Effects of dermal dexamethasone application on ACTH and both basal and ACTH-stimulated cortisol concentration in normal horses.
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'.
Abraham
G
G
Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany. gabraham@rz.uni-leipzig.de
Allersmeier
M
M
Gottschalk
J
J
Schusser
G F
GF
Hoppen
H-O
HO
Ungemach
F R
FR
D000279:Administration, Cutaneous; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000097:blood; D001774:Blood Chemical Analysis / Q000662:veterinary; D003907:Dexamethasone / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006403:Hematologic Tests / Q000662:veterinary; D006736:Horses / Q000097:blood*; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay / Q000662:veterinary; D016037:Single-Blind Method
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone