Inhibition of inducible nitric oxide synthase prevents shock wave therapy induced renal injury

Abstract

Objectives: Shock wave lithotripsy treatment (SWT) is not completely free from side effects; one of the accused mechanisms for renal injury during SWT is oxygen-and nitrogen-derived free radical productions. Therefore, we aimed to evaluate the effect of inhibition of nitric oxide (NO) production by N-[3(aminomethyl) benzyl) acetamidine] (1400W), highly selective inducible nitric oxide synthase (iNOS) inhibitor, at SWT-induced kidney damage. Materials and methods: Twenty-four rats those underwent right nephrectomy procedure were divided equally into three groups as control, SWT, and SWT + 1400W. 1400W was administered at a dose of 10 mg/kg at 2 h prior to SWT procedure and at the beginning of SWT procedure via intraperitoneal route and continued daily for consecutive 3 days. At the end of the fourth day, animals were killed via decapitation and trunk blood and the left kidneys were taken for biochemical and histopathologic evaluation. Results: SWT caused renal tubular damage and increased lipid peroxidation and antioxidant enzyme activities and SWT also significantly increased nitro-oxidative products. Inhibition of iNOS via administration of 1400W ameliorated renal injury and decreased tissue lipid peroxidation (malondialdehyde), superoxide dismutase, glutathione peroxidase and nitrite/nitrate levels (NO x ). In addition, it was seen that histolopathological changes were attenuated in the SWT + 1400W group when compared to SWT group. Conclusion: SWT-induced renal injury might be due to excessive production of oxygen free radicals and NO production. Inhibition of iNOS attenuates renal injury following SWT treatment. It can be concluded that iNOS inhibitors or peroxynitrite scavengers might be used to protect the kidneys against SWT-induced morphological and functional injuries.

Efficacy of poly(adenosine diphosphate-ribose) polymerase inhibition in extracorporeal shock wave-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 previous study. 16 Therefore, we assume that creatinine is secreted more than normally from proximal tubules in rats ESW procedure resulting in lower serum creatinine level. Another explanation for this situation may be related to different protein channels for each reabsorbed molecules and this needs further studies.…”

“…Applied the number of shock waves and the level of energy were decided based on previous studies and our preliminary studies. [14][15][16][17] After ESW procedure, rats were returned to their cages.…”

Medical ozone therapy reduces shock wave therapy-induced renal injury

“…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).…”