| | Strain (breeder), | cisplatin | | Other | Ref. | | sex, age, N | dose | Time | comment | |
| | | | | Myelotoxicity | |
| | CBAxC57BLF1, female, 10-12wk, 20-25g N=3 | 12 mg/kg
ip | D1-23 | gastroenteritis and body weight loss; Femoral bone marrow, blood (WBC, RBC)
more toxic for earlier haemopoietic progenitor cells than for the mature cells. Reduction isseen after 1 day: CFU-S number dropped to 5%, and CFU-C to 6%, BFU-E to0.85%, CFU-E to 60% of the control values on D1; WBC decreased to 53% and MNC to65 % of the control values on D3. | [101] |
| | | | | Gastrointestinal toxicity | |
| Wistar
Male, 200-300g | 6 mg/kg
ip | D0-2 | Day 1: reduction in food and water intake
Day 2: ↓food intake (86%),↓water intake(78%), ↑weight of gastric contents (10x) | [137] |
| C57BL/6
Male, 8-10wk | 6 mg/kg
ip | D0-2 | Day 1: reduction in food and water intake
Day 2: ↓food intake (68%),↓water intake(45%), ↑weight of gastric contents (3x) | [137] |
| B6D2F1
Adult, male
26-30g | 8 mg/kg
10 mg/kg
12 mg/kg
14 mg/kg
ip | D1,3,6,10,14 | Weight loss was dose dependent, maximal on day 6 (11- 26%); reticulocytopenia was dose dependent with the lowest one on day 6; necrosis of renal epithelium (dose dependent) was present by day 10 posttreatment and was still apparent 21-22 days after treatment
azotemia BUN (dose dependent); dose-dependent lesions in intestinal epithelium appeared on days 1-6 (necrosis, hypertrophy, hyperplasia, and macronucleus); lesions in thecolon appeared later and were less severe. Mucosal recovery was evident by day 10 posttreatment | [132] |
| C57BL/6
8-12 wk, 20-25g N=6 | 27 mg/kg
ip | D1-3 | Villi in the small intestine shortened, reduced number of goblet cells, with increase of apoptosis
3h after cisplatin there were many apoptotic cells in the lamina propria of villi and massive apoptosis of vascular endothelial cells in the lamina propria (microvascular endothelial apoptosis) which preceded apoptosis in the epithelium (columnar epithelial cells)
Similar results were observed in the thymus: massive apoptosis of endothelial cells 3-12h after cisplatin, followed by massive apoptosis of thymocytes 36-72h after cisplatin | [138] |
| ICR
Male, Crl N=5 | 45 μmol/kg
sc | D4 | Decrease of total leucocytes, diarrhea observed in all animals | [108] |
| CBA, UK
Male, 6wk
N=15 | 10 mg/kg
ip | D10
1,3,5,7,10 | Alteration in the kinetics, morphology, and function of the mouse small intestinal mucosa.Severe depression in crypt cell production, evident by 2h and maximal between 12 and 24 h, with only a slow recovery on day 7 and marked depletion in both maltase and sucrose activity in jejunum on days 3 and 5. | [139] |
| CBA
Male, adult N=4 | 10 mg/kg
ip | D1,3,5,7,10 | Reduced height of villi and increased height of crypts in small intestine, temporary ablation of crypts, diminished mucosal function (↓disaccharidase activity) observed at D3-10 | [140] |
| Wistar, Adult
male N=15 | 10 mg/kg
ip | h1 | Mucosal damage, reduced jejunal net fluid and electrolyte absorption (sodium, potassium, chloride) | [141] |
| Wistar
Adult
male | 6 mg/kg
ip | D3 | decreased activities of the brush border membrane enzymes (alkaline phosphatase, leucine aminopeptidase, γ-glutamyltransferase) in the lining the epithelial cells of intestine, increased production of ROS and alteration in the activities of several antioxidant enzymes (↓SOD, CAT, GPx, GR,G6PD, ↑GST, TR, MDA) | [142] |
| Wistar
Male
7 months | 7 mg/kg
ip | D5 | Changed structure of crypts and villi. Enlarged crypts, reduced length of the villi and epithelium denuded, infiltration of inflammatory cells. In the colon the epithelial tissues and subepithelial layer were affected the most due to cell degeneration, laminin immunopositivity | [143] |
| | | | | Hepatotoxicity | |
| | Wistar female adult | 5 mg/kg
ip | D5 | Histological abnormalities: dispersed area of necrotic hepatocytes, inflammatory cellular infiltration, vacuolation and degeneration of hepatocytes, ↑ ALT, AST, γGT, ALP,↑ total bilirubin in serum; ↓SOD, GSH, GPx, GST, GR,↑MDA and NO, ↑expression of Cas3, Cas9, Bax in liver | [144] |
| Wistar
Male N=15 | 12 mg/kg
ip | D30 | ↑ ALT, AST, ALP, LDH, γGGT, albumin,↑ total bilirubin in serum
↓SOD, CAT, GSH, GPx, GST, GR,↑MDA, NO, TNF-α in liver | [145] |
| | | | | Testicular toxicity | |
| | Sprague-Dawley, male 8wk, 190-250g N=6 | 7 mg/kg
ip | D5
D50 | Decreased weight of testes, epididymis, accessory glands (seminal vesicles, prostate), lower sperm concentration, ↓sperm motility, head abnormalities, ↑MDA, GPx, ↓GSH activity in testes | [146, 147] |
| C57BL/6J
Male, 6-16wk, Jax | 10 mg/kg
ip | D5-31 | Changes most evident at D5: majority of tubules were devoid of the late stages of spermatogenesis. Sperm production improved by D12-18 but the decreased number of spermatogenic cells was still evident; spermatocytes and spermatid were TUNEL positive at D14-18. Reduced number of sperm/ml on D31; decreased testis size and weight. | [135] |
| | | | | Cardiotoxicity | |
| Wistar
Male, adult | 7 mg/kg
ip | D6 | ↑LDH, CK, TBARS, NO, ↓GSH, ATP
degenerative changes and vacuolated cytoplasm of many muscle cells | [134] |
| | | | | Ototoxicity | |
| | CBA/J, female Jax4-8 wk, N=5 | 14 mg/kg
ip | D8 | Hearing loss; click evoked auditory brainstem responses threshold elevation at 12± 7 dB | [148, 149] |
| Wistar
Fisher 344 | 16 mg/kg
3x5 mg/kg ip | D5 | Hearing loss, loss of cochlear outer hair cells, sensory and motor nerves conduction velocities alteration; threshold shift of more than 30 dB (at 14kHz measured by auditory evoked brain stem response); 20 dB (at 16 and 24 kHz) | [150] |
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