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«Suspects» in Etiology of Endemic Nephropathy: Aristolochic Acid versus Mycotoxins

By Stjepan Pepeljnjak and Maja Šegvić Klarić

Abstract

Despite many hypotheses that have been challenged, the etiology of endemic nephropathy (EN) is still unknown. At present, the implications of aristolochic acid (AA) and mycotoxins (ochratoxin A—OTA and citrinin—CIT) are under debate. AA-theory is based on renal pathohistological similarities between Chinese herbs nephropathy (CHN) and EN, findings of AA-DNA adducts in EN and in patients with urinary tract tumors (UTT), as well as the domination of A:T®T:A transversions in the p53 mutational spectrum of UTT patients, which corresponds with findings of such mutations in AA-treated rats. However, exposure pathways of EN residents to AA are unclear. Experimental studies attempting to deduce whether nephrotoxins OTA and CIT appear at higher frequencies or levels (or both) in the food and blood or urine of EN residents support the mycotoxin theory. Also, some molecular studies revealed the presence of OTA-DNA adducts in the renal tissue of EN and UTT patients. In this review, data supporting or arguing against AA and mycotoxin theory are presented and discussed

Topics: Review
Publisher: MDPI
OAI identifier: oai:pubmedcentral.nih.gov:3153240
Provided by: PubMed Central

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Citations

  1. (2004). An overview of mycotoxins and toxigenic fungi in Croatia.
  2. (2002). Analgesic nephropathy, Balkan endemic nephropathy and Chinese herbs nephropathy: separate tubulointerstitial kidney diseases associated with urothelial malignancy. Facta Universitatis
  3. (2001). Analyses of DNA adducts formed by ochratoxin A and aristolochic acid in patients with Chinese herbs nephropathy.
  4. (2003). Analysis for DNA adducts, ochratoxin A content and enzyme expression in kidneys of pigs exposed to mild experimental chronic ochratoxicosis. Facta Universitatis
  5. (2002). Analysis of ochratoxin A in serum and urine of inhabitants from an area with Balkan endemic nephropathy: A one month follow up study. Facta Universitatis
  6. (2007). Aristolochic acid and the etiology of endemic (Balkan) nephropathy.
  7. (2007). Aristolochic acid mutagenesis: molecular clues to the etiology of Balkan endemic nephropathy-associated urothelial cancer. Carcinogenesis
  8. Aristolochic acid: a toxicological review.
  9. (2002). Balkan endemic nephropathy and associated urinary tract tumors: a review on aetiological causes and the potential role of mycotoxins.
  10. Binding of ochratoxin A to a urinary globulin: a new concept to account for gender difference in rat nephrocarcinogenic responses.
  11. (2008). Biotransformation enzymes in development of renal injury and urothelial cancer caused by aristolochic acid. Kidney Int.
  12. (1998). Chinese herbs nephropathy associated slimming regimen induces tumors in the forestomach but no interstitial nephropathy in rats.
  13. (2001). Chronic aristolochic acid toxicity in rabbits: a model of Chinese herbs nephropathy? Kidney Int.
  14. (2009). 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.
  15. (2000). Co-occurrence of ochratoxin A and citrinin in cereals from bulgarian villages with a history of Balkan endemic nephropathy.
  16. (2004). Combined toxic effects of mycotoxins.
  17. (2008). Combined toxic effects of ochratoxin A and citrinin, in vitro and in vivo. In Food Contaminats; Mycotoxins & Food Allergen; Siantar,
  18. (1982). Contamination with molds and occurrence of ochratoxin A in smoked meat products from endemic nephropathy region of Yugoslavia.
  19. (2006). Critical evaluation of environmental exposure agents suspected in the etiology of Balkan endemic nephropathy.
  20. (2008). Cytotoxicity and apoptosis induced by fumonisin B1, beauvericin and ochratoxin A in porcine kidney PK15 cells: effects of individual and combined treatment. Arch Toxicol.
  21. (2005). Endemic nephropathy: the case for chronic poisoning by Aristolochia.
  22. (2006). Etiology of Balkan endemic nephropathy and associated urothelial cancer.
  23. (1974). Experimental porcine nephropathy changes of renal functiun and structure induced by ochratoxin A-contaminated feed.
  24. (2005). Genetic polymorphisms of cytochrome P450 among patients with Balkan endemic nephropathy
  25. (2006). Genetic studies in BEN and associated urothelial cancers.
  26. genotoxicity and apoptosis induced by ochratoxin A and citrinin in porcine kidney PK15 cells: effects of single and combined mycotoxins.
  27. (2008). Genotoxicity of fumonisin B1, beauvericin and ochratoxin A in porcine kidney PK15 cells: effects of individual and combined treatment.
  28. (2006). Germline p53 single-base changes associated with Balkan endemic nephropathy.
  29. (2006). Glutathione S-transferaze polymorphisms and ochratoxin A toxicity in primary human urothelial cells. Toxicology
  30. (2010). Health risk assessment of ochratoxin A for all age-sex strata in a market economy. Food Addit. Contam.
  31. (2001). High-performance liquid chromatographic determination of sphinaganine and sphingosine in serum and urine of subjects from an endemic nephropathy area in
  32. (2002). Human and experimental features of aristolochic acid nephtopathy (AAN; formerly Chinese herbs nephropathy-CHN): are they relevant to Balkan endemic nephropathy (BEN)? Facta Universitatis
  33. (2006). Human sulphotransferases are involved in the activation of aristolochic acids and are expressed in renal target tissue.
  34. (1994). Identification of aristolochic acid in Chinese herbs. Lancet
  35. (2004). Karyomegaly of tubular kidney cells in human chronic interstitial nephropathy in Tunisia: respective role of ochratoxin A and possible genetic predisposition.
  36. (2007). Lipid peroxidation and glutathione levels in porcine kidney PK15 cells after individual and combined treatment with fumonisin B1, beauvericin and ochratoxin
  37. (2005). Mold contamination and co-occurrence of mycotoxins in corn grain in Croatia. Acta Pharm.
  38. (2008). Mycotoxic and aristolohic acid theories of the developement of endemic nephropathy.
  39. (2007). New molecular and field evidences for the implication of mycotoxins but not aristolochic acid in human nephropathy and urinary tract tumor. Mol. Nutr. Food Res.
  40. (2009). Ochratoxin A and aristolochic acid involvement in nephropathies and associated urothelial tract tumors.
  41. (1999). Ochratoxin A and fumonisins (B1 and B2) in corn from Balkan nephropathy endemic and non endemic areas of Croatia.
  42. (1991). Ochratoxin A and other mycotoxins in cereals from an area of Balkan endemic nephropathy and urinary tract tumors in Bulgaria.
  43. (2007). Ochratoxin A as a potential etiologic factor in endemic nephropathy: Lessons from toxicity studies in rats. Food Chem. Toxicol.
  44. (2001). Ochratoxin A in corn and wheat: geographical association with endemic nephropathy.
  45. (1997). Ochratoxin A in human sera in the area with endemic nephropathy in
  46. (2007). Ochratoxin A: an overview on toxicity and carcinogenicity in animals and humans.
  47. (2009). p53 mutations as fingerprints for aristolochic acid–an environmental carcinogen in endemic (Balkan) nephropathy.
  48. (2005). Perspective: Ochratoxin A is not a genotoxic carcinogen.
  49. (1993). Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet
  50. (2005). Recent data on Endemic nephropathy and related urothelial tumors in Croatia.
  51. (2007). Role of exposure analysis in solving the mystery of Balkan endemic nephropathy.
  52. (2005). Seed-borne fungi and ochratoxin A contamination of dry beans (Phaseolus vulgaris L.) in the Republic of Croatia. Food Chem. Toxicol.
  53. (1998). Sex and strain differences in ochratoxin A metabolism and DNA adduction in two strains of rats.
  54. (1998). Sex and strain-specific induction of renal tumors by ochratoxin A rats correlates with DNA adduction.
  55. (1995). Školska Knjiga:
  56. (2006). Standard and Fpg-modified comet assay in kidney cells of ochratoxin A- and fumonisin B1-treated rats. Toxicology
  57. Structures of covalent adducts between DNA and ochratoxin A: A new factor in debate about genotoxicity and human risk assessment.
  58. (2010). Studies on carcinogenic and toxic effects of OTA in chicks. Toxins
  59. (2004). Synergistic effects of fumonisn B1 and ochratoxin A: arein vitro cytotoxicity data predictive of in vivo acute toxicity? Toxicology
  60. (2008). The involvement of mycotoxins in the development of endemic nephropathy.
  61. (1985). The mycotoxicological chain and contamination of food by ochratoxin A in Yugoslavia. Mycopathologia
  62. (1999). The occurrence of ochratoxin A
  63. (1988). Tumor induction in mice following exposure to aristolochic acid.
  64. (2000). Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia
  65. (2001). Variations of ochratoxin A concentration in the blood of healthy populations in some Croatian cities.