Evidence for an enterohepatic circulation of ochratoxin A in mice

Roth, Angelika; Chakor, Kheira; EkuéCreepy, Edmond; Kane, Amadou; Röschenthaler, R.; Dirheimer, G.

doi:10.1016/0300-483x(88)90110-2

Cited by 81 publications

(45 citation statements)

References 17 publications

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“…Sreemannarayana and co-workers (1988) observed a single protracted secondary peak in their analysis of serum OTA concentrations in calves following oral OTA administration and suggested this to be due to a superimposition of biliary OTA recycling on the overall elimination process. Similar observations have been made by other authors in rats and mice (Fuchs and Hult 1992, Fuchs et al 1988, Roth et al 1988. The reabsorption of OTA by the kidney has also been proposed to facilitate the residual persistence of the toxin and hence the observed renal toxicity in rodents (Albassam et al 1987, Stein et al 1985.…”

Section: Kinetic Studiessupporting

confidence: 75%

Ochratoxin A: Comparative pharmacokinetics and toxicological implications (experimental and domestic animals and humans)

Dietrich

Heussner

O'Brien

2005

Food Additives & Contaminants

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The causal factors for the species-and sex-differences associated with ochratoxin-mediated toxicity remain unclear. Variations in kinetic parameters may play a major role in explaining these differences, however, discrepancies and inaccuracies in the toxicokinetics reported in the literature for various species, make comparison and hence the extrapolation to the human situation impossible. The one-and two-compartment open models currently proposed may be insufficient to enable an accurate representation of the actual situation in vivo. It is likely that at least three if not four compartments must be assumed to account for the reported effects. The application of such models to existing raw data would most likely provide for a more accurate base set of toxicokinetic data and contribute to a more accurate human risk assessment. Possible explanations for the reported inconsistencies and their impact on the proposed mechanism(s) of action of OTA and risk assessment are discussed.

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Section: Kinetic Studiessupporting

confidence: 75%

Ochratoxin A: Comparative pharmacokinetics and toxicological implications (experimental and domestic animals and humans)

Dietrich

Heussner

O'Brien

2005

Food Additives & Contaminants

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“…Similar observations have been made by other authors in rats and mice. 58,74,75 The reabsorption of OTA by the kidney has also been proposed to facilitate the residual persistence of the toxin and hence the renal toxicity in rodents. 76,77 In vivo metabolism of OTA in a number of species including rodents 78 and ruminants 79 has been shown to predominantly yield the nontoxic congener ochratoxin-α, that is, the isocumarin moiety lacking the phenylalanine group (Figure 1).…”

Section: Protein Binding and Kineticsmentioning

confidence: 99%

Ochratoxin A: The Continuing Enigma

O'Brien

Dietrich

2005

Critical Reviews in Toxicology

359

212

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The mycotoxin ochratoxin A (OTA) has been linked to the genesis of several disease states in both animals and humans. It has been described as nephrotoxic, carcinogenic, teratogenic, immunotoxic, and hepatotoxic in laboratory and domestic animals, as well as being thought to be the probable causal agent in the development of nephropathies (Balkan Endemic Nephropathy, BEN and Chronic Interstitial Nephropathy, CIN) and urothelial tumors in humans. As a result, several international agencies are currently attempting to define safe legal limits for OTA concentration in foodstuffs (e.g., grain, meat, wine, and coffee), in processed foods, and in animal fodder. In order to achieve this goal, an accurate risk assessment of OTA toxicity including mechanistic and epidemiological studies must be carried out. Ochratoxin has been suggested by various researchers to mediate its toxic effects via induction of apoptosis, disruption of mitochondrial respiration and/or the cytoskeleton, or, indeed, via the generation of DNA adducts. Thus, it is still unclear if the predominant mechanism is of a genotoxic or an epigenetic nature. One aspect that is clear, however, is that the toxicity of OTA is subject to and characterized by large species-and sex-specific differences, as well as an apparently strict structure-activity relationship. These considerations could be crucial in the investigation of OTA-mediated toxicity. Furthermore, the use of appropriate in vivo and in vitro model systems appears to be vital in the generation of relevant experimental data. The intention of this review is to collate and discuss the currently available data on OTA-mediated toxicity with particular focus on their relevance for the in vivo situation, and also to suggest possible future strategies for unlocking the secrets of ochratoxin A.

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“…This has been demonstrated for OTA in mice (Roth et al, 1988). One enzyme that could be involved in this process is the β-glucuronidase which is produced by intestinal bacteria.…”

Section: Excretionmentioning

confidence: 81%

Ochratoxin A kinetics: A review of analytical methods and studies in rat model

Vettorazzi

González-Peñas

Ceráin

2014

Food and Chemical Toxicology

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Ochratoxin A (OTA) is a thermostable mycotoxin that contaminates a great variety of foodstuffs. It is nephrotoxic in all of the mammalian species tested, being the pig the most sensitive one; among rodents, rats are the most susceptible to OTA carcinogenicity. Kinetics, by studying the absorption, distribution, metabolism and excretion of xenobiotics, is an important tool for the extrapolation of animal toxicity data. The most important kinetic studies performed with OTA in rats have been reviewed, together with the different methods used for OTA quantification in biological matrices. Thirteen studies in Wistar, Sprague-Dawley or F344 rats, using radiolabeled OTA or TLC, HPLC-FLD or HPLC-MS have been summarized. Very often methods validated for food have been directly applied to tissues. Strain, sex and age differences have been detected but the interpretation is difficult due to the different experimental conditions, and the connection of the several factors that may account for these differences.

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Evidence for an enterohepatic circulation of ochratoxin A in mice

Cited by 81 publications

References 17 publications

Ochratoxin A: Comparative pharmacokinetics and toxicological implications (experimental and domestic animals and humans)

Ochratoxin A: Comparative pharmacokinetics and toxicological implications (experimental and domestic animals and humans)

Ochratoxin A: The Continuing Enigma

Ochratoxin A kinetics: A review of analytical methods and studies in rat model

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