Excretion profile of corticosteroids in bovine urine compared with tissue residues after therapeutic and growth-promoting administration of dexamethasone

Ferranti, Carolina; Famele, Marco; Palleschi, Luca; Bozzetta, Elena; Pezzolato, Marzia; Draisci, Rosa

doi:10.1016/j.steroids.2013.05.002

Cited by 14 publications

(14 citation statements)

References 15 publications

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“…Furthermore, considerable impact could be attributed to a different sampling schedule, since the last time point in our previous experiment was at slaughter, which intensified the extremely stressful situation. As was mentioned above, heavy stress conditions apparently favour endogenous PL production that is usually accompanied by an increase in urinary concentrations of F and E (Bertocchi et al 2013;Ferranti et al 2013), while exogenous administration of PL is likely to reduce the production of these main endogenous glucocorticoids. Our results confirm this hypothesis and are enriched with monitoring of the levels of F and E A-ring-reduced metabolites.…”

Section: Methods Validationmentioning

confidence: 87%

“…On the basis of these results and the opinion of the European Reference Laboratory, the Italian Ministry of Health has recently enacted a new disposition: a bovine urine sample is considered non-compliant for PL only when its concentration exceeds 5.0 ppb (Circular of Ministry of Health 2012). Recently, evidence has been provided that veal calves, besides endogenous PL production, revealed remarkable F and E urine concentrations as a response to extremely stressful conditions (Ferranti et al 2013). …”

Section: Methods Validationmentioning

confidence: 99%

“…For this purpose, reference or threshold levels need to be introduced. So far, the metabolic fate of exogenously administered PL is relatively unknown, although some very important studies have been conducted recently (Vincenti et al 2012;Ferranti et al 2013;Nebbia et al 2014). The evident decrease in Aring-reduced F and E metabolites during the course of PL treatment may represent a new approach that would discriminate between exogenous and endogenous PL origin.…”

Section: Methods Validationmentioning

confidence: 99%

“…The effects of administration of synthetic corticosteroids on the urinary profile of F has been investigated in humans in detail (Mazzarino et al 2006). On the other hand, few studies have been devoted to investigate the correlation between natural and administered synthetic corticosteroids in order to identify indirect biomarkers for eventual treatments (Savu et al 1996;Capolongo et al 2007;Vincenti et al 2009Vincenti et al , 2012Ferranti et al 2011Ferranti et al , 2013Nebbia et al 2014). Therefore, a method to identify natural corticosteroid levels in bovines could be an important tool for the control of illicit corticosteroid treatment in livestock production.…”

Section: Introductionmentioning

confidence: 99%

“…Remarkably, not many studies about the concentrations of F and E in bovine urine are present in the literature (Antignac et al 2002;Pavlovic et al 2012;Ferranti et al 2013). In addition, due to their low concentrations, synthetic and/or (pseudo)natural corticosteroids are often not detectable in biological matrices by official methods.…”

Section: Introductionmentioning

confidence: 99%

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HPLC-ESI-MS/MS assessment of the tetrahydro-metabolites of cortisol and cortisone in bovine urine: promising markers of dexamethasone and prednisolone treatment

Chiesa

Panseri

Pavlović

et al. 2016

Food Additives & Contaminants: Part A

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The effects of long-term administration of low doses of dexamethasone (DX) and prednisolone (PL) on the metabolism of endogenous corticosteroids were investigated in veal calves. In addition to cortisol (F) and cortisone (E), whose interconversion is regulated by 11β-hydroxysteroid dehydrogenases (11βHSDs), special attention was paid to tetrahydrocortisol (THF), allo-tetrahydrocortisol (aTHF), tetrahydrocortisone (THE) and allo-tetrahydrocortisone (aTHE), which are produced from F and E by catalytic activity of 5α and 5β-reductases. A specifically developed HPLC-ESI-MS/MS method achieved the complete chromatographic separation of two pairs of diastereoisomers (THF/aTHF and THE/aTHE), which, with appropriate mass fragmentation patterns, provided an unambiguous conformation. The method was linear (r 2 > 0.9905; 0.5-25 ng ml . Recoveries were in range 75-114%, while matrix effects were minimal. The experimental study was carried out on three groups of male Friesian veal calves: group PL (n = 6, PL acetate 15 mg day -1 p.o. for 31 days); group DX (n = 5, 5 mg of estradiol (E2) i.m., weekly, and 0.4 mg day -1 of DX p.o. for 31 days) and a control group (n = 8). Urine was collected before, during (twice) and at the end of treatment. During PL administration, the tetrahydro-metabolite levels decreased gradually and remained low after the suspension of treatment. DX reduced urinary THF that persisted after the treatment, while THE levels decreased during the experiment, but rebounded substantially after the DX was withdrawn. Both DX and PL significantly interfered with the production of F and E, leading to their complete depletion. Taken together, the results demonstrate the influence of DX and PL administration on 11βHSD activity and their impact on dysfunction of the 5-reductase pathway. In conclusion, profiling tetrahydrometabolites of F and E might serve as an alternative, indirect but reliable, non-invasive procedure for assessing the impact of synthetic glucocorticosteroids administration. ARTICLE HISTORY

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Section: Methods Validationmentioning

confidence: 87%

Section: Methods Validationmentioning

confidence: 99%

Section: Methods Validationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

HPLC-ESI-MS/MS assessment of the tetrahydro-metabolites of cortisol and cortisone in bovine urine: promising markers of dexamethasone and prednisolone treatment

Chiesa

Panseri

Pavlović

et al. 2016

Food Additives & Contaminants: Part A

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Hormones and &;#x003B2;&;#x02010;Agonists

Ginkel

Bovee

Blokland

et al. 2016

Chemical Analysis of Non&;#x02010;antimicrobial Veterinary Drug Residues in Food

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Metabolic fingerprinting reveals a novel candidate biomarker for prednisolone treatment in cattle

et al. 2015

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The use of glucocorticoids as growth promoters for meat-producing animals is strictly regulated within the European Union. However, in the past few years, a higher frequency of non-compliant bovine urine samples for prednisolone has been noticed, which could not be directly related to fraudulent use of prednisolone. As such, questions have risen about the origin of this compound. Unfortunately, at present, no decisive strategy has been established to discriminate between endogenous and exogenous prednisolone. In this study, an untargeted metabolomics strategy, based on Orbitrap and QqTOF mass spectrometry, was deployed to reveal urinary biomarkers, which are indicative for the exogenous administration of the synthetic glucocorticoid prednisolone. For this purpose, prednisolone was administered intramuscularly and per os to 12 bovines and a total of 2700 urine samples were collected before, during and after treatment. Multivariate statistical data analysis (i.e. OPLS-DA) revealed four differentiating metabolites that allowed discrimination between urine samples collected before and during prednisolone administration. None of these compounds were present in urine containing endogenous prednisolone, of which the formation was induced by the administration of a synthetic analogue of adrenocorticotropic hormone. Only one metabolite was retained as a highly suitable biomarker during growth-promoting and therapeutic prednisolone treatment, with 93.4 % sensitivity and 96.3 % specificity. Besides, this compound could be detected up to 4 days after a single therapeutic per os prednisolone administration. Based on accurate mass, isotope pattern, and MS/MS spectra, this compound was putatively annotated and is suggested as an actionable biomarker for exogenous prednisolone administration

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Excretion profile of corticosteroids in bovine urine compared with tissue residues after therapeutic and growth-promoting administration of dexamethasone

Cited by 14 publications

References 15 publications

HPLC-ESI-MS/MS assessment of the tetrahydro-metabolites of cortisol and cortisone in bovine urine: promising markers of dexamethasone and prednisolone treatment

HPLC-ESI-MS/MS assessment of the tetrahydro-metabolites of cortisol and cortisone in bovine urine: promising markers of dexamethasone and prednisolone treatment

Hormones and &;#x003B2;&;#x02010;Agonists

Metabolic fingerprinting reveals a novel candidate biomarker for prednisolone treatment in cattle

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