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| Comparative neurotoxicity of oxaliplatin, cisplatin, and ormaplatin in a Wistar rat model |
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| Author(s): Holmes J, Stanko J, Varchenko M, Ding H, Madden VJ, Bagnell CR, Wyrick SD, Chaney SG |
| Source: TOXICOLOGICAL SCIENCES Volume: 46 Issue: 2 Pages: 342-351 Published: DEC 1998 |
| Times Cited: 46 References: 36 |
| Abstract: Oxaliplatin (4 mg/kg), cisplatin (2 mg/kg with 20 mg/kg mannitol) and ormaplatin (2 mg/kg) were administered ip twice weekly for 4.5 weeks. Lactose injections (0.9%) were used as a control for oxaliplatin and 0.9% saline injections were used as a control for cisplatin and ormaplatin. Morphometric changes to dorsal root ganglia L4-L6 were quantitated as a measure of neurotoxicity. Drug treatment resulted in a decrease in cell and nuclear area and an increase in the percentage of cells with eccentric nucleoli for neuronal cell bodies in the DRG. Immediately following treatment the order of morphometric changes was ormaplatin > cisplatin greater than or equal to oxaliplatin. The accumulation of platinum in the DRG was measured by inductively coupled plasma mass spectrometry. The order of accumulation was cisplatin > oxaliplatin > ormaplatin. Following an 8-week recovery period the order of morphometric changes to the DRG was ormaplatin congruent to oxaliplatin > cisplatin. This correlated with a greater retention of platinum by the DRG for ormaplatin and oxaliplatin than for cisplatin. The results suggest that ormaplatin is uniquely neurotoxic immediately following treatment in the Wistar rat model. However, following an 8-week recovery period both ormaplatin and oxaliplatin are more neurotoxic than cisplatin and this neurotoxicity correlates with a greater retention of platinum by the DRG. (C) 1998 Society of Toxicology. |
| Document Type: Article |
| Language: English |
| Reprint Address: Holmes, J (reprint author), Univ N Carolina, Dept Biophys & Biochem, Curriculum Toxicol, Chapel Hill, NC 27599 USA |
Addresses:
1. Univ N Carolina, Dept Biophys & Biochem, Curriculum Toxicol, Chapel Hill, NC 27599 USA
2. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
3. Res Triangle Inst, Inorgan Chem Lab, Res Triangle Pk, NC 27709 USA
4. Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Microscopy Serv Lab, Chapel Hill, NC 27599 USA
5. Univ N Carolina, Sch Pharm, Div Med & Nat Prod Chem, Chapel Hill, NC 27599 USA |
| Publisher: OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND |
| Subject Category: Toxicology |
| IDS Number: 167FX |
| ISSN: 1096-6080 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |