title: Renoprotective Effects of DNAse-I Treatment in a Rat Model of Ischemia/Reperfusion-Induced Acute Kidney Injury.
abstract: Massive DNA destruction/accumulation of cell-free DNA debris is a sensitive biomarker of progressive organ/tissue damage. Deleterious consequences of DNA debris accumulation are evident in cardiac ischemia, thrombosis, auto-inflammatory diseases, SLE-induced lupus nephritis and cystic fibrosis. In case of renal pathologies, degradation and elimination of DNA debris are suppressed, due to downregulated DNAse-I activity within the diseased kidneys. The aim of the current study was to evaluate whether exogenous DNAse-I administration might exert renoprotective effects in the setting of acute kidney injury (AKI or acute renal failure).
  
  
  
  Sprague-Dawley rats underwent unilateral nephrectomy, with simultaneous clamping of contralateral kidney artery. The treated group received DNAse-I injection before discontinuing anesthesia. Positive (ischemic) controls received saline injection. Negative (non-ischemic) controls were either non-operated or subjected to surgery of similar duress and duration without ischemia. Renal perfusion was evaluated using the Laser-Doppler technique. Blood was procured for evaluating DNAse-I activity, renal functioning, renal perfusion. The kidneys were allocated for histopathologic examinations and for the evaluation of renal hypoxia, intra-renal apoptosis and proliferation.
  
  
  
  Contrary to the situation in untreated ischemic rats, renal perfusion was significantly improved in DNAse-treated animals, concomitantly with significant amelioration of damage to renal functioning and tissue integrity. Treatment with DNAse-I significantly decreased the ischemia-induced renal hypoxia and apoptosis, simultaneously stimulating renal cell proliferation. Exogenous DNAse-I administration accelerated the clearance of intra-renal apoptotic DNA debris.
  
  
  
  Functional/histologic hallmarks of renal injury were ameliorated, renal functioning improved, intra-renal hypoxia decreased and intra-renal regeneration processes were activated. Thus, DNAse-I treatment protected the kidney from deleterious consequences of ischemia-induced AKI.
authors.affiliation: Research and Development Unit, Assaf Harofeh Medical Center, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Zerifin, Israel.
authors.forename: Victoria
authors.initials: V
authors.lastname: Peer
authors.forename: Ramzia
authors.initials: R
authors.lastname: Abu Hamad
authors.forename: Sylvia
authors.initials: S
authors.lastname: Berman
authors.forename: Shai
authors.initials: S
authors.lastname: Efrati
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D049109:Cell Proliferation / Q000187:drug effects; D003850:Deoxyribonuclease I / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D008297:Male; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D015427:Reperfusion Injury / Q000097:blood / Q000517:prevention & control*
chemical_list: D015415:Biomarkers; D003850:Deoxyribonuclease I