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Alp BF et al, 2014: Inhibition of inducible nitric oxide synthase prevents shock wave therapy induced renal injury

Alp BF, Malkoc E, Demirer Z, Guragac A, Turker T, Altayli E, Ozcan A, Uysal B, Topal T, Akgul EO, Yildirim I, Guven A
Department of Urology, Gulhane Military Medical Faculty, Etlik, Ankara, Turkey


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 (NOx). In addition, it was seen that histolopathological changes were attenuated in the SWT + 1400W group when compared to SWT group.

CONCLUSIONS: 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.

Ren Fail. 2014 Feb 10. [Epub ahead of print]
PMID:24512212[PubMed - as supplied by publisher]

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Comments 1

Peter Alken on Tuesday, 18 February 2014 14:09

The rat kidney is a monopapillary kidney with a size of apr. 20x10x10 mm. This and the fact that the organ is not much bigger than the focal size makes the situation of the rat model not comparable to the human situation. In addition rat models do not seem to be standardized: Comparing two publications in this I 2014 review section, the current (1) and the one by Li X et al. (Li X Long Q, Cheng X, He D. Shock Wave Induces Biological Renal Damage by Activating Excessive Inflammatory Responses in Rat Model. Inflammation. 2014 (2) the reader will find big differences in the methods:

Current article:"...right kidney was removed, and clips were placed in the left renal fascia as the X-ray markers. After nephrectomy, in order to obtain a metabolic equilibration, rats were kept in their cages for 10 days. ...shock wave lithotripsy at the left kidney under the guidance of X-rays. Each rat received 2000 shocks, 18 kV, and total 15 J energy delivered with a Siemens Lithoskop[1] (Munich, Germany). The focal size is 16 mm, the pressure range is not known according to technical brochure and the focal depth is 16 cm. The shock wave rate was 60 shock waves/min. The shock waves were applied with ramping similar to human application. Applied the number of shock waves and the level of energy were decided based on previous studies and our preliminary studies.

Article by Li X et al.: "Rats were then cut the right kidney under general anesthesia ... and silver clips served as the X-ray markers were placed in the left renal fascia. ... All of the procedures were performed with a HK MZ-V lithotripter (Huikang, China). Each rat was received 500 shocks at the voltage of 18 kV."

It seems to me that the rat models can show nothing more but the SWL effects of a special model on rat kidneys.

Peter Alken

The rat kidney is a monopapillary kidney with a size of apr. 20x10x10 mm. This and the fact that the organ is not much bigger than the focal size makes the situation of the rat model not comparable to the human situation. In addition rat models do not seem to be standardized: Comparing two publications in this I 2014 review section, the current (1) and the one by Li X et al. (Li X Long Q, Cheng X, He D. Shock Wave Induces Biological Renal Damage by Activating Excessive Inflammatory Responses in Rat Model. Inflammation. 2014 (2) the reader will find big differences in the methods: Current article:"...right kidney was removed, and clips were placed in the left renal fascia as the X-ray markers. After nephrectomy, in order to obtain a metabolic equilibration, rats were kept in their cages for 10 days. ...shock wave lithotripsy at the left kidney under the guidance of X-rays. Each rat received 2000 shocks, 18 kV, and total 15 J energy delivered with a Siemens Lithoskop[1] (Munich, Germany). The focal size is 16 mm, the pressure range is not known according to technical brochure and the focal depth is 16 cm. The shock wave rate was 60 shock waves/min. The shock waves were applied with ramping similar to human application. Applied the number of shock waves and the level of energy were decided based on previous studies and our preliminary studies. Article by Li X et al.: "Rats were then cut the right kidney under general anesthesia ... and silver clips served as the X-ray markers were placed in the left renal fascia. ... All of the procedures were performed with a HK MZ-V lithotripter (Huikang, China). Each rat was received 500 shocks at the voltage of 18 kV." It seems to me that the rat models can show nothing more but the SWL effects of a special model on rat kidneys. Peter Alken
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