Cisplatin-induced neurotoxicity in cerebellar cortex of male mice involves oxidative stress and histopathology

Background: Despite evidence of neurotoxicity, cisplatin is still considered the most potent drug prescribed in human chemotherapy for a broad spectrum of malignancies. The objective was to evaluate the cerebellar cortex damage including oxidative stress biomarkers and histopathology aspects in male mice. One saline control group and two cisplatin groups were intraperitoneally injected with 0, 5, and 10 mg/kg body weight (bw) cisplatin, twice per week for four successive weeks, respectively. Results: Cisplatin decreased the body weights of treated mice. Serum levels of superoxide dismutase and glutathione peroxidase were significantly reduced in the 5 and 10 mg/kg dose, twice weekly for 4 weeks treatment; in contrast, there was a significant increase of lipid peroxidation. 5 and 10 mg/kg bw of cisplatin caused histopathological damage in the cerebellum tissue characterized by disruption, disorganization, and degeneration with dense pyknotic nuclei of the granular cells. Ultrastructurally, in the cortical region of the cerebellum, the Purkinje cells showed irregular pyknotic nuclei with indistinct nucleoli, cytoplasmic vacuolation, marked indentation of the nuclear membrane, dilatation of the endoplasmic reticulum, and breakdown and disappearance of mitochondrial cristae. Moreover, the molecular layer showed cellular necrosis and an increased number of lysosomal particles. The myelinated nerve fibers showed degenerative areas distinct by splitting, disruption, and loss of the lamellar pattern of the myelin sheath. Conclusion: These findings provide a confirmed foresight that the in vivo potential treatment of mice with cisplatin induces cerebellum deficits and impairment in neuronal histology. The identified mechanism which evokes neurotoxicity is oxidative stress-dependent status. This mechanism is pharmacologically boosted by great production of free radical reactive oxygen species.

Automated summary

Despite its potency in treating malignancies, cisplatin induces cerebellum deficits in mice leading to neuronal histological impairment, primarily through oxidative stress-dependent neurotoxicity.