title: Tetracycline Reduces Kidney Damage Induced by Loxosceles Spider Venom.
abstract: Envenomation byLoxoscelesspider 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 inLoxoscelesspider venom responsible for local and systemic manifestations. This study aimed to investigate the toxicity ofL. intermediavenom 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,Loxoscelesvenom-induced kidney failure was observed, which was abrogated by administration of tetracycline. These results indicate that MMPs may play an important role inLoxoscelesvenom-induced kidney injury and that tetracycline administration may be useful in the treatment of human systemic loxoscelism.
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, São Paulo 05503-900, Brazil. cinthya.okamoto@butantan.gov.br.
authors.forename: Cinthya Kimori
authors.initials: CK
authors.lastname: Okamoto
authors.affiliation: Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff CF144XN, UK. vandenbergcw@cardiff.ac.uk.
authors.forename: Carmen W
authors.initials: CW
authors.lastname: van den Berg
authors.affiliation: Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. mmizu@med.nagoya-u.ac.jp.
authors.forename: Mizuno
authors.initials: M
authors.lastname: Masashi
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, São Paulo 05503-900, Brazil. rutemga2@gmail.com.
authors.forename: Rute M
authors.initials: RM
authors.lastname: Gonçalves-de-Andrade
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, São Paulo 05503-900, Brazil. denise.tambourgi@butantan.gov.br.
authors.forename: Denise V
authors.initials: DV
authors.lastname: Tambourgi
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D010727:Phosphoric Diester Hydrolases / Q000633:toxicity*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011507:Proteinuria / Q000139:chemically induced; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D013111:Spider Venoms / Q000633:toxicity*; D013112:Spiders; D013752:Tetracycline / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D020011:Protective Agents; D013111:Spider Venoms; C055161:loxosceles venom; D010727:Phosphoric Diester Hydrolases; C055160:sphingomyelin phosphodiesterase D; D053148:Caspase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D013752:Tetracycline
keywords: Loxosceles venom; kidney cells; kidney injury; matrix metalloproteinases (MMPs); sphingomyelinase D; tetracycline