Table 2.
Animal models demonstrating protective effects of iron chelators in AKI
| Reference | Animal Model | Renal Injury | Iron Chelation Regimen | Demonstration of Renal Protection | Other/ Notes | |
|---|---|---|---|---|---|---|
| BUN/Cra | Hist | |||||
| Shah et al.85 | Rats | Glycerol | DFO 30 mg/kg IV immediately before glycerol inj, then DFO 30 mg/d SC pump for 24 h | Yes | Yes | |
| Paller et al.15 | Rats | 1. Glycerol | 1. DFO 25 mg/kg per h IV for 1 h concomitantly with glycerol inj, then 12 mg/kg per h for 3 h, then 6 mg/kg per h for 3 h | Yes | NR | |
| 2. Hgb | 2. DFO 200 mg/kg per h IV for 1 h immediately after Hgb inj | Yes | NR | |||
| 3. IRI (Uni) | 3. DFO 200 mg/kg per h IV for 1 h immediately before reperfusion | Yes | NR | |||
| Paller et al.14 | Rats | IRI (Uni) | DFO 50 or 200 mg/kg per h IV infusion for 60 min starting immediately before reperfusion | Yes | Yes | Iron-saturated DFO was not protective |
| Walker et al.34 | Rats | Gent | DFO 20 mg IV immediately before gent inj, then 20 mg/d SC pump for 8 d | Yes | Yes | Iron-saturated DFO was only partially protective |
| Zager et al.21 | Rats | Glycerol | DFO 120 mg/kg IV infusion for 2 h immediately after glycerol inj; mannitol 12.5 ml/kg IV infusion for 2 h immediately after glycerol inj | Yes | Yes | DFO plus mannitol–treated rats had better functional and histologic protection compared with mannitol only |
| Gonzalez-Fajardo et al.27 | Rabbits | IRI (Bi) | DFO 25 mg/kg IV immediately before clamping and immediately before reperfusion | No | NR | |
| Ben Ismail et al.35 | Rats | Gent | DFO 100 mg/kg IM concomitantly with gent inj | No | No | |
| Haraldsson et al.28 | Rabbits | IRI (Uni) | DFO 30 mg/kg IV immediately before clamping and immediately before reperfusion; mannitol 3 ml/kg IV immediately before clamping and immediately before reperfusion | Yes | NR | DFO plus mannitol–treated rats had a higher Cr clearance compared with mannitol only |
| Watanabe et al.31 | Rats | Cisplatin | DFO 100 mg/kg IP 60 min before cisplatin and continued QD for 10 d | Yes | NR | |
| Baliga et al.12 | Rats | Cisplatin | DFO 30 mg/d SC pump starting 24 h before cisplatin and continued daily for 4 d | Yes | Yes | |
| Saad et al.86 | Rats | DXR | DFO 25, 125, 250, 375, and 500 mg/kg IP ×1 administered 30 min before DXR inj | Yes | Yes | Only rats treated with DFO at 375 or 500 mg/kg had histologic protection |
| Chander et al.87 | Rats | Glycerol | DFO 50 and 100 mg/kg SC 30 min before and 12 h after glycerol inj | Yes | Yes | Higher dose provided better renal protection |
| Ozdemir et al.32 | Mice | Cisplatin | DFO 100 and 200 mg/kg IP 60 min before cisplatin and continued QD for 10 d | Yes | Yes | GGT (marker of cisplatin toxicity) reduced by DFO |
| De Vries et al.29 | Mice | IRI (Uni) | Apotransferrin (0.1, 0.25, 0.5, and 5 mg) IP ×1 just immediately before removal of clamps | Yes | NR | |
| Naghibi et al.88 | Rats | Vanc | DHB 50 and 100 mg/kg SC inj starting 30 min before Vanc and continued QD for 7 d | Yes | Yes | |
| Bulucu et al.89 | Rats | Adriamycin (nephrotic syndrome model) | DFO 20 mg/kg IV ×1 immediately after adriamycin inj | N/A | NR | DFO compared with sham-treated rats had an attenuated rise in UPCR (Cr levels were not affected by adriamycin) |
| Petronilho et al.36 | Rats | Gent | DFO 20 mg/kg SC concomitantly with Gent inj and continued on d 1, 4, and 7; NAC 20 mg/kg SC concomitantly with Gent inj and continued q8h for 7d | Yes | NR | Rats treated with DFO plus NAC compared with either DFO or NAC alone had an attenuated rise in BUN and Cr |
| Vlahakos et al.90 | Pigs | Hepatic IRI | DFO 150 mg/kg IV infusion over 24 h starting concomitantly with hepatic artery ligation | N/A | Yes | No significant effect of ischemia or DFO on BUN and Cr |
| Bernardi et al.30 | Rats | IRI (Bi) | DFO 20 mg/kg intra-aortic inj immediately before induction of ischemia; NAC 20 mg/kg intra-aortic inj immediately before induction of ischemia | Yes | NR | Rats treated with DFO plus NAC, compared with rats treated with either DFO or NAC alone, had an attenuated rise in Cr |
| Milona-Jijón et al.91 | Rats | Chromium | DFO 100, 200, and 400 mg/kg IP administered 30 min before potassium chromium inj | Yes | Yes | Dose-dependent renal protection with higher doses of DFO; DFO administration after chromium inj was unable to attenuate nephrotoxicity |
| Sivakumar et al.37 | Mice | AlCl3 | DFP 0.72 mmol/kg PO versus combo of DFP and DFO; dosing for the latter was 0.89 mmol/kg IP starting 30 min after AlCl3 and continued QD for 5 d | Yes | Yes | Protection was seen in both DFP groups compared with sham-treated mice; however, the DFP plus DFO group had greater protection than DFP alone |
| Makhdoumi et al.33 | Rats | Cisplatin | DFP 50, 100, and 200 mg/kg PO starting 5 d before cisplatin and continued QD for 10 d | Yes | Yes | Only rats treated with DFP at 100 mg/kg, but not 50 or 200 mg/kg, were protected from nephrotoxicity |
×1 refers to a single injection. Cr, creatinine (serum or plasma); Hist, histologic; IV, intravenous; Inj, injection; SC, subcutaneous; NR, Not reported; Hgb, hemoglobin; Uni, unilateral; Gent, gentamicin; Bi, bilateral; IM, intramuscular; IP, intraperitoneal; QD, daily; DXR, doxorubicin; GGT, γ-glutamyl transferase; Vanc, vancomycin; DHB, 2,3- dihydroxybenzoic acid; N/A, Not applicable; UPCR, urine protein-creatinine ratio; AlCl3, aluminum chloride; PO, per os.
a
Refers to an attenuated rise in BUN and/or Cr compared with sham-treated animals.