An ultrastructural study of neuronal changes in dorsal root ganglia (DRG) of rats after chronic cisplatin administrations

Abstract

ln humans, the main dose-limiting side-effect of cisplatin (CDDP) treatment is a peripheral sensory neuropathy secondary to dorsal root ganglion (DRG) neuron involvement. To investigate further for neuronal alterations responsible for CDDP neurotoxicity we undertook the present experimental ultrastructural study, based on observations of 3 different groups of rats (6 animals in each group). Group A rats were treated with 1 mg/kg weekly for 9 weeks: Group B with 2 mglkg weekly for 9 weeks; and group C rats served as untreated controls. At the end of the experiment, rats were perfused with 3% glutaraldehyde and lumbar DRGs were prepared for electron microscopic observations. In CDDP-treated rats somatic, nuclear and. above all, nucleolar size was reduced. Ultrastructurally, the nucleolus was the most affected structure. Nucleolar alterations were quantified morphometrically. Less marked changes were seen in the nucleus and in the RER and Golgi apparatus of the cytoplasm. The number of lysosomes and lipofuscins was greatly increased in CDDP-treated rats. The ultrastructural alterations observed in CDDP rats suggest that CDDP may be neurotoxic due to a reduction in protein synthesis. This assumption would explain why cells such as neurons, which are non replicating, but which have a high rate of protein synthesis, may be the target of the neurotoxic action of CDDP. The lack of an efficient blood/nerve barrier in the DRG explains the involvement of this particular type of neuron.