Does cyclooxygenase-2 inhibitor prevent renal tissue damage in unilateral ureteral obstruction?

Akira Miyajima, Keiichi Ito, Takako Asano, Kaori Seta, Akinobu Ueda, Masamichi Hayakawa

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Purpose: We determined whether the cyclooxygenase-2 inhibitor etodolac affects renal tubular damage and interstitial fibrosis in unilateral ureteral obstruction. Materials and Methods: Etodolac (10 mg./kg.) was administered to rats 1 day before unilateral ureteral obstruction and every day thereafter. Kidneys were harvested at day 14 after unilateral ureteral obstruction. Tissue transforming growth factor-β and prostaglandin E2 were measured by bioassay using mink lung epithelial cells and enzyme linked immunosorbent-sandwich assay. Renal tubular proliferation and apoptosis were detected by immunostaining with proliferating cellular nuclear antigen and by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling, respectively. Cyclooxygenase-2 expression was detected by immunohistochemistry. Fibrosis was assessed by measuring collagen deposition in trichrome stained slides. Results: Bioassay showed that in the control group obstructed kidneys contained significantly higher mean transforming growth factor-β1 than unobstructed kidneys (79.1 ± 8.3 versus 33.6 ± 4.2 ng./gm. tissue) and etodolac significantly decrease the mean value in obstructed kidneys (46.2 ± 10.0 ng./gm. tissue). Assay demonstrated that obstructed control kidneys had significantly more mean tubular apoptosis than their unobstructed counterparts (26.6 ± 5.4 versus 2.2 ± 1.4 nuclei per high power field) and etodolac significantly decreased mean renal tubular apoptosis in the obstructed kidneys (16.2 ± 1.9 nuclei per high power field). In addition, immunostaining with proliferating cellular nuclear antigen showed that obstructed kidneys in the control group had significantly more mean renal tubular proliferation than unobstructed kidneys (9.8 ± 3.4 versus 3.9 ± 0.1 per high power field) and etodolac significantly increased mean proliferating renal tubule in the obstructed kidneys (24.9 ± 4.3 per high power field). Control obstructed kidneys had significantly more fibrosis and prostaglandin E2 production, which were also significantly blunted by etodolac. Conclusions: The cyclooxygenase-2 inhibitor etodolac significantly reduces tissue transforming growth factor-β, resulting in decreased tubular damage and interstitial fibrosis. This finding suggests that etodolac is a promising agent for preventing renal tissue damage in unilateral ureteral obstruction.

Original languageEnglish
Pages (from-to)1124-1129
Number of pages6
JournalJournal of Urology
Volume166
Issue number3
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Ureteral Obstruction
Cyclooxygenase 2 Inhibitors
Etodolac
Kidney
Transforming Growth Factors
Fibrosis
Nuclear Antigens
Apoptosis
Dinoprostone
Biological Assay
Renal Agents
Mink
Control Groups
DNA Nucleotidylexotransferase
Cyclooxygenase 2

Keywords

  • Apoptosis
  • Cyclooxygenase inhibitors
  • Rats, Sprague-Dawley
  • Ureteral obstruction

ASJC Scopus subject areas

  • Urology

Cite this

Miyajima, A., Ito, K., Asano, T., Seta, K., Ueda, A., & Hayakawa, M. (2001). Does cyclooxygenase-2 inhibitor prevent renal tissue damage in unilateral ureteral obstruction? Journal of Urology, 166(3), 1124-1129.

Does cyclooxygenase-2 inhibitor prevent renal tissue damage in unilateral ureteral obstruction? / Miyajima, Akira; Ito, Keiichi; Asano, Takako; Seta, Kaori; Ueda, Akinobu; Hayakawa, Masamichi.

In: Journal of Urology, Vol. 166, No. 3, 2001, p. 1124-1129.

Research output: Contribution to journalArticle

Miyajima, A, Ito, K, Asano, T, Seta, K, Ueda, A & Hayakawa, M 2001, 'Does cyclooxygenase-2 inhibitor prevent renal tissue damage in unilateral ureteral obstruction?', Journal of Urology, vol. 166, no. 3, pp. 1124-1129.
Miyajima A, Ito K, Asano T, Seta K, Ueda A, Hayakawa M. Does cyclooxygenase-2 inhibitor prevent renal tissue damage in unilateral ureteral obstruction? Journal of Urology. 2001;166(3):1124-1129.
Miyajima, Akira ; Ito, Keiichi ; Asano, Takako ; Seta, Kaori ; Ueda, Akinobu ; Hayakawa, Masamichi. / Does cyclooxygenase-2 inhibitor prevent renal tissue damage in unilateral ureteral obstruction?. In: Journal of Urology. 2001 ; Vol. 166, No. 3. pp. 1124-1129.
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abstract = "Purpose: We determined whether the cyclooxygenase-2 inhibitor etodolac affects renal tubular damage and interstitial fibrosis in unilateral ureteral obstruction. Materials and Methods: Etodolac (10 mg./kg.) was administered to rats 1 day before unilateral ureteral obstruction and every day thereafter. Kidneys were harvested at day 14 after unilateral ureteral obstruction. Tissue transforming growth factor-β and prostaglandin E2 were measured by bioassay using mink lung epithelial cells and enzyme linked immunosorbent-sandwich assay. Renal tubular proliferation and apoptosis were detected by immunostaining with proliferating cellular nuclear antigen and by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling, respectively. Cyclooxygenase-2 expression was detected by immunohistochemistry. Fibrosis was assessed by measuring collagen deposition in trichrome stained slides. Results: Bioassay showed that in the control group obstructed kidneys contained significantly higher mean transforming growth factor-β1 than unobstructed kidneys (79.1 ± 8.3 versus 33.6 ± 4.2 ng./gm. tissue) and etodolac significantly decrease the mean value in obstructed kidneys (46.2 ± 10.0 ng./gm. tissue). Assay demonstrated that obstructed control kidneys had significantly more mean tubular apoptosis than their unobstructed counterparts (26.6 ± 5.4 versus 2.2 ± 1.4 nuclei per high power field) and etodolac significantly decreased mean renal tubular apoptosis in the obstructed kidneys (16.2 ± 1.9 nuclei per high power field). In addition, immunostaining with proliferating cellular nuclear antigen showed that obstructed kidneys in the control group had significantly more mean renal tubular proliferation than unobstructed kidneys (9.8 ± 3.4 versus 3.9 ± 0.1 per high power field) and etodolac significantly increased mean proliferating renal tubule in the obstructed kidneys (24.9 ± 4.3 per high power field). Control obstructed kidneys had significantly more fibrosis and prostaglandin E2 production, which were also significantly blunted by etodolac. Conclusions: The cyclooxygenase-2 inhibitor etodolac significantly reduces tissue transforming growth factor-β, resulting in decreased tubular damage and interstitial fibrosis. This finding suggests that etodolac is a promising agent for preventing renal tissue damage in unilateral ureteral obstruction.",
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AU - Ueda, Akinobu

AU - Hayakawa, Masamichi

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N2 - Purpose: We determined whether the cyclooxygenase-2 inhibitor etodolac affects renal tubular damage and interstitial fibrosis in unilateral ureteral obstruction. Materials and Methods: Etodolac (10 mg./kg.) was administered to rats 1 day before unilateral ureteral obstruction and every day thereafter. Kidneys were harvested at day 14 after unilateral ureteral obstruction. Tissue transforming growth factor-β and prostaglandin E2 were measured by bioassay using mink lung epithelial cells and enzyme linked immunosorbent-sandwich assay. Renal tubular proliferation and apoptosis were detected by immunostaining with proliferating cellular nuclear antigen and by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling, respectively. Cyclooxygenase-2 expression was detected by immunohistochemistry. Fibrosis was assessed by measuring collagen deposition in trichrome stained slides. Results: Bioassay showed that in the control group obstructed kidneys contained significantly higher mean transforming growth factor-β1 than unobstructed kidneys (79.1 ± 8.3 versus 33.6 ± 4.2 ng./gm. tissue) and etodolac significantly decrease the mean value in obstructed kidneys (46.2 ± 10.0 ng./gm. tissue). Assay demonstrated that obstructed control kidneys had significantly more mean tubular apoptosis than their unobstructed counterparts (26.6 ± 5.4 versus 2.2 ± 1.4 nuclei per high power field) and etodolac significantly decreased mean renal tubular apoptosis in the obstructed kidneys (16.2 ± 1.9 nuclei per high power field). In addition, immunostaining with proliferating cellular nuclear antigen showed that obstructed kidneys in the control group had significantly more mean renal tubular proliferation than unobstructed kidneys (9.8 ± 3.4 versus 3.9 ± 0.1 per high power field) and etodolac significantly increased mean proliferating renal tubule in the obstructed kidneys (24.9 ± 4.3 per high power field). Control obstructed kidneys had significantly more fibrosis and prostaglandin E2 production, which were also significantly blunted by etodolac. Conclusions: The cyclooxygenase-2 inhibitor etodolac significantly reduces tissue transforming growth factor-β, resulting in decreased tubular damage and interstitial fibrosis. This finding suggests that etodolac is a promising agent for preventing renal tissue damage in unilateral ureteral obstruction.

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