Mechanism of ochratoxin A-induced immunosuppression

Lea, T.; Steien, Karen; Størmer, Fredrik C.

doi:10.1007/bf00707553

Cited by 106 publications

(52 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Bec:lUSC natuml killer cells are involved in the destruction of tumour cells, the ability ofOTA 10 modul:ue the activity of these cells might contribute to its capacity to induce renal lind hcpmic carcinomas. Lea et al (1989) reponef!thal OTA has a potent inhibitory effcct both at the level of Band T lymphocytes.…”

Section: Immunoloxlcltymentioning

confidence: 97%

Effect of cytochrome P450 induction on the metabolism and toxicity of ochratoxin A

Omar

Gelboin

Rahimtula

1996

Biochemical Pharmacology

View full text Add to dashboard Cite

The role of cytochrome P-450 in me stimulation of lipid peroxidation induccd by thc mycotoxin ochratoxin A (OTA) has been investigated. Purified cytochrome P-450 (liB I) could effectively replace EDTA in stimulating lipid pefOxidation in a reconstituted system l'Onsisling of phospholipid vesicles, NADPH-cYlochrome P-450rcduc!ase, FeJ+, EDTA and NADPll, suggesting that it could mediate the transfer of electrons from NADPH to foc3,. Microsomcs isolated from liven of cobalt protoporphyrin IX-treated rllts (in which cytochrome P-450 Wll" depletedj underwent OTA-dependent lipid peroxidation much more slowly tlmn control microsomes.The role of cytochrome P-450 in OTA met.1bolism was also investigated. To dClermine which cytochrome P·450 isoforms are involved in the metabolism ofOTA, we used different cytochrome P-450 inducers to induce the major isofonns of cytochrome 1'-450 in lhe rm liver.Microsomes from these livers were used to investigate their effect on OTA metabolism.Pretreatment ofmts with pregnenolone -16c(·carbonitrile (peN), phenobarbit.ll (PB), 3-ll1cthyl cholanthrene (3MC), and isosafrole (ISF) greatly induced 4(R)-4-0H-OTA fonmllion; 4(5)-4-011-OTA fonnation was also induced after pretreatment with PB, PCN, 3MC and ISr:. INII pretreaunem primarily induced me 4(5) isomer formation, The fonnation of the 4(R) .md 4 (5) isomeri showed significant differences with respect to pH optima, effect of antioKidants ami iron chelators, The 4(R) isomer fonnation showed a pH optimum of 6.0 using microsornes from rJIs treated with 3MC and ISF, and 6.5 using mierosomes from rats treated with PI] :tnd peN and Wi!S not inhibited by antioxidants or iron chelators. In contmst, both the 4(5) isomer fonmllion and lipid pcroxidation showed a pH optimum of 7.0 -7,5 and both activities were highly sensitive to inhibition by antioxidants and iron ehelators. Lipid peroxides were no: involved in the 4(5) isomer fonnation since addition of linoleic acid hydroperoxidc to microsomcs did not give rise 10 the 4(5) isomer, Cytochrome P-450 appeared to be essenlial since other hemoprolcins such as horseradish peroxidase and hemoglobin were ineffective in metabolizing OTA. Microsomes from rats pretreated with Co-protoporphyrin IX resulted in no metabolil,rn of ochratoxin A. 7-Ethoxy-and 7-pentoxyresorufin assays showed specificity towards cytochromes P-450 induced by 3MC (fA I/lA2) and PB (IIBI) respectively. Also, metyrapone (inhibitor of cytochrome P·450 IIBt) preferentially inhibited OTA mel1bolism by microsomes from rats treated with PB, and I(-naphthoflavone (inhibitor of cytochrome P-450 IAI/lA2) preferentially inhibited OTA metabolism by microwmes from 3MC and ISF treated rats_ Monoclonal antibodies (MAbs) 1-7-1 (against P-450 lA 1/lA2) and 2-66-3 (against P-450 liB I) showed preferential inhibition ofOTA metabolism by microsomes from 3MC and PB treated rats respectively.Excretion of renal enzymes in urine is a sensitive non-invasive index of renal dam:lge.Therefore. we examined the effect of cytochrome P-450 induction on the...

show abstract

Section: Immunoloxlcltymentioning

confidence: 97%

Effect of cytochrome P450 induction on the metabolism and toxicity of ochratoxin A

Omar

Gelboin

Rahimtula

1996

Biochemical Pharmacology

View full text Add to dashboard Cite

show abstract

“…OTA also decreases the activity of phosphoenol pyruvate carboxykinase (PEPCK) and reduces the level of renal neoglucogenesis [59]. In addition, OTA inhibits B and T lymphocytes [39].…”

Section: Effects Of Mycotoxins On Ruminant Healthmentioning

confidence: 99%

Mycotoxins in feeds and their fate in animals: a review

2002

View full text Add to dashboard Cite

-Mycotoxins are secondary metabolites secreted by moulds, mostly belonging to the three genera Aspergillus, Penicillium and Fusarium. They are produced in cereal grains as well as forages before, during and after harvest, in various environmental conditions. Due to the diversity of their toxic effects and their synergetic properties, mycotoxins are considered as risky to the consumers of contaminated foods. Mycotoxin metabolism is complex and involves pathways of bioactivation and detoxification in both humans and animals. Detoxification occurs via biotransformation mediated by enzymes in the host cells and in the digestive microbial flora. Some of the toxins or their metabolites may become fixed in animal or human tissues. However, most are eliminated in the urine, faeces and milk. In animals, toxicity is generally revealed as chronic minor troubles and only rarely causes death. The presence of mycotoxins in feeds may decrease feed intake and affect animal performance. In addition, the possible presence of toxic residues in edible animal products (milk, meat, offal), may have some detrimental effects on human health. Maximum acceptable doses in feeds and milk have been set for certain mycotoxins by international authorities. The potential risks of mycotoxins may be controlled by checking plant material for fungal contamination, by improving methods of cultivation, harvest and storage, by eliminating or diluting toxins from the contaminated food or feeds, and by using adsorbents to reduce the bioavailability of toxins in the digestive tracts of animals. These measures will be assessed in the present paper. (0)4 73 63 46 59; e-mail: jouany@clermont.inra.fr présent dans le tube digestif. Certaines des toxines ou de leurs métabolites peuvent être fixés dans les tissus animaux ou humains. Cependant, la majorité est éliminée dans l'urine, dans les fèces et dans le lait. La toxicité se manifeste généralement sous forme de troubles chroniques difficiles à identifier, et rarement par la mort de l'animal. La présence de mycotoxines dans les aliments diminue la plupart du temps les quantités d'aliments ingérés ainsi que les performances zootechniques des animaux. La présence de résidus toxiques dans les produits animaux destinés à la consommation humaine (lait, viande, abats) constitue un risque potentiel qu'il est nécessaire d'évaluer pour mieux répondre à la demande sociétale de sécurité dans la chaîne alimentaire. Des doses acceptables devront être définies pour les toxines les plus dangereuses. En parallèle, des moyens de contrôle devront être mis en place pour vérifier l'innocuité des produits alimentaires mis sur le marché. Le risque potentiel des mycotoxines peut être diminué en évitant la contamination des plantes par les moisissures au moment de leur culture, de leur récolte et de leur conservation. Il est également possible de réduire la concentration en toxines des plantes contaminées par dilution avec des aliments sains et par des traitements appropriés, et (ou) de limiter la biodisponibilité des myc...

show abstract

“…It is also caused by impairment of the antigen processes during phagocytosis [37,41]. Moreover, it induces lymphotoxic activities in cases of ochratoxin A as an effect on lymphocytes [62].…”

Section: Effects On Immune Systemmentioning

confidence: 99%

Evidence Based Phytopharmacological Potential of Herbal Extracts in Post-Ingestion Management of Mycotoxins in Animal Models

RMJ¹

2015

J Clin Toxicol

View full text Add to dashboard Cite

Aflatoxins and ochratoxins are common mycotoxic food poisons and acute doses are responsible for causing liver and kidney damage and hepatocarcinoma. The strategy for managing mycotoxins has mainly been pre-ingestive. However, few solutions have been proposed for post-ingestion management and likewise there is no antidote for managing the condition. Studies have demonstrated that Saccharomyces cerevisiae and herbal extracts have potential of limiting the damage caused by reactive oxygen species and toxic effects associated with mycotoxins. Further evidence also shows that herbal extracts provides protection to a variety of cancer cell lines associated with mycotoxins. This study therefore examines the probable potential and options of using medicinal herbal extracts, on their own or in combinations with Saccharomyces cerevisiae, in the management of mycotoxicosis. A combination of the two has potential to offer a multifunctional approach in the management of post ingested mycotoxins such as aflatoxins and ochratoxins.

show abstract

Mechanism of ochratoxin A-induced immunosuppression

Cited by 106 publications

References 16 publications

Effect of cytochrome P450 induction on the metabolism and toxicity of ochratoxin A

Effect of cytochrome P450 induction on the metabolism and toxicity of ochratoxin A

Mycotoxins in feeds and their fate in animals: a review

Evidence Based Phytopharmacological Potential of Herbal Extracts in Post-Ingestion Management of Mycotoxins in Animal Models

Contact Info

Product

Resources

About