Experimental cisplatin neuronopathy in rats and the effect of retinoic acid administration

Peripheral nervous system alterations were induced in adult rats by administration of cisplatin (CDDP) 2 mg/kg twice weekly for 4.5 weeks. Dorsal root ganglion neurons showed pathological changes. Morphometric determinations demonstrated a reduction in size of the somatic, nuclear and nucleolar area. The nucleoli were the most involved subcellular structures. Nerve conduction velocity and the tail-flick test for pain were both significantly altered in CDDP treated rats, whereas the rota-rod test for coordination revealed no changes in either treated or control rats. Analytical determinations demonstrated platinum accumulation in the DRG of CDDP treated rats. Spontaneous recovery, demonstrated by morphometric, electrophysiological, functional and analytical determinations, occurred after treatment discontinuation within about 7 weeks. A pilot study of the possible neuroprotective action of retinoic acid (RA) was also performed with this model of cisplatin neuronopathy. The rationale for using RA was based on its assumed antioxidant and neurotrophic effect. However, RA failed to prevent morphometric, electrophysiological, functional and analytical alterations induced by CDDP on DRG neurons. RA induced only a mild generalized protective effect.