Comparative neurotoxicity of oxaliplatin, cisplatin, and ormaplatin in a Wistar rat model

Oxaliplatin (4 mg/kg), cisplatin (2 mg/kg with 20 mg/kg mannitol) and ormap latin (2 mg/kg) were administered ip twice weekly for 4.5 weeks. Lactose in jections (0.9%) were used as a control for oxaliplatin and 0.9% saline inje ctions were used as a control for cisplatin and ormaplatin. Morphometric ch anges to dorsal root ganglia L4-L6 were quantitated as a measure of neuroto xicity. 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 morph ometric changes was ormaplatin > cisplatin greater than or equal to oxalipl atin. The accumulation of platinum in the DRG was measured by inductively c oupled 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 > c isplatin. This correlated with a greater retention of platinum by the DRG f or ormaplatin and oxaliplatin than for cisplatin. The results suggest that ormaplatin is uniquely neurotoxic immediately following treatment in the Wi star rat model. However, following an 8-week recovery period both ormaplati n and oxaliplatin are more neurotoxic than cisplatin and this neurotoxicity correlates with a greater retention of platinum by the DRG. (C) 1998 Socie ty of Toxicology.