Sub-therapeutic treatments of bulls with dexamethasone: direct and indirect markers of treatment

Abstract

Dexamethasone is a potent synthetic corticosteroid synthesised as an anti-inflammatory agent, but also illegally used at low dosages as a growth promoter either alone or in combination with other steroids or β-agonists. The use of screening methods based on the detection of biological effects of growth promoters is a promising approach to assist residue monitoring. The advantage of such an approach is that it offers the possibility to discover illicit treatments even when the drug residues are not easily detectable by common analytical methods. The aim of this study was to determine the urinary elimination and tissue distribution of dexamethasone and to investigate whether endogenous corticosteroid profiling of urine could be used to establish a predictive tool for identifying any misuse of growth promoters in bulls. Urinary corticosteroid concentrations were assayed in bulls (n = 8) treated with dexamethasone (0.75 mg/animal/day), bulls (n = 8) treated with a combination of dexamethasone (0.66 mg/animal/day) and clenbuterol (from 2 to 6 mg/animal/day) and untreated bulls (n = 8). The distribution and elimination of dexamethasone and the urinary concentration of cortisone, cortisol and 6β-hydroxycortisol were determined by using LC-MS/MS at different time points both during treatments and after appropriate withdrawal times. The urinary concentration of endogenous corticosteroids in bulls decreased significantly (p < 0.001) upon the administration of dexamethasone alone, whereas it remained unchanged until the last sampling point in animals treated with dexamethasone and clenbuterol (p < 0.001). Nonetheless, dexamethasone administration significantly reduced (p < 0.01) the urinary 6β-hydroxycortisol/cortisol ratio in both treatment groups. Therefore, this ratio could be regarded as a candidate for an indirect screening assay for detecting glucocorticoid abuse in bull fattening to pick out farms where similar treatments are potentially in use and to suggest targeted sampling on remaining animals.

Keywords:

• cortisol
• cortisone
• dexamethasone
• indirect markers
• liquid chromatography-tandem mass spectrometry
• 6β-hydroxycortisol

Acknowledgements

The authors thank the Italian Ministry of Health (Project RF-IZPLV-2006-364645), Regione Veneto, for financial support and Maria Cristina Bellesso for her excellent technical assistance.

Notes

The first two authors contributed equally to this work.

The first two authors contributed equally to this work.

Additional information

Notes on contributors

Giancarlo Biancotto

The first two authors contributed equally to this work.

Roberto Stella

The first two authors contributed equally to this work.