1. Volume 76, Issue 3, Pages 277-285 (August 2009)
Transcription factor Nrf2 is protective during ischemic and nephrotoxic acute kidney injury in mice 
Manchang Liu, Dmitry N. Grigoryev, Michael T. Crow, Mark Haas, Masayuki Yamamoto, Sekhar P. Reddy, Hamid Rabb 
Kidney International 
Volume 76, Issue 3, Pages (August 2009)
DOI: /ki
Copyright © 2009 International Society of Nephrology Terms and Conditions

2. Figure 1
Up/downregulated Nrf2 antioxidant genes in the ischemic kidney. Nrf2+/+ (wild type) and Nrf2−/− (deficient) mice underwent renal ischemia followed by reperfusion for 24h. Total RNA was isolated from the collected kidneys and processed for gene microarray. The data is expressed as a fold change of each gene in ischemic kidney from wild-type mice over that from Nrf2−/− mice (a) or each gene in ischemic kidney over that in sham-operated kidney (b). (*P<0.05 vs Nrf2−/−). Gene symbols: Aldh1a1 (7), aldehyde dehydrogenase family 1, subfamily A1 (7); Gadd45, growth arrest/DNA-damage-inducible 45; Gclc (m), glutamate-cysteine ligase, catalytic (modified) subunit; Gpx2(3), glutathione peroxidase 2 (3); Gsr, glutathione reductase 1; Gsta2, glutathione S-transferase, α-2; Gstm4(5), glutathione S-transferase, mu 4 (5); Gstp1, glutathione S-transferase, pi 1; Hmox1, heme oxygenase (decycling) 1; Nqo1, NAD(P)H dehydrogenase, quinone 1; Txnrd1, thioredoxin reductase 1.
Kidney International  , DOI: ( /ki )
Copyright © 2009 International Society of Nephrology Terms and Conditions

3. Figure 2
Comparison of renal function, kidney histology, kidney vascular permeability, and survival in Nrf2+/+ and Nrf2−/− mice after renal ischemia. All mice underwent 30 (a–d) or 60 (d) min bilateral renal ischemia followed by reperfusion for up to 72h. Serum creatinine (SCr), Evans blue dye extravasations (EBDE), tubular injury score and mouse survival was analyzed. (a: SCr. *P<0.02 vs Nrf2+/+, n=6; b: EBDE. *P<0.03 vs Nrf2+/+, n=6–8; c: tubular injury score. *P<0.03 vs Nrf2+/+, n=7; d: survival. *P=0.008 vs Nrf2+/+ 60min by log-rank test. n=7–17 in 60min ischemia; n=5–6 in 30min).
Kidney International  , DOI: ( /ki )
Copyright © 2009 International Society of Nephrology Terms and Conditions

4. Figure 3
Photomicrographs of kidney histology from Nrf2+/+ mice and Nrf2−/− mice. All mice underwent either 30min bilateral renal ischemia or sham operation and were killed 72h later. The collected kidneys were stained with H&E for histological examination. Nrf2−/− mice had more tubular injury than Nrf2+/+ mice after ischemia. (a and e: sham kidney from Nrf2+/+ mice; b and f: sham kidney from Nrf2−/− mice; c and g: ischemic kidney from Nrf2+/+ mice; d and h: ischemic kidney from Nrf2−/− mice. Asterisks indicate dilated tubules or cast formation. Arrows, necrotized tubules).
Kidney International  , DOI: ( /ki )
Copyright © 2009 International Society of Nephrology Terms and Conditions

5. Figure 4
Cytokine and chemokine proteins in the kidney. All mice underwent 30min renal ischemia or sham operation and were killed at 72h after surgery. Total protein was extracted from the kidneys and measured for cytokine and chemokine using Bio-plex protein array. The data are presented as fold of change (FOC) of each cytokine or chemokine in ischemic kidney over that in sham-operated kidney on a semi-log scale. (*P=0.05; **P=0.06 vs Nrf2+/+, n=6–8 per group).
Kidney International  , DOI: ( /ki )
Copyright © 2009 International Society of Nephrology Terms and Conditions

6. Figure 5
Effect of GSH or NAC treatment on renal function and tubular injury score after ischemia. All mice were pretreated with either GSH (5mM/kg/d i.p.) for 3 days, or NAC (500mg/kg i.p.) 24h or equal volume of saline before renal ischemia. Mice were killed at 24h after surgery and serum creatinine concentration (a and b) was measured as the marker of renal function and kidney tubular injury score (c and d) was evaluated. a: SCr in Nrf2−/− mice. *P<0.001 and **P<0.003 vs saline, n=6–13; c: *P=0.011 and **P=0.003 vs saline, n=6–12; d: *P=0.021 vs saline, n=3–10. Epi: epithelium; PMN: polymorphonuclear leukocyte.
Kidney International  , DOI: ( /ki )
Copyright © 2009 International Society of Nephrology Terms and Conditions

7. Figure 6
Effect of NAC treatment on ischemic kidney cytokines and chemokines. All mice were pretreated with either NAC (500mg/kg, i.p.) or saline 24h before renal ischemia. The total protein was extracted from the harvested kidneys and processed for cytokine/chemokine protein array. a: Nrf2−/− mice, *P=0.004 vs saline; n=8–10. b: Nrf2+/+ mice. *P=0.04 vs saline; n=3–8.
Kidney International  , DOI: ( /ki )
Copyright © 2009 International Society of Nephrology Terms and Conditions

8. Figure 7
Renal function and survival after lower dose of cisplatin. All mice were injected with cisplatin i.p. at 20mg/kg and were followed up to 1 week. Serum creatinine concentration (a) was measured at an indicated time and the accumulative survival (b) was analyzed. (a: *P<0.05, n=4–5; b: **P<0.02 by log-rank test).
Kidney International  , DOI: ( /ki )
Copyright © 2009 International Society of Nephrology Terms and Conditions

9. Figure 8
Effect of NAC pretreatment on higher dose of cisplatin-induced renal dysfunction. All mice pretreated with either NAC (500mg/kg i.p.) or saline 24h before cisplatin injection (30mg/kg, i.p.) and serum creatinine concentration was measured. (*P<0.001 vs Nrf2+/+ saline; **P=0.002 vs Nrf2−/− saline; n=5 per group).
Kidney International  , DOI: ( /ki )
Copyright © 2009 International Society of Nephrology Terms and Conditions