Comparative rates of hydrolysis of ochratoxins A and B in vitro

Doster, R.C.; Sinnhuber, R. O.

doi:10.1016/s0015-6264(72)80257-8

Cited by 53 publications

(29 citation statements)

References 7 publications

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“…First, male rats generate higher levels of GSHconjugates than female rats, suggesting a greater level of OTA bioactivation, which is required for DNA adduction (13,14) and probably in vivo mutagenicity (12). Second, much higher levels of OTa are detected in the liver ( Figure 6A) compared to the kidney ( Figure 7A) and formation of OTα is a detoxifi cation pathway for OTA (24)(25)(26), suggesting greater sensitivity of the kidney to OTA. At present, the GSH-conjugates of OTA in rat liver and kidney were characterised by HPLC with fl uorescence detection using authentic samples for comparison.…”

Section: Discussionmentioning

confidence: 99%

“…The nonchlorinated OTB derivative undergoes hydrolysis by carboxypeptidase A at a faster rate than OTA (24,25) and this has been invoked as a rationale for the lower toxicity of the OTB analog (26). The nontoxic OTα has previously been detected as the major OTA metabolite in human blood and urine samples (27) and may serve as a sensitive biomarker for OTA exposure (28).…”

Section: Abstract: Bioactivation Carcinogenicity Dna Adduction Glmentioning

confidence: 99%

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Glutathione Conjugates of Ochratoxin a as Biomarkers of Exposure / Glutationski Konjugati Okratoksina A Kao Biomarkeri Izloženosti

Tozlovanu

Canadas

Pfohl‐Leszkowicz

et al. 2012

Archives of Industrial Hygiene and Toxicology

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In the present study the photoreactivity of the fungal carcinogen ochratoxin A (OTA) has been utilised to generate authentic samples of reduced glutathione (GSH) and N-acetylcysteine (NAC) conjugates of the parent toxin. These conjugates, along with the nontoxic OTα, which is generated through hydrolysis of the amide bond of OTA by carboxypeptidase A, were utilised as biomarkers to study the metabolism of OTA in the liver and kidney of male and female Dark Agouti rats. Male rats are more susceptible than female rats to OTA carcinogenesis with the kidney being the target organ. Our studies show that the distribution of OTA in male and female rat kidney is not signifi cantly different. However, the extent of OTA metabolism was greater in male than female rats. Much higher levels of OTα were detected in the liver compared to the kidney, and formation of OTα is a detoxifi cation pathway for OTA. These fi ndings suggest that differences in metabolism between male and female rats could provide an explanation for the higher sensitivity of male rats to OTA toxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Abstract: Bioactivation Carcinogenicity Dna Adduction Glmentioning

confidence: 99%

Glutathione Conjugates of Ochratoxin a as Biomarkers of Exposure / Glutationski Konjugati Okratoksina A Kao Biomarkeri Izloženosti

Tozlovanu

Canadas

Pfohl‐Leszkowicz

et al. 2012

Archives of Industrial Hygiene and Toxicology

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“…The significance of such proposed binding is unknown but may be involved in its potent nephrotoxicity. Others have suggested that the rate of hydrolysis of ochratoxin A may partially explain its toxicity since the in vitro enzymatic hydrolysis of ochratoxin A is much slower than that of ochratoxin B [8].…”

Section: Discussionmentioning

confidence: 99%

Ochratoxicosis in Beagle Dogs. II. Pathology

1973

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(With 1 color plate)Absruact. The gross lesions in 23 young male Beagle dogs given daily oral doses of 0.2-3.0 nig/kg body weight ochratoxin A consisted of moderate to severe niucohemorrhagic enteritis of the cecum, colon, and rectum; tonsillitis; and enlargement of lymph nodes, which were edematous, hyperemic, and focally necrotic. Histopathologic alterations in the kidneys consisted of necrosis and desquamation of epithelial cells mainly in, but not limited to, proximal convoluted tubules. Many proximal and distal convoluted tubules contained eosinophilic, granular casts. Necrosis of lymphoid tissues was a prominent feature of the niycotoxicosis and focally occurred in, but was not limited to, germinal centers in the spleen, tonsils, thymus, and lymph nodes and the lymphoid nodules of the jejunum, ileum, cecum, colon, rectum and nictitating membrane. Necrosis did not occur in bone marrow. Hepatic alterations consisted of slight to moderate centrilobular necrosis and fatty change and occurred mainly in dogs receiving 0.2-0.3 mg/kg body weight ochratoxin A daily for 11-14 days.In a companion paper [30], we described the clinical and clinicopathologic features of ochratoxicosis in Beagle dogs. Ochratoxins, the principal one of which is ochratoxin A, are fungal metabolites first isolated from Aspergillus ochraceus [33] and later identified as metabolites of Penicillium viridicatum [34] and other members of the A . ochraceus group [13, 191. The pathologic changes produced by ochratoxin A have been studied in the duckling [26,32], rat [23, 25, 27, 28, 321, chick [3, 10, 241 and trout 191. In the species studied, ochratoxicosis is characterized by renal and hepatic damage and alterations in the intestinal and lymphoid tissues. The severity of the lesions varies somewhat with species and dose of ochratoxin.The present report describes the gross and microscopic pathologic alterations produced in dogs by either an ochratoxin-A-containing rice culture of A . ochraceus or commercial ochratoxin A.

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“…Both characteristics appear somewhat reflected in the molecule structure of OTA. In fact, historically carboxypeptidase A was the first enzyme shown to be effective in OTA degradation [75,76,77], and is still used as a standard for activity of OTA degrading enzymes [67]. …”

Section: Degradation Of Ochratoxin a In Ruminantsmentioning

confidence: 99%

Ochratoxin A in Ruminants–A Review on Its Degradation by Gut Microbes and Effects on Animals

Mobashar

Hummel

Blank

et al. 2010

Toxins

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Ruminants are much less sensitive to ochratoxin A (OTA) than non-ruminants. The ruminal microbes, with protozoa being a central group, degrade the mycotoxin extensively, with disappearance half lives of 0.6–3.8 h. However, in some studies OTA was detected systemically when using sensitive analytical methods, probably due to some rumen bypass at proportions of estimated 2–6.5% of dosage (maximum 10%). High concentrate proportions and high feeding levels are dietary factors promoting the likeliness of systemic occurrence due to factors like shifts in microbial population and higher contamination potential. Among risk scenarios for ruminants, chronic intoxication represents the most relevant.

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Comparative rates of hydrolysis of ochratoxins A and B in vitro

Cited by 53 publications

References 7 publications

Glutathione Conjugates of Ochratoxin a as Biomarkers of Exposure / Glutationski Konjugati Okratoksina A Kao Biomarkeri Izloženosti

Glutathione Conjugates of Ochratoxin a as Biomarkers of Exposure / Glutationski Konjugati Okratoksina A Kao Biomarkeri Izloženosti

Ochratoxicosis in Beagle Dogs. II. Pathology

Ochratoxin A in Ruminants–A Review on Its Degradation by Gut Microbes and Effects on Animals

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