Morphometric study of the sensory neuron and peripheral nerve changes induced by chronic cisplatin (DDP) administration in rats

Abstract

We performed a morphological, morphometric and toxicological study on the spinal ganglia and peripheral nerves of the rat after chronic administration of cisplatin (cis-dichlorodiammineplatinum II; DDP) with two different schedules. Severe damage of the spinal ganglia neurons was demonstrated with predominant involvement of the nucleus and nucleolus associated with a decrease in the cell size. Morphological and morphometric changes also occurred in the sciatic and peroneal nerves with the features of axonopathy. All these changes were more marked in the group of rats which underwent the most intense DDP treatment and the tissue platinum concentrations were also higher in this group. This experimental model is the first available for chronic DDP administration in which concomitant spinal ganglia and peripheral nerve damage has been confirmed pathologically. Our study supports the hypothesis that DDP-induced peripheral nerve fiber degeneration may result from nuclear and nucleolar changes in the sensory ganglion cell perikaryon.

Cisplatin-incorporating polymeric micelles (NC-6004) can reduce nephrotoxicity and neurotoxicity of cisplatin in rats

“…A delay in SNCV due to the injury of dorsal root ganglia and peripheral nerve has previously been reported in rats given CDDP, although MNCV was preserved in the tail and hind paws of rats (McKeage et al, 1994;Tredici et al, 1998;Meijer et al, 1999;Tredici et al, 1999). Furthermore, histopathological examination revealed degenerative changes in the sciatic nerve in similar experimental animals (Cavaletti et al, 1992;Tredici et al, 1999). In the present study, animals given NC-6004 showed no delay in the SNCV, while animals given CDDP showed a significant delay in the SNCV as compared with animals given NC-6004.…”

“…Subsequently, a segment of the sciatic nerve was carefully removed. One part of the sciatic nerve was post-fixed with 4% glutaraldehyde in 0.12 M PBS for 24 h and was then embedded in epoxy resin as described previously (Cavaletti et al, 1992). The remaining parts of the sciatic nerve were immersed in a 10% formalin solution.…”

The signalling axis mediating neuronal apoptosis in response to [Pt(O,O′-acac)(γ-acac)(DMS)]

“…This regimen has increased the survival rates of patients with advanced neuroblastoma [2]. However, infusion with cisplatin induces peripheral neuropathy mainly affecting the large myelinated fibers of the nerves secondary to neuronopathy affecting the neurons of dorsal root ganglia [3].…”

Stereoselective peripheral sensory neurotoxicity of diaminocyclohexane platinum enantiomers related to ormaplatin and oxaliplatin

“…Previous studies of the stereoselective action of Pt(DACH) derivatives have indicated small and inconsistent differences between isomers in anti-tumour activity, and that the degree and direction of anti-tumour chiral discrimination varies between tumour Figure 1 Putative biotransformation pathways of ormaplatin and oxaliplatin (Carfagna et al, 1991;Chaney et al, 1990;Pendyala and Creaven, 1993;Gibbons et al, 1989;Maudlin et al, 1988;Petros et al, 1994) models (Kidani et al, 1978;Vollano et al, 1987;Kido et al, 1993;Siddik et al, 1993 Koning et al, 1987;Cavaletti et al, 1992) as humans (Thompson et al, 1984). Other workers have shown that the metabolism and pharmacokinetics of Pt(DACH) complexes is similar in rats and man (Carfagna et al, 1991;Petros et al, 1994).…”