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Action mechanisms of the sphingomyelinases D from Loxosceles intermedia spider venom involved in cutaneous loxoscelism

Author(s):
Paixão-Cavalcante, Danielle
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo. [2005]. 184 f.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas
Defense date:
Examining board members:
Tambourgi, Denise Vilarinho; Chudizinski-Tavassi, Ana Marisa; Campa, Ana; Issac, Loudes; Teixeira, Catarina de Fátima Pereira
Advisor: Tambourgi, Denise Vilarinho
Field of knowledge: Biological Sciences - Immunology
Indexed in: Banco de Dados Bibliográficos da USP-DEDALUS
Location: Universidade de São Paulo. Biblioteca do Instituto de Ciências Biomédicas; ICB/T-ICB BMI QW504; P149m 2005
Abstract

Sphingomyelinases D (SMase D) from venom of spiders that belong to Loxosceles genus are considered the main responsible for induction of systemic and cutaneous effects observed after envenomation. The majority of the victims, approximately 90%, shows in the bite site an ulcer of difficult healing. The lack of a specific therapy to restrain the lesion development has carried us to study the action mechanisms after envenomation. The results obtained showed that the SMase D activates endogenous metalloproteinases, such as MMP 2 and MMP 9, in the site of the bite, which are positively associated to cell viability reduction, morphological alterations, decrease of cell surface markers and apoptosis induction in keratinocytes and fibroblasts "in vitro" and by dermonecrotic lesion development "in vivo". The damage induced by SMase D, "in vitro", was controlled by the use of metalloproteinases inhibitors, such as tetracyclines, which were also responsible for the reduction, around 50%, of the dermonecrotic lesion development "in vivo". Our results indicate that the endogenous metalloproteinases inhibition can control the cutaneous loxoscelism development and that tetracyclines may be used as safe and efficient therapy. (AU)