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Pyrrolidine dithiocarbamate attenuate shock wave induced MDCK cells injury via inhibiting nuclear factor-kappa B activation

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Abstract

Shock wave lithotripsy (SWL)-induced renal damage appears to be multifactorial. Recent data indicated that the mechanism of renal tissue damage secondary to SWL is similar to that of ischemia reperfusion injury. Nuclear factor-kappa B (NFκB) and its target genes, inducible nitric oxide synthase (iNOS) and cyclooxygense-2 (COX-2), have been demonstrated to play a very important role in a variety of cells or tissues ischemia reperfusion injuries. Thus in the present study, using an in vitro model MDCK cells, we investigated the role of NFκB and its target cytotoxic enzyme in shock wave-induced renal cellular damage. We also examined whether inhibition this pathway by pyrrolidine dithiocarbamate (PDTC) is contributed to alleviate SWL-caused cell damage. Suspensions of MDCK cells were placed in containers for shock wave exposure. Three groups of six containers each were examined: control group, no shock wave treatment and SWL group, which received 100 shocks at 18 kV; 3 SWL + PDTC group. PDTC were added to the suspensions before shock wave exposure. After shock wave 0, 2, 4, 6 and 8 h, respectively, the cell supernatants were detected for the level of MDA and release of LDH. At post-shock wave 8 h, cells were harvested to detect the nuclear translocation of NFκBp65 by immunofluorescence staining. Degradation of IκB-а (an inhibitor protein of NFκB) and expression of iNOS and COX-2 were also examined by western blotting. Our results indicated that shock wave initiated the apparent activation of NFκB, which in turn induced high expression of iNOS and COX-2. Blocking degradation of IκB-а by PDTC was contributed to decrease the expression of iNOS. And the level of MDA and the release of LDH were also significantly reduced by using PDTC. However, the degree of COX-2 expression does not differ significantly between SWL and SWL + PDTC groups. Activation of NFκB and subsequent expression of its target cytotoxic enzyme have been demonstrated to be a potential and crucial mechanism in SWL-induced renal cell damage. Blocking this pathway by PDTC is contributed to protect against cellular damage from shock wave.

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Authors and Affiliations

  1. Department of Urology, No. 1 Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi Province, 710061, China

    Xiang Li, Dalin He, Linlin Zhang, Yuquan Xue, Xinfa Cheng & Yong Luo

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  1. Xiang Li
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  2. Dalin He
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Correspondence to Dalin He.

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Li, X., He, D., Zhang, L. et al. Pyrrolidine dithiocarbamate attenuate shock wave induced MDCK cells injury via inhibiting nuclear factor-kappa B activation. Urol Res 35, 193–199 (2007). https://doi.org/10.1007/s00240-007-0105-5

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