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Sildenafil activates antioxidant and antiapoptotic genes and inhibits proinflammatory cytokine genes in a rat model of renal ischemia/reperfusion injury

  • Nephrology - Original article
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Abstract

Objectives

To study the possible renoprotective effect of sildenafil against renal ischemia/reperfusion (I/R) injury and its effect on the expression of some antioxidant, antiapoptotic gene and proinflammatory cytokine genes in rat model of renal I/R injury.

Materials and methods

One hundred and twenty male Sprague Dawley rats were subdivided into three equal groups: sham (underwent right nephrectomy without ischemia), control (underwent right nephrectomy and left ischemia for 45 min) and study [as control with 1 mg/kg sildenafil (per oral) 60 min before anesthesia]. Serum creatinine and BUN were measured at the baseline and the study endpoints (2, 24, 48 h and 7 days), and the left kidney was harvested at study endpoints for histopathological examination as well as for assessment of the expression of antioxidant genes (Nrf-2, HO-1 and NQO-1), antiapoptotic gene (Bcl-2) and inflammatory cytokines, e.g., TNF-a, IL-1β and ICAM-1.

Results

I/R caused significant increase in serum creatinine, BUN, histopathological damage score (p < 0.001) and significant reduction in antioxidant genes (nrf2, HO-1 and NQO-1) and antiapoptotic gene (Bcl2) with significant increase in TNF-a, IL-1β and ICAM-1 genes in kidney tissues. Pretreatment with sildenafil caused significant attenuation of serum creatinine and BUN as well as significant increase in the expression of antioxidant genes and Bcl-2 genes with significant reduction in the expression of proinflammatory cytokine genes (p value < 0.001).

Conclusion

The renoprotective effect of sildenafil against renal I/R might be due to the activation of antioxidant genes (Nrf2, HO-1 and NQO-1) and antiapoptotic gene (Bcl2) and attenuation of proinflammatory cytokines (TNF-a, IL-1β and ICAM-1).

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Acknowledgments

This work was funded by project # CEP1-031-MANS by ministry of higher education, Egypt.

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Authors and Affiliations

  1. Urology and Nephrology Center, Mansoura University, Mansoura, Egypt

    Mohamed H. Zahran, Nashwa Barakat, Amira Awadalla, Shery Khater, Ahmed Harraz & Ahmed A. Shokeir

  2. Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Abdelaziz M. Hussein

Authors
  1. Mohamed H. Zahran
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  2. Abdelaziz M. Hussein
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  3. Nashwa Barakat
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  4. Amira Awadalla
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  6. Ahmed Harraz
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  7. Ahmed A. Shokeir
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Correspondence to Abdelaziz M. Hussein.

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Authors declare that there is no any conflict of interest.

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Handling editor: Dr. Peter R. Merten.

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Zahran, M.H., Hussein, A.M., Barakat, N. et al. Sildenafil activates antioxidant and antiapoptotic genes and inhibits proinflammatory cytokine genes in a rat model of renal ischemia/reperfusion injury. Int Urol Nephrol 47, 1907–1915 (2015). https://doi.org/10.1007/s11255-015-1099-5

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  • DOI: https://doi.org/10.1007/s11255-015-1099-5

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