Tetracycline protects against dermonecrosis induced by Loxosceles spider venom.
Envenomation by spiders belonging to the Loxosceles genus (brown spider) often results in local dermonecrotic lesions. We have previously shown that Loxosceles sphingomyelinase D (SMase D), the venom component responsible for all the pathological effects, induced the expression of matrix metalloproteinases (MMPs) in rabbits and in human keratinocytic cells. We also showed that the SMase D-induced apoptosis and MMP expression of keratinocytes was inhibited by tetracyclines. We have further investigated the ability of tetracyclines to inhibit or prevent the dermonecrotic lesion induced by Loxosceles venom in vivo and in vitro models. Primary cultures of rabbit fibroblasts incubated with increasing concentrations of venom or SMase D showed a decrease in cell viability, which was prevented by tetracyclines. In vivo experiments showed that topical treatments with tetracycline of rabbits, inoculated with crude Loxosceles intermedia venom or recombinant SMase D, significantly reduced the progression of the dermonecrotic lesion. Furthermore, tetracyclines also reduced the expression of MMP-2 and prevented the induction of MMP-9. Our results suggest that tetracycline may be an effective therapeutic agent for the treatment of cutaneous loxoscelism.
Paixão-Cavalcante
Danielle
D
Laboratório de Imunoquímica, Instituto Butantan, São Paulo, Brazil.
van den Berg
Carmen W
CW
Gonçalves-de-Andrade
Rute M
RM
Fernandes-Pedrosa
Matheus de F
Mde F
Okamoto
Cinthya Kimori
CK
Tambourgi
Denise V
DV
D000818:Animals; D001733:Bites and Stings; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009336:Necrosis; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D010727:Phosphoric Diester Hydrolases / Q000633:toxicity*; D011817:Rabbits; D012871:Skin Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D013108:Sphingomyelin Phosphodiesterase / Q000633:toxicity; D013111:Spider Venoms / Q000633:toxicity*; D013112:Spiders; D013754:Tetracyclines / Q000494:pharmacology*
D013111:Spider Venoms; D013754:Tetracyclines; C055161:loxosceles venom; D010727:Phosphoric Diester Hydrolases; D013108:Sphingomyelin Phosphodiesterase; C495583:sphingomyelinase I, Loxosceles laeta; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9