Sex-related differences in cisplatin-induced neuropathy in rats.

BACKGROUND

Cisplatin is used as an anti-neoplastic agent against several cancers. Neuropathy is one of its major side effects that contributes to patients' intolerance to the standard regimen. Sex-related differences have been reported in nerve injury and neuropathies. However, there has been no study on cisplatin regarding this issue.

OBJECTIVE

Compare various abnormalities in cisplatin neuropathy between sexes.

MATERIAL AND METHOD: Two mg/kg of cisplatin was administered intraperitoneally twice a week for five consecutive weeks. Body weight, heat latency of hind paw and sciatic motor nerve conduction velocity (MNCV), pathological alterations in the sciatic nerve and dorsal root ganglion (DRG) including the level of NGF in the sciatic nerve were examined. Untreated rats of both sexes were used as controls.

RESULTS

Weight loss, prolonged heat latency, and slow MNCV in the treated rats of both sexes with higher severity in males were showed. Furthermore, reduction in myelinated fiber diameter, myelin thickness, and myelinated fiber density was more severe in females, whereas, atrophy of neuronal cell body, nucleus, and nucleolus was more striking in males. The decreased level of NGF was similar between sexes.

CONCLUSION

These data suggest the differences in various aspects of cisplatin neurotoxicity between sexes. However, future studies are needed to verify this issue in a clinical condition and clarify the underlying mechanisms.