Toxic effect of cisplatin on cerebellar cortex and spinal cord of adult male albino rat and the possible role of vitamin E: light and electron microscopic study

ABSTRACT

The nervous system is frequently the site of symptomatic toxicity of antineoplastic agents, cisplatin is a widely used potent chemotherapeutic agent that is highly neurotoxic. It has been proven that it is able to generate reactive oxygen species and inhibit the activity of antioxidant enzymes. This study was carried out to demonstrate the neurotoxic effects of cisplatin on the structure of adult rat cerebellum and spinal cord, and the role of vitamin E which has been shown to ameliorate hephro, oto and neurotoxicities induced by cisplatin. Thirty adult male albino rats weighing 200-250 gm were divided into three groups Group one kept as a control. Group two animals treated with cisplatin at a dose of 4mg/kg twice weekly by intraperitoneal injection, for one month. Group three animals treated with vitamin E at a dose of 100mg/kg by intramuscular injection in concomitant with cisplatin twice weekly for one month. Animals were sacrificed and their cerebella and spinal cords were processed for light and electron microscopy. Morphometrical and statistical study was done for the mean number, as well as the mean surface area of Purkinje cells and mean surface area of their nuclei. The histological approach revealed marked degenerative changes in the Purkinje cells and motor ceurons of cisplatin treated animals [Group II]. Some of these cells appeared irregular with deeply stained cytoplasm and pykontic nuclei. Ultrastructural examination showed Purkinje cells with cellular shrinkage, damaged organelles and irregular nuclei with electron dense karyoplasms. Significant degenerative changes in the motor neurons and blood capillaries of the anterior horn of the spinal cord in the same group were frequently observed. Morphometric evaluations demonstrated significant decrease in the mean number and the mean surface area of nuclei and cell bodies of Purkinje cells. These structural and morphometrical alterations were much less observed in concomitant use of vitamin E with cisplatin [Group III]. Cerebellum and spinal cord are considered the target areas of cisplatin neurotoxicity, while vitamin E, when used in combination with cisplatin displays a protective action against neurotoxicity