1. Volume 63, Issue 1, Pages 134-142 (January 2003)
A small molecule C5a receptor antagonist protects kidneys from ischemia/reperfusion injury in rats 
Thiruma V. Arumugam, Ian A. Shiels, Anna J. Strachan, Giovani Abbenante, David P. Fairlie, Stephen M. Taylor 
Kidney International 
Volume 63, Issue 1, Pages (January 2003)
DOI: /j x
Copyright © 2003 International Society of Nephrology Terms and Conditions

2. Figure 1
Plasma concentrations of creatinine and aspartate aminotransferase (AST) after renal ischemia/reperfusion (I/R) injury. Renal I/R caused significant elevation of both plasma creatinine (A) and AST concentrations (B) compared with sham-operated animals. Rats pretreated with the C5aR antagonist AcF-[OPdChaWR] either 1 mg/kg IV or 10 mg/kg PO showed a significant reduction in plasma creatinine or AST compared to I/R animals. Data are shown as means ± SEM (N = 6 to 15 in each group). Symbols are: (□) Sham; () Sham + 1 mg/kg IV AcF-[OPdChaWR]; (▪) I/R injury; () I/R +1 mg/kg IV AcF-[OPdChaWR]; () I/R + 10mg/kg PO AcF-[OPdChaWR]. *P < vs. sham-operated animals; +P < vs. I/R animals.
Kidney International  , DOI: ( /j x)
Copyright © 2003 International Society of Nephrology Terms and Conditions

3. Figure 2
Renal I/R induced urinary leukocytes. Renal I/R caused a significant increase in urine leukocyte counts compared with sham-operated animals, which had no detectable leukocytes in the urine. Pretreatment of rats with the C5aR antagonist AcF-[OPdChaWR] with either 1 mg/kg IV or 10 mg/kg PO blocked I/R-induced urinary leukocytes. Data are shown as means ± SEM (N = 4 to 6 in each group). Symbols are: (□) Sham; () Sham + 1 mg/kg IV AcF-[OPdChaWR]; (▪) I/R injury; () I/R + 1 mg/kg IV AcF-[OPdChaWR]; () I/R + 10 mg/kg PO AcF-[OPdChaWR]. *P < vs. sham-operated animals, +P < vs. I/R animals.
Kidney International  , DOI: ( /j x)
Copyright © 2003 International Society of Nephrology Terms and Conditions

4. Figure 3
Renal I/R-induced microvascular permeability measured by Evans blue extravasation. Rats with I/R showed a significant increase in Evans blue leakage compared with sham-operated animals. Pretreatment of rats with the C5aR antagonist AcF-[OPdChaWR] either 1 mg/kg IV or 10 mg/kg PO significantly reduced Evans blue leakage compared to I/R animals. Data are shown as means ± SEM (N = 6 to 9 in each group). Symbols are: (□) Sham; () Sham + 1 mg/kg IV AcF-[OPdChaWR]; (▪) I/R injury; () I/R +1 mg/kg IV AcF-[OPdChaWR]; () I/R + 10 mg/kg PO AcF-[OPdChaWR]. *P < vs. sham-operated animals, +P < vs. I/R animals.
Kidney International  , DOI: ( /j x)
Copyright © 2003 International Society of Nephrology Terms and Conditions

5. Figure 4
Renal I/R induced tissue TNF-α. Renal I/R resulted in significant elevation in tissue TNF-α compared with sham-operated animals. Rats pretreated with the C5aR antagonist AcF-[OPdChaWR] at either 1 mg/kg IV or 10 mg/kg PO showed inhibition of the elevation of tissue TNF-α levels compared with I/R animals. Data are shown as means ± SEM (N = 4 to 6 in each group). Symbols are: (□) Sham; () Sham + 1 mg/kg IV AcF-[OPdChaWR]; (▪) I/R injury; () I/R + 1 mg/kg IV AcF-[OPdChaWR]; () I/R + 10 mg/kg PO AcF-[OPdChaWR]. *P < vs. sham-operated animals, +P < vs. I/R animals.
Kidney International  , DOI: ( /j x)
Copyright © 2003 International Society of Nephrology Terms and Conditions

6. Figure 5
Renal tissue MPO activity. Renal I/R resulted in significant elevation in tissue MPO activity compared with sham-operated animals. Rats pretreated with the C5aR antagonist AcF-[OPdChaWR] at either 1 mg/kg IV or 10 mg/kg PO had reduced tissue MPO activity compared with I/R animals. Data are shown as means ± SEM (N = 5 to 10 in each group). Symbols are: (□) Sham; () Sham + 1 mg/kg IV AcF-[OPdChaWR]; (▪) I/R injury; () I/R + 1 mg/kg IV AcF-[OPdChaWR]; () I/R + 10 mg/kg PO AcF-[OPdChaWR]. *P < vs. sham-operated animals, +P < vs. I/R animals.
Kidney International  , DOI: ( /j x)
Copyright © 2003 International Society of Nephrology Terms and Conditions

7. Figure 6
Histological analysis of I/R-induced renal tissue injury. Microscopic images of renal tissue sections are from (A) sham, (B) I/R, (C) 1 mg/kg IV AcF-[OPdChaWR]+ I/R, and (D) 10 mg/kg PO AcF-[OPdChaWR]+ I/R groups. Large arrow indicates hemorrhage in the renal parenchyma and small arrowheads indicate peritubular edema of the distal tubules. Sections of 5 μm were stained with hematoxylin-eosin and the original magnification was ×200.
Kidney International  , DOI: ( /j x)
Copyright © 2003 International Society of Nephrology Terms and Conditions

8. Figure 7
Numerical score of the degree of pathological change in kidneys. Renal I/R resulted in damage to the renal tissue compared to sham-operated animals. Pretreatment with the C5aR antagonist AcF-[OPdChaWR] at either 1 mg/kg IV or 10 mg/kg reduced renal I/R-induced tissue damage compared to I/R animals. Data are shown as means ± SEM (N = 6 to 10 in each group). Symbols are: (□) Sham; () Sham + 1 mg/kg IV AcF-[OPdChaWR]; (▪) I/R injury; () I/R + 1 mg/kg IV AcF-[OPdChaWR]; () I/R + 10 mg/kg PO AcF-[OPdChaWR].
Kidney International  , DOI: ( /j x)
Copyright © 2003 International Society of Nephrology Terms and Conditions

9. Figure 8
Unimpaired MAC activity. Effect of AcF-[OPdChaWR] on hemolysin-induced RBC lysis. The C5a antagonist AcF-[OPdChaWR] at concentrations up to 100 μmol/L had no effect on RBC lysis. Rosmarinic acid (100 μmol/L) inhibited RBC lysis by ∼70%. Symbols are: (○) AcF-[OPdChaWR]; (•) Rosmarinic acid.
Kidney International  , DOI: ( /j x)
Copyright © 2003 International Society of Nephrology Terms and Conditions