…”

Section: Ota-dna Aa-dna Adducts and P53 Mutations In En And Aanmentioning

confidence: 94%

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Mycotoxic and Aristolochic Acid Theories of the Development of Endemic Nephropathy

Peraica¹,

Domijan²,

Šarić³

2008

Archives of Industrial Hygiene and Toxicology

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Despite many efforts of scientists and epidemiologists, the aetiology of endemic nephropathy (EN) is still unknown. This disease occurs in the rural population of geographically limited areas of Bulgaria, Bosnia and Herzegovina, Croatia, Romania, and Serbia, and a number of theories have been proposed about its aetiology. The mycotoxin theory has prevailed until now, based on the studies of nephrotoxic mycotoxin ochratoxin A (OTA) that revealed higher frequency of OTA-positive food and blood samples in endemic than in non-endemic areas. However, a new aristolochic acid (AA) theory of EN origin has been proposed recently, due to the histological similarities in kidney lesions between patients suffering from EN and patients suffering from Chinese herbs nephropathy caused by AA. Until now it has not been unequivocally proved that the inhabitants of EN areas are exposed to higher concentration of AA than in other regions and the exposure pathways are rather uncertain. This paper presents most important studies supporting both theories, indicating also the inconsistencies of each.

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Section: Discussionsupporting

confidence: 77%

Section: Ota-dna Aa-dna Adducts and P53 Mutations In En And Aanmentioning

confidence: 94%

Mycotoxic and Aristolochic Acid Theories of the Development of Endemic Nephropathy

Peraica¹,

Domijan²,

Šarić³

2008

Archives of Industrial Hygiene and Toxicology

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“…AFs and their metabolite M1 in cow's milk are true hepatocarcinogens (group 1A, IARC, 22), while FBs and OTA are proven nephrotoxins and carcinogens in animals (group 2B, IARC, 22, 23). Some studies suggest that OTA is associated with urinary tract tumours in the EN region, but this effect is still under debate (24). The carcinogenicity of ZEA has not been established, and IARC has classified it in group 3 (25).…”

Section: Discussionmentioning

confidence: 99%

Co-occurrence of Aflatoxins, Ochratoxin A, Fumonisins, and Zearalenone in Cereals and Feed, Determined by Competitive Direct Enzyme-Linked Immunosorbent Assay and Thin-Layer Chromatography

Klarić

Cvetnić

Pepeljnjak

et al. 2009

Archives of Industrial Hygiene and Toxicology

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Aspergillus, Penicillium, and Fusarium species frequently contaminate crops. For this reason mycotoxins such as afl atoxins (AFs), ochratoxin A (OTA), fumonisins (FBs), and zearalenone (ZEA) are found in food and feed in a wide range of concentrations, depending on environmental and storage conditions. Consumption of mycotoxin-contaminated food and feed has been associated with acute and chronic poisoning and carcinoma. The aim of this study was to determine the incidence and co-occurrence of AFs (B 1 +B 2 +G 1 +G 2 ), OTA, FBs (B 1 +B 2 +B 3 ), and ZEA in 37 samples of cereals and feed randomly collected in 2007 from households of an endemic nephropathy (EN) area in Croatia. The mycotoxins were determined using the competitive direct ELISA test (CD-ELISA) in combination with thin-layer chromatography (TLC). The most frequent mycotoxin was ZEA (92 %, mean 318.3 µg kg -1 ), followed by FBs (27 %, 3690 µg kg -1 ), AFs (24.3 %, 4.6 µg kg -1 ), and OTA (16.2 %, 9.8 µg kg -1 ). Levels of AFs, ZEA, and FBs detected by CD-ELISA signifi cantly correlated with the TLC results. However, only one OTA-positive sample was confi rmed by TLC due to its high limit of detection. The levels of these mycotoxins were below the permissible limit for animal feed. Twenty-nine percent of cereals were contaminated with FBs, OTA, or ZEA in mass fractions above the permissible limit for humans. Co-occurrence of two toxins varied between 4.2 % and 54 % and of three between 4.2 % and 7.6 %. Prolonged co-exposure to AFs, OTA, FBs, and ZEA might increase the risk of various chronic diseases.

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“…The most pronounced foodborne exposure to OTA has been found in the area in Croatia where BEN is prevalent. [40] The associated nephrotoxicity and carcinogenicity of OTA, recently described, make this hypothesis particularly attractive. However, to date, there is no evidence that OTA is responsible for any known kidney disease in humans.…”

Section: Environmentally Induced Diseasementioning

confidence: 99%

Fifty Years of Balkan Endemic Nephropathy: Challenges of Study Using Epidemiological Method

et al. 2009

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Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease associated with urothelial cancer, which affects people living in the alluvial plains along the tributaries of the Danube River. Challenges of studying BEN using the epidemiological method are multiple. The natural history from exposure to occurrence of the disease may take many years. The early stages of BEN are not easily detectable clinically, as the disease is asymptomatic until a significant decline in function occurs, and even then symptoms are usually non-specific. The natural history of BEN is complex, possibly with multiple risk factors operating both at the stage of initiation of renal damage and in its progression. In BEN, genetic susceptibility is due to multiple genes of small effects, gene-gene interactions, and gene-environment interactions of complex nature that are difficult to assess with current study designs. BEN is now kidney disease of the old people, and many risk factors for disease such as smoking, alcohol consumption, obesity, and diabetes could contribute to the kidney damage. Evidence is presented that environmental rather than genetic factors play a decisive role in the etiopathogenesis of BEN. Aristolochic acid, described as a culprit of BEN in 1959, is confirmed in 2007 by the molecular biology methods. Mycotoxins and polycyclic aromatic hydrocarbons, leached from lignites and found in the vicinity of endemic settlements, deserve further investigation. Despite advances in understanding the epidemiology of BEN, more research is needed on the patterns of BEN over time and between places, and on identifying the contributions of modifiable risk factors in initiating and hastening progression of BEN in order to improve the scope for preventing BEN. Primary prevention is still at the beginning. Knowledge accumulated in the fifty years of BEN research and new data about prevention and treatment of chronic kidney disease reveal several effective methods in secondary and tertiary prevention of BEN. Genetic epidemiology could establish the relative size of the genetic effect in relation to other sources of variation in disease risk (i.e., environmental effects such as intrauterine environment, physical and chemical effects, as well as behavioral and social aspects). Public health authorities in the several countries having aristolochic acid nephropathy should take immediate measures for reducing dietary exposure of residents to Aristolochia.

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New molecular and field evidences for the implication of mycotoxins but not aristolochic acid in human nephropathy and urinary tract tumor

Cited by 130 publications

References 42 publications

Mycotoxic and Aristolochic Acid Theories of the Development of Endemic Nephropathy

Mycotoxic and Aristolochic Acid Theories of the Development of Endemic Nephropathy

Co-occurrence of Aflatoxins, Ochratoxin A, Fumonisins, and Zearalenone in Cereals and Feed, Determined by Competitive Direct Enzyme-Linked Immunosorbent Assay and Thin-Layer Chromatography

Fifty Years of Balkan Endemic Nephropathy: Challenges of Study Using Epidemiological Method

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