Envenomation by Loxosceles spider can result in two clinical manifestations: cutaneous and systemic
loxoscelism, the latter of which includes
renal failure. Although incidence of
renal failure is low, it is the main cause of death, occurring mainly in children. The
sphingomyelinase D (SMase D) is the main component in
Loxosceles spider venom responsible for local and systemic manifestations. This study aimed to investigate the toxicity of L. intermedia
venom and SMase D on kidney cells, using both In vitro and in vivo models, and the possible involvement of endogenous
metalloproteinases (
MMP). Results demonstrated that
venom and SMase D are able to cause death of human kidney cells by apoptosis, concomitant with activation and secretion of extracellular matrix
metalloproteases, MMP-2 and MMP-9. Furthermore, cell death and
MMP synthesis and secretion can be prevented by
tetracycline. In a mouse model of systemic
loxoscelism,
Loxosceles venom-induced
kidney failure was observed, which was abrogated by administration of
tetracycline. These results indicate that
MMPs may play an important role in
Loxosceles venom-induced kidney injury and that
tetracycline administration may be useful in the treatment of human systemic
loxoscelism.