Ochratoxins nephrotoxicity

Ochratoxin A (OTA) is a my cotoxin produced by some species of Penicillium and Aspergillus. It is nephrotoxic to all animal species tested and the causal agent of mycotoxic porcine nephropathy (Krogh, 1978). It was previously associated with the human renal disorder, Balcan endemic nephropathy (BEN), and tumours of the urinary tract (Pfohl-Leszkowicz et al., 2002). Recently, another endemic kidney disease (Tunisian chronic interstitial nephropathy, CIN) was linked to OTA-contaminated food (Creppy, 1999 Wafa et al.,... 

Mycotoxins, selected ochratoxins, trichothecenes, ergot (No. 105,1990) Nephrotoxicity associated with exposure to chemicals, principles and methods for the assessment of (No. 119,1991) Neurotoxicity associated with exposure to chemicals, principles and methods for the assessment of (No. 60,1986) Neurotoxicity risk assessment for human health, principles and approaches (No. 223,2001)... 

Mycotoxins are defined as mould derived secondary metabohtes and include Ochratoxin A (OTA). OTA, produced by Aspergillus ochraeus and Penicillium ver-rucosum, can be found as a contaminant in grain, beer, coffee and meat. OTA is nephrotoxic, hepatotoxic and carcinogenic [197]. 

Luhe A, Fllldebrand FI, Bach U, DlngermannT,and Ahr FIJ. A new approach to studying ochratoxin A(OTA)-lnduced nephrotoxicity expression profiling in vivo and in vitro employing cDNA microarrays.Toxicol Scl 73 315-328, 2003. 

Rached E, Hoffmann D, Blumbach K, et al. Evaluation of putative biomarkers of nephrotoxicity after exposure to Ochratoxin A in vivo and in vitro. Toxicol Sci. 2008 103 371-381. 

Van Egmond H.P. (1991) Methods for determining ochratoxin A and other nephrotoxic mycotoxins. lARC Scientif. Publ., 115, 57-70. 

The ochratoxins are a small family of toxic fungal metabolites originally isolated from Aspergillus ochraceus Wilhelm (ref.82). They have subsequently been reported from other Aspergillus species including A. melleus (ref.83,84) and several species of Penicillium (ref. 85-89). Ochratoxins are Icnown to be nephrotoxic and hepatotoxic whilst ochratoxin A is a teratogen (ref.90). Because... 

Moreover, fungi can synthesize various toxins [148] such as aflatoxins which are powerful hepatocarcinogenic agents produced by Aspergillus flavus, or ochratoxins, which are carcinogenic and nephrotoxic mycotoxins synthesized by Aspergillus ochraceus [149]. 

For this evaluation, the Committee considered new toxicological studies that had become available since the last evaluation these included further studies on developmental toxicity, neurotoxicity, immunotoxicity, nephrotoxicity and geno-toxicity and studies on the mode of action of ochratoxin A in the kidney. The Committee also considered the opinion on ochratoxin A in human food published by the European Food Safety Authority (EFSA) in 2006 (European Food Safety Authority, 2006). New data on analytical methods, sampling protocols and the effects of processing were also considered, together with methods of prevention and control and levels and patterns of food contamination. A new dietary exposure assessment was conducted, and the impact of different MLs for cereals was considered. 

As described in the previous evaluation of ochratoxin A by this Committee (Annex 1, reference 153), the pig appears to be the most sensitive species with respect to the nephrotoxic effects of ochratoxin A, and the LOEL in pigs for renal effects Is the basis of the PTWI. 

The earlier literature on the association between human exposure to ochratoxin A and the occurrence of Balkan endemic nephropathy and associated urinary tract tumours was summarized in the previous evaluation (Annex 1, reference 153. Contrary to the clear causal evidence of ochratoxin A-induced nephrotoxicity and kidney carcinogenicity in rodents, the significance of ochratoxin A for human health remains unclear from the available epidemiological evidence. Moreover, ochratoxin A exposure is only one of several hypotheses concerning an environmental etiology for Balkan endemic nephropathy. 

Kumar, M., Dwivedi, P., Sharma, A.K., Singh, N.D. Patil, R.J. (2007) Ochratoxin A and citrinin nephrotoxicity in New Zealand White rabbits an ultrastmctural assessment. Mycopathologla 163, 21-30. 

Pfohl-Leszkowicz, A., Bartsch, H., Azemar, B., Mohr, U., Esteve, J. Castegnaro, M. (2002) MESNA protects rats against nephrotoxicity but not carcinogenicity induced by ochratoxin A, implicating two separate pathways. Med. Biol. 9, 37—43. 

Ranaldi, G., Mancini, E., Ferruzza, S., Sambuy, Y. Perozzi, G. (2007) Effects of red wine on ochratoxin A toxicity in intestinal Caco-2/TC7 cells. Toxicol. In Vitro 21, 204-210. Rasonyi, T. (1995) Mechanistic Investigations In ochratoxin A induced nephrotoxicity and their relevance for the sex specific renal tumor Induction in rats. Zurich, Switzerland, University of Zurich (Dissertation ETH No. 11343). 

Sauvant, C., Holzinger, H., Mildenberger, S. Gelke, M. (2005a) Exposure to nephrotoxic ochratoxin A enhances collagen secretion in renal proximal tubules. Mol. Nutr. Food Res. 49, 31-37. 

Limonciel, A. and Jennings, P. (2014) A review of the evidence that ochratoxin A is an Nrf2 inhibitor implications for nephrotoxicity and renal carcinogenicity. Toxins 6, 371-379. 

Compound 323 is the most toxic of the ochratoxins and shows neurotoxic, nephrotoxic, teratogenic, hepatotoxic, and immimotoxic properties. Furthermore, in 1993 it was classified as a possible carcinogen to humans by the International Agency for Research on Cancer (261). 

For a nephrotoxic toxin, ochratoxin A (OTA), an ECL biosensor based on DNA aptamer as the recognition element and N-(4-aminobutyl)-N-ethylisoluminol... 

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