Malkoc E et al, 2014: Efficacy of poly(adenosine diphosphate-ribose) polymerase inhibition in extracorporeal shock wave-induced renal injury.
Malkoc E, Alp BF, Demirer Z, Guragac A, Dursun F, Ates F, Yildirim I, Yuksel R, Uysal B, Topal T, Kurt YG, Ozcan A, Guven A
Department of Urology, Gulhane Military Medical Academy Haydarpasa Training Hospital , Uskudar, Istanbul , Turkey
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 < 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). 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.
Ren Fail. 2014 Sep 19:1-6. [Epub ahead of print]
Comments 1
Although various forms of tissue damage have been observed and described in experimental as well as clinical studies, it is noteworthy that the long-term clinical consequences of such tissue effects are either essentially absent or marginal. The authors mention in the Introduction hematuria as a sign of kidney damage. In my own experience in most cases this effect reflects a tearing of the mucosa by sharp fragments. Hematuria is observed in all patients when SWL results in stone disintegration and the long-term effect of this tearing is most certainly without significance. Occasionally (in SWL, in a simplified way described as follows:
Lipid peroxidation and levels of antioxidant enzymes were positively affected by 3-amino-benzamide. The results are of theoretical interest, but it is difficult to know if such a treatment might be of clinical relevance. Possibly patients exposed to repeat sessions of SWL might benefit from a similar regimen. Further studies need to be carried out in order to confirm this hypothesis.