Efficacy of poly(adenosine diphosphate-ribose) polymerase inhibition in extracorporeal shock wave-induced renal injury

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 (p50.05, ESW vs. ESW + 3-AB). Histopathological injury score were significantly lower in treatment group than the ESW group (p50.05, 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.

Medical ozone therapy reduces shock wave therapy-induced renal injury

“…Renal injury due to ESW is especially and intensively occurred in proximal tubulus as shown our histopathologic evaluation and our iNOS immunohistochemical staining in our previous studies. 8,9 Therefore, we assume that creatinine and electrolytes are secreted more than normally from proximal tubules in rats subjected to Table 3. Pathologic scores.…”

“…The number of shock waves applied and the level of energy were decided based on previous studies and our preliminary studies. 8,9,24,25 After ESW procedure, rats were returned to their cages.…”

“…3,4 Several clinical and experimental studies have reported that sound waves on the kidney cause damage to tissue in exposed kidney. 1,[5][6][7][8][9] Although the mechanism of renal injury after ESW is still not well-defined, more recently free oxygen radical production originating from transient ischemia due to ESW application has been considered to be an integral element in shock wave-induced renal damage. 7,10,11 Studies, measuring renal resistive index or followed renal blood velocity in the kidney subjected to SWT, showed that an increase in resistive index or a reduction in blood velocity indicative of vasoconstriction occurred.…”

“…It is assumed that this transient ischemia and following reperfusion causes release of cytokines/inflammatory cellular mediators, production of oxygen-derived free radicals and nitrogen-derived free radicals, and infiltration of tissue by inflammatory response cells, and this process initiates the cellular damage and death. 6,8,9,14 Moreover, many experimental studies have shown that renal injury following ESW can be prevented by antioxidant treatment modalities such as melatonin, coenzyme Q10, curcumin, and vitamin E; 5,6,14 the main purpose of these studies was to inhibit inflammatory reaction at the early phase so as to prevent renal damage. Our recent works also showed that SWT causes renal injury, especially at the proximal tubular system, and we demonstrated that this injury is due to excessive production of oxygen free radicals and nitric oxide (NO) production.…”

“…In addition, we demonstrated that iNOS inhibitors or peroxynitrite scavengers might protect the kidneys against SWT-induced morphological and functional injury. 8,9 Ozone (O 3 ), a gas composed of three oxygen atoms, is continuously produced in the stratosphere by UV radiation or during the electric discharge of lightning from atmospheric oxygen. A gas mixture comprising ozone/ oxygen used in medicine is known as medical ozone therapy (OT).…”