Pharmacokinetics of ochratoxin A and its metabolites in rats.

doi:10.1006/TAAP.1997.8155

Paper

Pharmacokinetics of ochratoxin A and its metabolites in rats.

Published Jul 1, 1997 · S. Li, R. R. Marquardt, A. Frohlich

Toxicology and applied pharmacology

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127

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9

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Abstract

Ochratoxin A (OA) is a mycotoxin that is produced on moist grain. It is commonly found in the blood of swine in western Canada and is a potent nephrotoxic, carcinogen, and immunosuppressive agent. The pharmacokinetic characteristics of six analogs of OA including OA, OB (OA without chloride), OC (OA ethyl ester), and some metabolites, such as O alpha (OA without phenylalanine), OA-OH (hydroxylated OA), and a newly discovered form of OA, OP-OA (lactone opened ring of OA), were investigated in rats after a single intravenous administration of the compounds. All of the ochratoxin analogs were distributed following a two compartment open model. The elimination half-lives of OA, OP-OA, O alpha, OA-OH, OB, and OC were 103+/-16, 50.5+/-2.8, 9.6+/-2.3, 6+/-0.9, 4.2+/-1.2, and 0.6+/-0.2 hr, respectively. Total body clearance of OA, OP-OA, O alpha, OA-OH, and OB via the bile, urine, and metabolic routes were 3.1, 3.6, 40, 65, and 43 ml/hr kg, respectively. OA, OB, and O alpha were mainly cleared in the urine (> or = 48%), OA-OH in the bile (41%), and OP-OA as metabolites (43%). Metabolism accounted for 43, 44, 33, and 29% of the total clearance of OA, O alpha, OA-OH, and OB, respectively. It is concluded that OA has a long half-life and is very slowly cleared from the body and that its metabolites are cleared at a much faster rate with much shorter half-lives. Procedures should be devised to enhance the conversion in the body of OA to O alpha, OA-OH, or other metabolites as this would shorten its half-life and therefore its toxicity.

Non-RCT

Animal Study

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Key takeawayOchratoxin A has a long half-life and is slowly cleared from the body, while its metabolites are cleared at a faster rate with shorter half-lives, suggesting a need for procedures to enhance conversion to reduce toxicity.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Pharmacokinetics of ochratoxin A and its metabolites in rats.

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References

Toxicity of ochratoxin A, its opened lactone form and several of its analogs: structure-activity relationships.

The toxicity of ochratoxin A is attributed to its isocoumarin moiety and may involve the lactone carbonyl group, but not directly related to its phenolic hydroxyl group or iron-chelating properties.

Metabolites of ochratoxins in rat urine and in a culture of Aspergillus ochraceus

Fungi can produce some of the same ochratoxin A metabolites as rats, and O alpha, OA, and OC may be covalently linked to fungal macromolecules.

Toxicokinetics of ochratoxin A in rat following intratracheal administration.

Ochratoxin A has a high bioavailability of 98%, a 127-hour biological half-life, and a 0.92 ml/kg.h. plasma clearance in rats after intratracheal administration.

Synthesis and structural elucidation of analogs of ochratoxin A

Synthesis of ochratoxin A analogs from OA or O is efficient and yields high-quality compounds, useful for understanding the structure-activity relationship and for metabolic and immunological studies.

A review of recent advances in understanding ochratoxicosis.

Ochratoxin A contamination in cereal food and feed can occur, but proper storage conditions, adsorbents, and antioxidants can help minimize its harmful effects.

Citations