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The effect of renal administration of a selective cyclooxygenase-2 inhibitor or stable prostaglandin I2 analog on the progression of sclerotic glomerulonephritis in rats

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Abstract

Background and methods

There is increasing evidence that a change in glomerular hemodynamics may promote the development of glomerulosclerosis. In this study, we focused on the pharmacological effects of 2 contrasting agents, etodolac, a preferential cyclooxygenase-2 inhibitor, and beraprost sodium (BPS), a prostaglandin I2 analog, delivered renally, on the disease course of progressive anti-Thy-1 (ATS) glomerulonephritis.

Results

Intravital microscopic analysis showed that the diameters of glomerular capillaries and glomerular blood flow in unilaterally nephrectomized (Nx) rats treated locally with BPS were significantly increased, as compared to those of Nx rats treated locally with normal saline (NS) or etodolac. We then examined the effects of BPS and etodolac on the course of progressive glomerulosclerosis. Mesangial cell proliferation, adhesion of glomerular capillary tufts and crescent formation in the BPS-treated group appeared to be more severe compared to the ATS + NS and the ATS + etodolac groups. Scoring of mesangial proliferation and glomerulosclerosis revealed that local BPS treatment significantly worsened glomerular pathology. At day 28, there were significant differences in blood flow between the ATS + etodolac group and both the ATS + NS and ATS + BPS groups, indicating that local treatment with etodolac enhanced the recovery of glomerular circulation.

Conclusion

This study provides hemodynamic-based evidence showing that disturbance of intraglomerular microcirculation is a critical marker for progressive glomerulonephritis.

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Acknowledgments

This study was supported by research grants from the Ministry of Education, Science, Sports and Culture, Japan (B: No. 15390266, C: No. 12671032, JSPS; 15/03138, to T.O. Grant-in-aid for young scientists B: No. 17790548 to J.M.), and grants from Novartis Pharmaceuticals and Nippon Shinyaku Co., Ltd.

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Authors and Affiliations

  1. Department of Cellular Physiology, Institute of Nephrology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan

    Yukiko Nozawa, Ayako Sato, Hoglan Piao, Tetsuo Morioka & Takashi Oite

  2. Department of Internal Medicine II, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan

    Yukiko Nozawa & Ichiei Narita

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  1. Yukiko Nozawa
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  2. Ayako Sato
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  3. Hoglan Piao
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  4. Tetsuo Morioka
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  5. Ichiei Narita
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  6. Takashi Oite
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Corresponding author

Correspondence to Takashi Oite.

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Nozawa, Y., Sato, A., Piao, H. et al. The effect of renal administration of a selective cyclooxygenase-2 inhibitor or stable prostaglandin I2 analog on the progression of sclerotic glomerulonephritis in rats. Clin Exp Nephrol 16, 221–230 (2012). https://doi.org/10.1007/s10157-011-0558-2

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  • DOI: https://doi.org/10.1007/s10157-011-0558-2

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