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Efficacy of poly(adenosine diphosphate-ribose) polymerase inhibition in extracorporeal shock wave-induced renal injury
Authors:Ercan Malkoc  Bilal Fırat Alp  Zafer Demirer  Ali Guragac  Furkan Dursun  Ferhat Ates
Affiliation:1. Department of Urology, Gulhane Military Medical Academy Haydarpasa Training HospitalUskudar, IstanbulTurkey;2. Department of Urology, Gulhane Military Medical AcademyEtlik, AnkaraTurkey;3. Department of Urology, Eskisehir Military HospitalEskisehirTurkey
Abstract:Objectives: 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?p?Conclusion: 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.
Keywords:3-aminobenzamide  extracorporeal shock wave lithotripsy  oxidative stress  PARP inhibition  renal injury
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