title: Efficacy of poly(adenosine diphosphate-ribose) polymerase inhibition in extracorporeal shock wave-induced renal injury.
abstract: OBJECTIVE
  Extracorporeal shock wave lithotripsy (ESW) induces renal damage by excessive production of free oxygen radicals. Free Oxygen radicals cause cellular injury by inducing nicks in DNA. The enzyme poly(adenosine diphosphate-ribose) polymerase (PARP) involved in the process of repair of DNA in damaged cells. However, its activation in damaged cells can lead to adenosine triphosphate depletion and death. Thus, we designed a study to evaluate the efficacy of 3-aminobenzamide (3-AB), a PARP inhibitor, against extracorporeal shock wave induced renal injury.
  
  
  METHODS
  Twenty-four Sprague-Dawley rats were divided into three groups: control, ESW, ESW + 3-AB groups. All groups except control group were subjected to ESW procedure. ESW + 3-AB group received 20 mg/kg/day 3-aminobenzamide intraperitoneally at 2 h before ESW and continued once a day for consecutive 3 days. The surviving animals were sacrificed at the 4th day and their kidneys were harvested for biochemical and histopathologic analysis. Blood samples from animals were also obtained.
  
  
  RESULTS
  Serum ALT and AST levels, serum neopterin and tissue oxidative stress parameters were increased in the ESW group and almost came to control values in the treatment group (p < 0.05, ESW vs. ESW + 3-AB). Histopathological injury score were significantly lower in treatment group than the ESW group (p < 0.05, ESW vs. ESW + 3-AB).
  
  
  CONCLUSIONS
  Our data showed that PARP inhibition protected renal tissue against ESW induced renal injury. These findings suggest that it would be possible to improve the outcome of ESW induced renal injury by using PARP inhibitors as a preventive therapy.
authors.affiliation: Department of Urology, Gulhane Military Medical Academy Haydarpasa Training Hospital , Uskudar, Istanbul , Turkey .
authors.forename: Ercan
authors.initials: E
authors.lastname: Malkoc
authors.forename: Bilal Fırat
authors.initials: BF
authors.lastname: Alp
authors.forename: Zafer
authors.initials: Z
authors.lastname: Demirer
authors.forename: Ali
authors.initials: A
authors.lastname: Guragac
authors.forename: Furkan
authors.initials: F
authors.lastname: Dursun
authors.forename: Ferhat
authors.initials: F
authors.lastname: Ates
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yildirim
authors.forename: Ramazan
authors.initials: R
authors.lastname: Yuksel
authors.forename: Bulent
authors.initials: B
authors.lastname: Uysal
authors.forename: Turgut
authors.initials: T
authors.lastname: Topal
authors.forename: Yasemin Gulcan
authors.initials: YG
authors.lastname: Kurt
authors.forename: Ayhan
authors.initials: A
authors.lastname: Ozcan
authors.forename: Ahmet
authors.initials: A
authors.lastname: Guven
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008096:Lithotripsy / Q000009:adverse effects*; D008297:Male; D019798:Neopterin / Q000097:blood; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D019798:Neopterin; C025160:3-aminobenzamide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: 3-aminobenzamide; PARP inhibition; extracorporeal shock wave lithotripsy; oxidative stress; renal injury