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

Atopic dermatitis‐like symptoms in hypomagnesaemic hairless rats are prevented and inhibited by... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Dermatology Wiley

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

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Publisher
Wiley
Copyright
Copyright © 2000 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0007-0963
eISSN
1365-2133
DOI
10.1046/j.1365-2133.2000.03411.x
Publisher site
See Article on Publisher Site

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.

Journal

British Journal of DermatologyWiley

Published: Apr 1, 2000

References

  • The dermatosis of hairless rats fed a hypomagnesaemic diet. I. Course, clinical features and inhibition by drugs.
    Ponvert, Ponvert; Galoppin, Galoppin; Saurat, Saurat
  • Superoxide anion in polymorphonuclear leukocytes of hairless rats suffering from magnesium deficiency dermatitis.
    Hanada, Hanada; Hashimoto, Hashimoto
  • A novel anti‐inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology.
    Grassberger, Grassberger; Baumruker, Baumruker; Enz, Enz
  • A novel anti‐inflammatory drug, SDZ ASM 981, for the topical and oral treatment of skin diseases: in vivo pharmacology.
    Meingassner, Meingassner; Grassberger, Grassberger; Fahrngruber, Fahrngruber
  • Human mast cell cytokines.
    Bradding, Bradding
  • Mast cells, eosinophils and fibrosis.
    Levi‐Schaffer, Levi‐Schaffer; Weg, Weg
  • Enhanced NO production during Mg deficiency and its role in mediating red blood cell glutathione loss.
    Mak, Mak; Komarov, Komarov; Wagner, Wagner
  • Inhibitory effect of the leukotriene B 4 receptor antagonist against hypomagnesic diet‐induced dermatitis in hairless rats.
    Hanada, Hanada; Mitsuhashi, Mitsuhashi; Hashimoto, Hashimoto

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