Diethylnitrosamine Induced Oxidative Stress and Morphological Changes in The Cerebellum of Wistar Rat


  • Innocent Imosemi
  • S E Owumi


Diethylnitrosamine (DEN), a known toxin and potent carcinogen induces oxidative stress by generation of free radicals resulting in cellular injury through its metabolized end product. There is dearth of information on DEN neurotoxicity. This study therefore, evaluated the oxidative damage and morphological changes induced by DEN in the cerebellum of Wistar rat. Twenty male Wistar rats weighing between 110 and 120 g were divided into two groups (n=10). Group I rats received distilled water and served as the control group, while group II rats received 25 mg/kg body weight of DEN i.p. twice weekly for 12 weeks. At the end of the administration, the rats from both groups were weighed and killed. The brains were weighed and the cerebella dissected out, some preserved in phosphate buffered saline for oxidative stress and antioxidant markers, while others fixed in 10% formol-saline for histological and immunohistochemical (Glial fibrillary acidic protein, GFAP) studies, for cerebellar cytoarchitecture and astrocytes population, respectively. Data were analyzed employing the unpaired student’s t-test at p<0.05. There was a significant decrease in weight gain in the DEN-treated group, increased lipid peroxidation, decreased glutathione levels, superoxide dismutase activity and compared with the control rats at p<0.05. Histological and histomorphometric evaluation of the cerebellar cortex of DEN-treated rats showed pyknosis of the Purkinje cells with chromatolysis, significant reduction in the diameter/size and loss of the Purkinje cells compared with the control rats. Immunohistochemically, there was increased population of astrocytes in the DEN-treated rats compared with the control rats. The results of the study shows that prolonged exposure of rats to diethylnitrosamine induced oxidative stress with morphological alterations in the cerebellum and thus increasing the literature of diethylnitrosamine neurotoxicity


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Endocrinology/Cell Biology/ Bio-membrane/Neurosciences