title: Histological and functional renal alterations caused by Bothrops alternatus snake venom: expression and activity of Na+/K+-ATPase.
abstract: BACKGROUND
  Acute renal failure is a serious complication of human envenoming by Bothrops snakes. The ion pump Na+/K+-ATPase has an important role in renal tubule function, where it modulates sodium reabsorption and homeostasis of the extracellular compartment. Here, we investigated the morphological and functional renal alterations and changes in Na+/K+-ATPase expression and activity in rats injected with Bothrops alternatus snake venom.
  
  
  METHODS
  Male Wistar rats were injected with venom (0.8 mg/kg, i.v.) and renal function was assessed 6, 24, 48 and 72 h and 7 days post-venom. The rats were then killed and renal Na+/K+-ATPase activity was assayed based on phosphate release from ATP; gene and protein expressions were assessed by real time PCR and immunofluorescence microscopy, respectively.
  
  
  RESULTS
  Venom caused lobulation of the capillary tufts, dilation of Bowman's capsular space, F-actin disruption in Bowman's capsule and renal tubule brush border, and deposition of collagen around glomeruli and proximal tubules that persisted seven days after envenoming. Enhanced sodium and potassium excretion, reduced proximal sodium reabsorption, and proteinuria were observed 6 h post-venom, followed by a transient decrease in the glomerular filtration rate. Gene and protein expressions of the Na+/K+-ATPase α1 subunit were increased 6h post-venom, whereas Na+/K+-ATPase activity increased 6 h and 24 h post-venom.
  
  
  CONCLUSIONS
  Bothrops alternatus venom caused marked morphological and functional renal alterations with enhanced Na+/K+-ATPase expression and activity in the early phase of renal damage.
  
  
  CONCLUSIONS
  Enhanced Na+/K+-ATPase activity in the early hours after envenoming may attenuate the renal dysfunction associated with venom-induced damage.
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), CP 6111, 13083-970, Campinas, SP, Brazil.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Linardi
authors.forename: Thomaz A A
authors.initials: TA
authors.lastname: Rocha e Silva
authors.forename: Elen H
authors.initials: EH
authors.lastname: Miyabara
authors.forename: Carla F
authors.initials: CF
authors.lastname: Franco-Penteado
authors.forename: Kiara C
authors.initials: KC
authors.lastname: Cardoso
authors.forename: Patrícia A
authors.initials: PA
authors.lastname: Boer
authors.forename: Anselmo S
authors.initials: AS
authors.lastname: Moriscot
authors.forename: José A R
authors.initials: JA
authors.lastname: Gontijo
authors.forename: Paulo P
authors.initials: PP
authors.lastname: Joazeiro
authors.forename: Carla B
authors.initials: CB
authors.lastname: Collares-Buzato
authors.forename: Stephen
authors.initials: S
authors.lastname: Hyslop
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced; D000818:Animals; D017837:Bothrops; D003435:Crotalid Venoms / Q000633:toxicity*; D015870:Gene Expression; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*
chemical_list: D003435:Crotalid Venoms; D000254:Sodium-Potassium-Exchanging ATPase