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      Taxol and Taurine Protect the Renal Tissue of Rats after Unilateral Ureteral Obstruction: A Stereological Survey

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          Abstract

          Purpose

          Blockage of the urinary tract induces changes in renal structure including tubular dilatation or atrophy, tubular cell death, inflammatory processes, and progressive interstitial fibrosis with the loss of renal parenchyma. The present study was conducted to survey the protective effects of Taxol and taurine on the renal structure after unilateral ureteral obstruction (UUO).

          Materials and Methods

          UUO was induced in three groups of rats (n=6) who then received distilled water, Taxol (0.3 mg/kg/d), or taurine (7.5 mg/kg/d). Stereological methods were used to gather quantitative as well as comparative data.

          Results

          Less than -8% of the volume of the glomeruli, proximal convoluted tubules (PCT), distal convoluted tubules (DCT), Henle's loop, and collecting ducts were preserved after UUO. After treatment of the UUO rats with Taxol, between -32% and 88% of the parameters mentioned above remained intact, and after treatment of the UUO rats with taurine, between -16% and 46% of the parameters remained intact (p<0.01). Compared with the untreated UUO animals, the volume of necrotic and fibrotic tissues decreased -53% and -63% in the UUO rats treated with Taxol and taurine, respectively (p<0.01). Less than -3% of the lengths of the renal tubules (PCT, DCT, Henle's loop, and collecting) were preserved in the UUO rats. After treatment with Taxol and taurine, -61% to 70% and -43% to 53% of the length of the renal tubules were preserved, respectively (p<0.01).

          Conclusions

          Taurine and Taxol are effective in preventing some structural renal damage in a direct ureteral obstruction model. Taxol was more effective in renal protection.

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          Most cited references20

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          Some new, simple and efficient stereological methods and their use in pathological research and diagnosis.

          Stereology is a set of simple and efficient methods for quantitation of three-dimensional microscopic structures which is specifically tuned to provide reliable data from sections. Within the last few years, a number of new methods has been developed which are of special interest to pathologists. Methods for estimating the volume, surface area and length of any structure are described in this review. The principles on which stereology is based and the necessary sampling procedures are described and illustrated with examples. The necessary equipment, the measurements, and the calculations are invariably simple and easy.
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            Low-dose paclitaxel ameliorates renal fibrosis in rat UUO model by inhibition of TGF-beta/Smad activity.

            Transforming growth factor-beta (TGF-beta) has a pivotal function in the progression of renal fibrosis in a wide variety of renal diseases. Smad proteins have been identified to have an important function in regulating the expression of extracellular matrix (ECM) proteins through TGF-beta signaling pathway. Aberrant TGF-beta/Smad signaling can be modulated by stabilization of microtubules with paclitaxel. In this study, we investigated if paclitaxel can attenuate tubulointerstitial fibrosis in a rat model of unilateral ureteral obstruction (UUO). Rats in groups of six were subjected to UUO and received low-dose intraperitoneal injection of paclitaxel (0.3 mg/kg) twice a week. They were killed at day 7 and 14 after UUO or Sham operation. TGF-beta signaling cascade and status of various ECM proteins were evaluated by RT-PCR, western blotting and immunohistochemical or immunofluorescence staining. The paclitaxel treatment markedly suppressed Smad2 and Smad3 phosphorylation. This was associated with attenuated expression of integrin-linked kinase, collagens I and III, fibronectin (FN) and alpha-smooth muscle actin, and a substantial decrease in renal fibrosis in animals that underwent UUO and received paclitaxel. These data indicate that the low-dose paclitaxel ameliorates renal tubulointerstitial fibrosis by modulating TGF-beta signaling, and thus, the paclitaxel may have some therapeutic value in humans.
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              Sulforaphane protects kidneys against ischemia-reperfusion injury through induction of the Nrf2-dependent phase 2 enzyme.

              Reactive oxygen species are important mediators that exert a toxic effect during ischemia-reperfusion injury of various organs. Sulforaphane, which is a naturally occurring isothiocyanate that is present in cruciferous vegetables such as broccoli, is known to be an indirect antioxidant that acts by inducing Nrf2-dependent phase 2 enzymes. Phase 2 enzymes such as heme oxygenase-1, NAD(P)H: quinone oxidoreductase 1, glutathione reductase, and glutathione peroxidase participate in adaptive and protective responses to oxidative stress and various inflammatory stimuli. Therefore, we evaluated the preactivation of Nrf2 by sulforaphane to determine if it could inhibit ischemia-reperfusion-induced kidney damage. Treatment of HK2 renal tubular epithelial cells with sulforaphane effectively protected cells against cytotoxicity induced by hypoxia-reoxygenation, and sulforaphane dramatically induced phase 2 enzymes by decreasing the Keap1 protein levels and increasing Nrf2 nuclear translocation. Additionally, a second set of experiments using a renal ischemia-reperfusion model produced results that were essentially the same as those observed when HK2 cells were used; namely, that sulforaphane induced Nrf2-dependent phase 2 enzymes and thereby improved ischemia-reperfusion-induced changes in the lipid hydroperoxides, glutathione, creatinine clearance, kidney weight, and histologic abnormalities. Collectively, these results suggest that sulforaphane can be used as an effective adjunct for the prevention of renal oxidative insults during ischemia-reperfusion injury.
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                Author and article information

                Journal
                Korean J Urol
                Korean J Urol
                KJU
                Korean Journal of Urology
                The Korean Urological Association
                2005-6737
                2005-6745
                May 2012
                18 May 2012
                : 53
                : 5
                : 360-367
                Affiliations
                Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
                Author notes
                Corresponding Author: Ali Noorafshan. Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Zand Ave., Shiraz 71348-45794, Iran. TEL: +98-711-2304372, FAX: +98-711-2304372, noora@ 123456sums.ac.ir
                Article
                10.4111/kju.2012.53.5.360
                3364477
                22670197
                ad4ffc55-9ecd-4676-8db0-4f646be3de69
                © The Korean Urological Association, 2012

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 December 2011
                : 02 March 2012
                Categories
                Original Article
                Investigative Urology

                Urology
                ureteral obstruction,stereology,taurine,kidney,taxol
                Urology
                ureteral obstruction, stereology, taurine, kidney, taxol

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