Profile of the urinary excretion of prednisolone and its metabolites in finishing bulls and cows treated with a therapeutic schedule

Abstract

BackgroundPrednisolone was one of the first glucocorticoids to be synthesised, but it is still widely applied to cattle. Illegal uses of prednisolone include its uses for masking a number of diseases before animal sale and, at lower dosages for extended periods of time, for the improvement of feed efficiency and carcass characteristics. Since occasional presence of prednisolone has been detected at trace level in urine samples from untreated cattle, the Italian Ministry of Health introduced a provisional limit of 5 ng/mL to avoid false non-compliances. However, this limit proved ineffective in disclosing prednisolone misuse as a growth-promoter. In the present study, prednisolone acetate was administered to finishing bulls and cows according to a therapeutic protocol (2 × 0.4-0.5 mg/kg bw i.m. at 48 h interval) to further verify the practical impact of this cut-off limit and develop sound strategies to distinguish between exogenous administration and endogenous production. Urinary prednisolone, prednisone, 20β-dihydroprednisolone, 20α-dihydroprednisolone, 20β-dihydroprednisone, 6β-hydroxyprednisolone, cortisol, and cortisone were determined using a validated LC/MS-MS method.ResultsThe urinary excretion profile showed the simultaneous presence of prednisolone, 20β-dihydroprednisolone, and prednisone, the latter at lower concentrations, up to 33 days after the first dosing. Higher analyte levels were detected in bulls even after correction for dilution in the urine. Prednisolone concentrations below 5 ng/ml were determined in half of the samples collected at 19 days, and in all the samples obtained 26 and 33 days after the first administration. No measurable concentrations of prednisolone or its metabolites were found in the samples collected before the treatment, while cortisol and cortisone levels lower than the respective LOQs were observed upon treatment.ConclusionsThe present study confirms the criticism of the coarse quantitative approach currently adopted to ascertain illegal prednisolone administration in cattle. As previously shown for growth-promoting treatments of meat cattle, the simultaneous determination of urinary prednisolone, prednisone, 20β-dihydroprednisolone, along with cortisol and cortisone, may represent a more reliable approach to confirm the exogenous origin of prednisolone. Such a strategy would facilitate unequivocal detection of animals treated with prednisolone acetate using a therapeutical protocol, even 3 to 4 weeks after the treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-014-0237-0) contains supplementary material, which is available to authorized users.

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

“…Nebbia et al (2014) also observed a decrease in F and E levels in finishing bulls and cows after therapeutic treatment with PL acetate. This is to some extent in contrast with our preliminary study (Pavlovic et al 2013) where no differences were found in the F and E excretion time course during PL treatment in male cattle.…”

“…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.…”

“…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.…”

Homologous ELISA for detection of prednisolone in human serum

“…Similarly PSL improves pulmonary function in horse and is being used in equine sports to increase athlete horse performance (Fidani et al, 2012). PSL is also being used illegally as a growth promoter in veal calves, bulls and old cows (Nebbia et al, 2014).…”

Pharmacokinetic and urinary profiling reveals the prednisolone/cortisol ratio as a valid biomarker for prednisolone administration

“…For example, the latter is frequently used in cattle, including dairy cows, for the treatment of allergic dermatitis, otitis, pruritus and musculoskeletal inflammation [ 1 , 2 ]. Apart from the therapeutic applications, synthetic glucocorticoids may also be administered unauthorized to promote the growth of veal calves, finishing bulls and cows at the end of their production cycle [ 3 ]. Glucocorticoids tend to increase live weight gain, improve feed intake, reduce the feed conversion ratio, reduce nitrogen retention, increase the fat content and promote water retention [ 4 ].…”