Review Article

Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges

Table 4

Clinical alterations and the toxicity of cisplatin in rats.

strain 
(breeder)
age R cisplatin
dose
TPBUN
mg/dl
Cr  
mg/dl
endMhistology and other commentsRef.
sex 
N

Han-Wistar 
(Harlan)
7wks 
female 
N=10
ip2.5 mg/kgD5 
D8 
D22
Ns 
Ns 
ns
Ns 
Ns 
ns
D220%Various doses (0.1; 1; 2.5mg/kg): the effects appeared in a temporal and dose-dependent manner; Histology: D5: mild ATN, D8: minimal ATN, D22: regeneration; majority of alteration seen in the S3 segment of proximal tubules, rarely in distal tubules and collecting ducts[122, 123]

Han-Wistar 
(Crl)
7wks 
Male 
N=10
ip3 mg/kgD2 
D3 
D5
Ns 
Ns 
↑3.5x
Ns 
Ns 
↑2.5x
D50%Histology: D2,D3,D5: moderate ATN,  
Urine: ↑leukocytes, ↑ total protein (5.6x)
[104]

Sprague-Dawley 
(Crl)
6wks 
Male 
N=10
ip3 mg/kgD2 
D3 
D5
Ns 
↑1.37x 
↑2.2x
Ns 
↑1.25x 
↑2.4x
D50%Histology: D3-D5: minimal to moderate degeneration/necrosis of the S3 segment of proximal tubules in less than half of rats 
Urine: ↑leukocytes, ↑ total protein (4.6x)
[104]

Wistar 
WKY 
(Spain)
7wks 
female 
N=4
ip5 mg/kgD5↑2x↑3.5xD50%Histology: tubule swelling, loss of brush border membrane, epithelial vacuolization, hyaline casts and cell debris detachment in proximal tubular cells; ↓GFR 3.3x 
Urine:↑volume (1.9x), proteins (1.9x)
[36, 124]

Wistar 
( Spain)
7wks 
male 
 N=8
ip5mg/kgD5↑2.4x↑3.3xD50%Histology: tubular necrosis, swelling and tubular
dilatation, extensive epithelial vacuolization,
hyaline casts in tubules;  
↓BW (8.5%); ↓GFR (4.1x)  
Urine: ↑Na+, ↑volume (2x), ↑proteins (1.7x), ↑urine hydrogen peroxide production, ↓antioxidant capacity in urine
[54]

F344 
(NIH)
Male 
N=7-45
ip6 mg/kgD1 
D2 
D3 
D4 
D5 
D7
Ns 
↑1.5x 
↑4x 
↑3.5x 
↑5.3x 
↑3.2x
Ns 
Ns 
↑3.7x 
↑4.7x 
↑4.7x 
↑2.6x
D70%↓5 g of BW per day;  
Histology: D3: focal area of mild ATN in proximal tubules: loss of the brush border, necrotic cells sloughing into the tubular lumen, condensed cytoplasm of many cells, increased number of cytoplasmic vesicles in injured cells;  
D5: widespread moderate ATN in proximal as and distal tubules: desquamation of necrotic cells, patches of denuded basement membrane, necrotic debris filling the tubular lumens and hyaline casts. Some cells show similar changes as those at D3, lower in height, brush border loss, increased vesicles and swelling;  
D7: first signs of regeneration, necrotic cells and necrotic debris are still present
[10, 32]

Sprague Dawley 
(Turkey)
8wk,  
Male 
N=6
ip7 mg/kgD5107±5.11.4±0.16D50%Histology: necrosis in proximal tubules, karyomegaly, hyaline casts, desquamation and parenchyma degeneration of tubular epithelial cells, interstitial nephritis;  
↓BW (9%); ≈plasma Na+ and K+
Kidney: ↓GSH, GPx, CAT, ↑MDA
[125]

Wistar 
(Turkey)
200-250g 
female 
N=10
ip7 mg/kgD5↑8x↑4.5xD50%Histology: D5: extensive epithelial cell vacuolization, swelling and desquamation 
Kidney: ↓ SOD, CAT, GPx,↑ MDA, MPO
[126]

Wistar Hanover 
(Harlan)
male 
N=5
iv8 mg/kgD3 
D5
↑2x 
↑5.5x
↑1.3x 
↑6.5x
D50%Histology: D5: widespread tubular degeneration and regeneration, tubules contained granular and proteinaceous casts, mineralization (5/5)  
D3: ↑AST (1.2x), urine proteins, glycosuria 
D5:↓AST, TBIL, GGT, ALP, CI; ↑urine proteins, glycosuria
[64]

Wistar Hanover 
(Harlan)
male 
N=5
iv4x 1 mg/kgD3 
D5
ns 
ns
ns 
ns
D50%Histology: D5: similar to 8 mg/kg but less extensive (5/5)[64]

Nephrotoxicity and antitumor activity in rats with cancer

ratsN=3-5iv5mg/kgD3 
D6
51±10 (↑2x)  
56±20 (↑2x) /
D60%↓5% BW [127]

ratsN=3-5ip3 x 2.5 mg/kg dailyD3 
D6
34±4 (↑0.5x)  
73±28 (↑3x)) /
D60%↓17% BW [127]

ratsN=3-5ip7.5 mg/kgD3 
D6
60±10(↑0.2x)  
216±82 (↑8x) /
D60%↓22% BW [127]

N: number; M: mortality; R: route of injection; TP: time point; ip: intraperitoneally; iv: intravenously; sc: subcutaneously; D: day; ≈: ns; ↓: decrease; ↑: increase; BUN: blood urea nitrogen; Cr: serum creatinine; GFR: glomerular filtration rate; ATN: acute tubular necrosis; HEP: humane endpoint (animals were humanely euthanized due to severe illness).