Loxosceles gaucho Venom-Induced Acute Kidney Injury – In Vivo and In Vitro Studies

Rui V Lucato,Isac Castro,Katia C Barbaro,Emmanuel A Burdmann,Maria A S F Baptista,Glória E Mendes,Patrícia M Cury,Regina C R M Abdulkader,Nestor Schor,Denise M C Malheiros,Luis Yu,David G Lalloo

doi:10.1371/journal.pntd.0001182

Abstract

BackgroundAccidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI). There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo.Methodology/Principal FindingsIn order to test Loxosceles gaucho venom (LV) nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control). LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats.Conclusions/Significance Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite.

Highlights

Loxosceles spiders can be found worldwide in temperate and tropical regions but their distribution is heavily concentrated in the Western Hemisphere [1,2]
In Brazil Loxosceles spiders were responsible for approximately 7,000 cases of spider envenomation per year
Even patients with mild cutaneous lesion may develop severe hemolysis and acute kidney injury (AKI), which is the main cause of death after these accidents

Summary

Introduction

Loxosceles spiders can be found worldwide in temperate and tropical regions but their distribution is heavily concentrated in the Western Hemisphere [1,2]. Loxosceles venom is a complex mixture of several proteins including alkaline phosphatase, hyaluronidase, 5-ribonucleotidase phosphohydrolase, sphingomyelinase D, several proteases, esterase and ATPase. Sphingomyelinase D is considered the most toxic fraction of the venom, playing a key role in its local and systemic action [1,2,3,4]. It causes neutrophil migration, complement system activation, cytokine and chemokine release and platelet aggregation [5]. Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI). There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo

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