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© 1998 Oxford University Press
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Comparative Neurotoxicity of Oxaliplatin, Cisplatin, and Ormaplatin in a Wistar Rat Model1
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*Department of Biochemistry and Biophysics, Curriculum in Toxicology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599
Inorganic Chemistry Laboratory, Analytical and Chemical Sciences, Research Triangle Institute Research Triangle Park, North Carolina
Microscopy Services Laboratory, Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina Chapel Hill, North Carolina 27599
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina Chapel Hill, North Carolina 27599
Received March 30, 1998; accepted August 7, 1998
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 
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 
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.
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