Atopic dermatitis-like symptoms in hypomagnesaemic hairless rats are prevented and inhibited by systemic or topical SDZ ASM 981

Abstract

Magnesium deficiency in hairless rats results in a transient erythematous rash within several days, the pathogenetic mechanisms of which are not yet well defined. However, the extremely pruritic rash closely mimics the acute clinical features of atopic dermatitis. Owing to the similarity of clinical signs between hypomagnesaemic rats and patients with atopic dermatitis, this rodent skin condition holds promise as a model for the in vivo evaluation of new treatment modalities against pruritic inflammatory skin conditions. The efficacy of the new ascomycin macrolactam derivative SDZ ASM 981 was tested in hypomagnesaemic rats by systemic or topical administration using prophylactic or therapeutic treatment regimens. Oral treatment of diseased rats with SDZ ASM 981 (12.5 mg kg-1 daily) inhibited the erythematous pruritic rash within 1 day after the start of treatment. This was associated with a clear reduction in histaminaemia, leucocytosis, eosinophilia and serum nitric oxide levels. The same daily oral dose of SDZ ASM 981 administered before the onset of the rash proved to be an efficacious prophylactic treatment regimen to prevent signs. Topical treatment of the ears with 0.4% SDZ ASM 981 locally inhibited and prevented inflammatory changes in a therapeutic and prophylactic treatment regimen, respectively. The histo- and immunopathological skin changes, as well as the numbers of degranulated mast cells in the dermis, were reversed towards normal after oral and topical administration. The pharmacological activity of SDZ ASM 981 reported here corresponds well to its anti-inflammatory and antipruritic activity observed in atopic dermatitis patients, confirming the usefulness of this rat model in drug evaluations.

Sargassum hemiphyllum Inhibits Atopic Allergic Reaction via the Regulation of Inflammatory Mediators

“…The important role of mast cells in immediate-type allergic reactions is well recognized. Several papers have described the involvement of mast cells in the skin rash in AD (29,30).…”

Antipruritische Wirkung von Pimecrolimus und Tacrolimus

“…Darüber hinaus konnte die juckreizlindernde Wirkung anhand eines Tiermodells verifiziert werden. Bei Ratten mit Symptomen einer akuter AD einschließlich eines starken Juckreizes konnte Pimecrolimus den Pruritus innerhalb der ersten Tage deutlich reduzieren [18].…”

Discovery of Topical Calcineurin Inhibitors and Pharmacological Profile of Pimecrolimus

“…Pimecrolimus is also topically active in murine irritant contact dermatitis models [72]. Furthermore, topical and oral pimecrolimus effectively reduces skin inflammation and pruritus and normalizes histopathological changes in hypomagnesemic hairless rats suffering from a disease that mimics the acute aspects of AD [73]. …”