Tetracycline Reduces Kidney Damage Induced by Loxosceles Spider Venom

• Published in: Toxins Vol. 9; no. 3; p. 90
• Main Authors: Okamoto, Cinthya Kimori, van den Berg, Carmen W, Masashi, Mizuno, Gonçalves-de-Andrade, Rute M, Tambourgi, Denise V
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.03.2017; MDPI
• Subjects: Animal models; Animals; Antibiotics; Apoptosis; Biocompatibility; Caspase 3 - metabolism; Cell death; Cell Line; Cell Survival - drug effects; Children; Damage; Extracellular matrix; Gelatinase A; Gelatinase B; Gene Expression - drug effects; Humans; In vitro methods and tests; Incidence; Kidney - drug effects; Kidney - pathology; kidney cells; kidney injury; Loxosceles venom; Male; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; matrix metalloproteinases (MMPs); Mice, Inbred BALB C; Mortality; Phosphoric Diester Hydrolases - toxicity; Protective Agents - pharmacology; Protective Agents - therapeutic use; Proteinuria - chemically induced; Renal failure; Renal Insufficiency - chemically induced; Renal Insufficiency - drug therapy; Renal Insufficiency - pathology; Rodents; Secretion; Sphingomyelin phosphodiesterase; sphingomyelinase D; Spider Venoms - toxicity; Spiders; tetracycline; Tetracycline - pharmacology; Tetracycline - therapeutic use; Toxicity; Venom; matrix metalloproteinases (MMPs); tetracycline; kidney injury; sphingomyelinase D; Loxosceles venom; kidney cells
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins9030090

Envenomation by 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 spider venom responsible for local and systemic manifestations. This study aimed to investigate the toxicity of 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, venom-induced kidney failure was observed, which was abrogated by administration of tetracycline. These results indicate that MMPs may play an important role in venom-induced kidney injury and that tetracycline administration may be useful in the treatment of human systemic loxoscelism.