Abraham G, Allersmeier M, Gottschalk J, Schusser G F, Hoppen H-O, Ungemach F R
Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
J Vet Pharmacol Ther. 2009 Aug;32(4):379-87. doi: 10.1111/j.1365-2885.2008.01054.x.
There are no data available regarding the systemic (adverse) effects which might be induced by topical/dermal glucocorticoids (GCs) application in the horse. Besides their widespread use for the treatment of a variety of peripheral inflammatory disorders such as atopic dermatitis, eczemas or arthritis in the horse, their surreptitious application has become a concern in doping cases in competition/performance horses. Assessing both basal and ACTH-stimulated plasma cortisol as well as basal ACTH concentrations following application of dexamethsone-containing dermal ointment is necessary to determine influences on hypothalamus-pituitary-adrenal (HPA) axis. Ten clinically healthy adult standardbred horses (6 mares, 4 geldings) were rubbed twice daily each with 50 g dexamethasone-containing ointment on a defined skin area (30 x 50 cm) for 10 days. RIA and chemiluminescent enzyme immuno-metric assay were used to determine resting and ACTH-stimulated plasma cortisol and basal ACTH concentrations, respectively. HPA feedback sensitivity and adrenal function were measured by a standard ACTH stimulation test. Dermal dexamethasone suppressed significantly the resting plasma cortisol level (to 75-98%) below baseline (P < 0.001) within the first 2 days and decreased further until day 10. ACTH stimulation test showed a markedly reduced rise in plasma cortisol concentrations (P < 0.001 vs. baseline). Plasma ACTH level decreased also during topical dexamethasone application. The number of total lymphocytes and eosinophil granulocytes was reduced, whereas the number of neutrophils increased. No significant change of serum biochemical parameters was noted. Dermal dexamethasone application has the potential to cause an almost complete and transient HPA axis suppression and altered leukocyte distribution in normal horses. The effects on HPA axis function should be considered in relation to the inability of animals to resist stress situations. The data further implicate that percutaneously absorbed dexamethasone (GCs) may cause systemic effects relevant to 'doping'.
关于局部/经皮应用糖皮质激素（GCs）可能对马匹产生的全身（不良）影响，目前尚无相关数据。除了广泛用于治疗马匹的各种外周炎症性疾病，如特应性皮炎、湿疹或关节炎外，其在比赛/表演马匹的兴奋剂检测案例中被偷偷使用也已成为一个问题。在应用含地塞米松的皮肤软膏后，评估基础和促肾上腺皮质激素（ACTH）刺激后的血浆皮质醇以及基础ACTH浓度，对于确定其对下丘脑-垂体-肾上腺（HPA）轴的影响是必要的。十匹临床健康的成年标准赛马（6匹母马，4匹阉马），每天在规定的皮肤区域（30×50厘米）涂抹含50克地塞米松的软膏两次，持续10天。分别采用放射免疫分析（RIA）和化学发光酶免疫分析方法测定静息和ACTH刺激后的血浆皮质醇以及基础ACTH浓度。通过标准的ACTH刺激试验测量HPA轴的反馈敏感性和肾上腺功能。皮肤应用地塞米松在最初2天内显著抑制静息血浆皮质醇水平（降至基线以下的75 - 98%，P < 0.001），并持续下降直至第10天。ACTH刺激试验显示血浆皮质醇浓度的升高明显降低（与基线相比，P < 0.001）。在局部应用地塞米松期间，血浆ACTH水平也降低。总淋巴细胞和嗜酸性粒细胞数量减少，而中性粒细胞数量增加。未观察到血清生化参数的显著变化。皮肤应用地塞米松有可能导致正常马匹的HPA轴几乎完全且短暂的抑制以及白细胞分布改变。考虑到动物无法抵抗应激情况，应对HPA轴功能的影响加以考虑。这些数据进一步表明，经皮吸收的地塞米松（GCs）可能会引起与“兴奋剂”相关的全身效应。
