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Volume 73, Issue 3, Pages 308-317 (February 2008)
Protective effect of 17β-estradiol on ischemic acute renal failure through the PI3K/Akt/eNOS pathway A. Satake, M. Takaoka, M. Nishikawa, M. Yuba, Y. Shibata, K. Okumura, K. Kitano, H. Tsutsui, K. Fujii, S. Kobuchi, M. Ohkita, Y. Matsumura Kidney International Volume 73, Issue 3, Pages (February 2008) DOI: /sj.ki Copyright © 2008 International Society of Nephrology Terms and Conditions
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Figure 1 Effects of E2-β and wortmannin (wt) on (a) BUN, (b) Pcr, (c) Ccr, (d) urine flow (UF), (e) FENa, and (f) Uosm 24 h after I/R. E2-β (100 μg kg−1, i.v.) was given 15 min before reperfusion, and wortmannin (10 μg kg−1, i.v.) was given 10 min before ischemia. Each column and bar represents the mean±s.e.m. ††P<0.01, compared with sham rats. *P<0.05, **P<0.01, compared with vehicle-treated ARF rats. Kidney International , DOI: ( /sj.ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions
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Figure 2 Light microscopy of (a-d) the inner zone of medulla, (e–h) the outer zone inner stripe, and (i–l) the outer zone outer stripe of kidneys of ARF rats treated with (b, f, and j) vehicle, (c, g, and k) E2- or (d, h, and l) E2-+wortmannin (wt), and (a, e, and i) sham-operated rats. E2-β (100 μg kg−1, i.v.) was given 15 min before reperfusion, and wortmannin (10 μg kg−1, i.v.) was given 10 min before ischemia. Arrows indicate (b and d) severe proteinaceous casts in tubuli, (f and h) congestion and hemorrhage, and (j and l) tubular necrosis (hematoxylin–eosin staining, original magnification × 200). Kidney International , DOI: ( /sj.ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions
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Figure 3 Effects of E2-β and tamoxifen (tam) on (a) BUN, (b) Pcr, (c) Ccr, (d) urine flow (UF), (e) FENa, and (f) Uosm 24 h after I/R. E2-β (100 μg kg−1, i.v.) was given 15 min before reperfusion, and tamoxifen (5 mg kg−1, i.v.) was given 60 min before ischemia. Each column and bar represents the mean±s.e.m. †P<0.01, ††P<0.01, compared with sham rats. *P<0.05, **P<0.01, compared with vehicle-treated ARF rats. Kidney International , DOI: ( /sj.ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions
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Figure 4 Time course of total Akt and phosphorylated-Akt (p-Akt, Ser473) expression in the kidney of vehicle-treated or E2-β-treated ARF rats. E2-β (100 μg kg−1, i.v.) was given 15 min before reperfusion. Mean density values are presented as fold difference compared with sham-operated rats. Each point and bar represents the mean±s.e.m. **P<0.01, compared with vehicle-treated ARF rats. Kidney International , DOI: ( /sj.ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions
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Figure 5 Time course of total eNOS and phosphorylated-eNOS (p-eNOS, Ser1177) expression in the kidney of vehicle-treated or E2-β-treated ARF rats. E2-β (100 μg kg−1, i.v.) was given 15 min before reperfusion. Mean density values are presented as fold difference compared with sham-operated rats. Each point and bar represents the mean±s.e.m. *P<0.05, **P<0.01, compared with vehicle-treated ARF rats. Kidney International , DOI: ( /sj.ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions
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Figure 6 Effects of E2-β and wortmannin (wt) on phosphorylated-Akt (p-Akt, Ser473) and phosphorylated-eNOS (p-eNOS, Ser1177) expression in the kidney 30 min after reperfusion. E2-β (100 μg kg−1, i.v.) was given 15 min before reperfusion, and wortmannin (10 μg kg−1, i.v.) was given 10 min before ischemia. (a) Representative western blots for p-Akt, total Akt, and actin. (b) Representative western blots for p-eNOS, total eNOS, and actin. Mean density values are presented as fold difference compared with vehicle-treated ARF rats. Each column and bar represents the mean±s.e.m. **P<0.01, compared with vehicle-treated ARF rats. Kidney International , DOI: ( /sj.ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions
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Figure 7 Effects of E2-β and wortmannin (wt) on phosphorylated-Akt (p-Akt, Ser473) and phosphorylated-eNOS (p-eNOS, Ser1177) expression in the kidney 60 min after reperfusion. E2-β (100 μg kg−1, i.v.) was given 15 min before reperfusion, and wortmannin (10 μg kg−1, i.v.) was given 10 min before ischemia. (a) Representative western blots for p-Akt, total Akt, and actin. (b) Representative western blots for p-eNOS, total eNOS, and actin. Mean density values are presented as fold difference compared with vehicle-treated ARF rats. Each column and bar represents the mean±s.e.m. **P<0.01, compared with vehicle-treated ARF rats. Kidney International , DOI: ( /sj.ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions
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Figure 8 Effects of E2-β and tamoxifen (tam) on phosphorylated-Akt (p-Akt, Ser473) and phosphorylated-eNOS (p-eNOS, Ser1177) expression in the kidney 30 min after reperfusion. E2-β (100 μg kg−1, i.v.) was given 15 min before reperfusion, and tamoxifen (5 mg kg−1, i.v.) was given 60 min before ischemia. (a) Representative western blots for p-Akt, total Akt, and actin. (b) Representative western blots for p-eNOS, total eNOS, and actin. Mean density values are presented as fold difference compared with vehicle-treated ARF rats. Each column and bar represents the mean±s.e.m. **P<0.01, compared with vehicle-treated ARF rats. Kidney International , DOI: ( /sj.ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions
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Figure 9 Effects of E2-β and tamoxifen (tam) on phosphorylated-Akt (p-Akt, Ser473) and phosphorylated-eNOS (p-eNOS, Ser1177) expression in the kidney 60 min after reperfusion. E2-β (100 μg kg−1, i.v.) was given 15 min before reperfusion, and tamoxifen (5 mg kg−1, i.v.) was given 60 min before ischemia. (a) Representative western blots for p-Akt, total Akt, and actin. (b) Representative western blots for p-eNOS, total eNOS, and actin. Mean density values are presented as fold difference compared with vehicle-treated ARF rats. Each column and bar represents the mean±s.e.m. **P<0.01, compared with vehicle-treated ARF rats. Kidney International , DOI: ( /sj.ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions
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Figure 10 Time course of renal blood flow in the post-ischemic kidneys with or without E2-β treatment. E2-β (100 μg kg−1, i.v.) was given 15 min before reperfusion. Each point and bar represents the mean±s.e.m. *P<0.05, compared with vehicle-treated ARF rats. Kidney International , DOI: ( /sj.ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions
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Figure 11 Effects of E2-β on (a) BUN and (b) Pcr 48 h after I/R in wild-type mice and eNOS−/- mice. E2-β (100 μg kg−1, i.v.) was given 15 min before reperfusion. Each column and bar represents the mean±s.e.m. *P<0.05, **P<0.01, compared with vehicle-treated ARF mice. Kidney International , DOI: ( /sj.ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions
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Figure 12 Effects of E2-β on (a) BUN and (b) Pcr 24 h after I/R in bilateral ischemia models. E2-β (10–100 μg kg−1, i.v.) was given 15 min before reperfusion. Each column and bar represents the mean±s.e.m. *P<0.05, **P<0.01, compared with vehicle-treated ARF rats. Kidney International , DOI: ( /sj.ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions
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