Disease relevance of OCHRATOXIN A

• Among other mechanisms of toxicity, it has been suggested that OA inhibits phenylalanyl-tRNA synthetase (PheRS), thereby reducing protein synthesis [1].
• Structure-activity studies in E. coli strains on ochratoxin A (OTA) and its analogues implicate a genotoxic free radical and a cytotoxic thiol derivative as reactive metabolites [2].
• There was a slight decrease in kidney weight in chukars fed 4 ppm OA; however, the decrease was related to the decrease in body weight produced by the toxin [3].

High impact information on OCHRATOXIN A

• Analysis of ochratoxin A (OTA) in wine by LC/MS and multiple mass spectrometry (MS/MS) permits to confirm the toxin presence without the use of expensive immunoaffinity columns, or time and solvent consuming sample derivatization procedures [4].
• No cytochrome C release from mitochondria could be detected during 24 hours of exposure to OTA or cisplatin [5].
• Intra- and extracellular acidification prevented cells from cell death induced by OTA or cisplatin [5].
• Ochratoxin A (OTA), a fungal mycotoxin, is a high-affinity substrate for several renal secretory organic anion transporters (OATs), and literature suggests that this elimination pathway is the route of entry leading to proximal tubule-targeted toxicity [6].
• Increasing concentrations of albumin markedly reduced uptake of OTA by both Xenopus laevis oocytes expressing OATs 1, 3, and 4 and organic anion-transporting polypeptide 1 [6].

Chemical compound and disease context of OCHRATOXIN A

• Neither preincubation with OB nor simultaneous exposure to non-toxic concentrations of OB together with various concentrations of OA influenced the toxicity of OA [7].
• Feeding OTA at levels of 400 and 800 ppb (groups 2 and 3) significantly decreased the body weight, thymus weight, feed consumption, feed conversion ratio and thyroxine concentration (P < 0.05) [8].

Biological context of OCHRATOXIN A

• Acid hydrolysis of the fluorescent macromolecules resulted in the release of several ochratoxins, including O alpha (80%), OA (2%), and OC (5%), and other unidentified fluorescent compounds but not OB and O beta [9].
• At low concentrations (< 25 microM), treatment with OTA was slightly more toxic, whereas reduction in cell viability was similar at concentrations up to 100 microM [10].
• OTA is poorly metabolized and slowly eliminated, and this may play an important role in OTA toxicity, carcinogenicity, and organ specificity [10].
• Each group was found to contain both toxigenic and nontoxigenic strains, indicating that there is no association between molecular genotypes and the ability to produce OA [11].
• OTA greatly induced apoptosis in this cell line, which is contrary to the effects of most tumor promoters [12].

Anatomical context of OCHRATOXIN A

• For all transporters tested, virtually all mediated OTA uptake was eliminated by an albumin concentration equivalent to 10% of that present in the blood plasma [6].
• In LLC-PK1 cells, a renal cell culture system that retains much of the specific features of the proximal tubule, only minor differences in the extent of cytotoxicity of OTA and OTB were observed [10].
• Heterophils, but not macrophages, isolated from chicks receiving OTA-contaminated diet produced less superoxide anion compared to all other diet groups at d 30 and 40 [13].
• OTA reversibly inhibited GJIC at noncytotoxic doses in the rat liver but not the human kidney cell line [12].
• These results also indicate that the nephrotoxicity of OTA either does not involve GJIC, assuming these epithelial cells play a vital role in kidney physiology, or that a more differentiated kidney cell type is the target for OTA toxicity, of which the role of GJIC remains unknown [12].

Associations of OCHRATOXIN A with other chemical compounds

• RESULTS: Inhibition of the mitochondrial function reduced OTA- or cisplatin-induced cell death and led to considerable lactic acid production and extracellular acidification [5].
• When expressed in Xenopus laevis oocytes, rOat5 mediated the transport of sulfate conjugates of steroids such as estrone-3-sulfate (E(1)S; K(m) = 18.9 +/- 3.9 microM) and dehydroepiandrosterone sulfate (K(m) = 2.3 +/- 0.2 microM) in a sodium-independent manner, in addition to OTA [14].
• After solvent extraction, an anion-exchange column (SAX) was used to fix the acidic mycotoxins (OTA, CIT), whilst the neutral mycotoxins flowing through the SAX column were further purified by filtration on a MycoSep cartridge [15].
• The IC50 was 1.9 microM for OA and 6.2 microM for OB [7].
• It also aimed to survey the presence and amounts of DON, OTA and ZEN in Belgian conventionally and organically produced wheat grain and in wholemeal wheat flours [15].

Gene context of OCHRATOXIN A

• We therefore determined the effects of OTA on GJIC and MAPK in a human kidney and rat liver epithelial cell line [12].
• These variables were explored for OA, OB, CIT using two continuous kidney cell lines (LLC-PK1 and OK) and four cytotoxicity assay endpoints [16].
• The concentrations (mean+/-SD) of FB1, ZEA, and OTA in positive samples were 459.5+/-314.6, 1.70+/-0.80, and 1.40+/-0.55 microg kg-1, respectively, and the concentrations of FB2 in two samples were 68.4 and 3084.0 microg kg-1 [17].
• OA-fed ducklings had normal levels of circulating IgG in their sera and there was a subepithelial migration of IgG-positive cells in the bursa of Fabricius [18].

Analytical, diagnostic and therapeutic context of OCHRATOXIN A

• This PCR assay could contribute to the early and rapid detection of the potential presence of OTA in coffee samples [19].
• The limits of detection in cornmeal determined with the automated array biosensor were 15 and 150 ng/g for OTA and DON, respectively [20].
• Enzyme-linked immunosorbent assays (ELISA) kits are widely used as screening methods for the occurrence of OTA in food [21].
• In other studies, patulin, CPA, OA, SAD and ZEN were degraded at 15 sec, with no by-products detectable by HPLC [22].
• A number of methods, mainly based on liquid chromatography (LC) with fluorescence detection (FD), coupled with immunoaffinity column or solid phase extraction cleanup, have been collaboratively validated and adopted as official standards for OTA determination in a variety of foods, including cereals, coffee, wine and beer [21].

References