Effects of low-dose dexamethasone and prednisolone long term administration in beef calf: Chemical and morphological investigation

An analytical, pharmacokinetic and histopathologic investigation was conducted by two experimental trials on beef cattle in order to determine fate and effects of dexamethasone and prednisolone, administered to distinct cattle groups at low dosage for long periods of time. In trial 1, eighteen Charolaise beef cattle, male, 17-22-months-old, were divided in three groups: to group A (n = 6) dexamethasone-21-sodium-phosphate 0.7 mg day(-1) per os for 40 days was administered: group B (n = 6) was orally treated with prednisolone 15 mg day(-1) for 30 days, while group C (n = 6) served as negative control. Urine was collected at days 0, 7, 15,25 and 47 from groups A and C. and at days 0, 8, 18 and 42 from group B. In trial 2, sixteen Friesian cattle, male, 10-17-months-old, were randomly divided into two groups: group D (n = 8) was administered prednisolone 30 mg day(-1) per as for 35 days, while group K (n = 8) served as control. In both trials, the animals were slaughtered after a 6-days drug withdrawal and thymus and livers were collected and properly stored until the analysis was performed. Quantitative determinations of dexamethasone, prednisolone and its main metabolite. prednisone, in urine and liver samples were conducted by HPLC-MS/MS, after the analytical procedure was optimized and fully validated. The method validation included the assessment of specificity, linearity, precision, trueness, robustness, CC(alpha) and CC(beta) values. By a morphological point of view, severe atrophy of thymus parenchyma was observed in group A, together with a significant (P<0.005) reduction of the mean thymus weight (217 +/- 94 g), while group B (646 +/- 215 g) presented normal thymus features and weights (group C, 415 +/- 116 g). Accordingly, no differences were found in trial 2 for groups D (727 +/- 275 g) and K (642 +/- 173 g). Average dexamethasone concentrations in group A urine samples ranged from 1.4 to 3.0 mu g L(-1) during the treatment, while no residue was detected in the urine samples collected 6-7 days after the end of the treatment. Low amounts of dexamethasone (<1 mu g L(-1)) were detected in liver samples of group A. All average prednisolone concentrations in group B urine samples (sum of conjugate and free form) turned out to be below 1.0 mu g L(-1) during the treatment, despite the much higher concentration administered (15-30 mg day(-1)) with respect to dexamethasone in group A (0.7 mg day(-1)). No prednisolone residues were found in the urine and liver samples taken at the slaughterhouse. The absence of any prednisolone residue in the urine samples of control group animals supports the theory that the origin of this molecule is fundamentally exogenous, at least for this cattle category maintained under unstressing conditions. Remarkable findings are represented by the absence of thymus atrophy in the prednisolone treated animals and the extremely low residue concentrations found in urine during the treatment. Both findings reveal that the detection of illegal growth-promoting treatments with this drug is difficult. (C) 2010 Elsevier B.V. All rights reserved.