Effects of N Ethyl N′ nitrosourea in mice brain in time fashion

Abstract

Antioxidant enzyme plays a pivotal role in preventing oxidative stress. Chemical toxicants often exert adverse effects in the biological system by breaking the antioxidant response system leading to severe oxidative stress. N-Ethyl-N-Nitrosourea (ENU) is a DNA alkylating agent and is carcinogenic and neurotoxic in animals. ENU in the nervous system cause persistent alkylation of DNA within the neurons altering the normal functional activities of the brain. Prenatal exposure to ENU in rodents that generate malignant gliomas in the brain induces functional changes and apoptotic death in neuronal progenitors in the brain's subventricular zone (SVZ). However, as chemical toxicants, their role in the induction of oxidative stress in brain tissue and subsequent change in the brain were less studied. In this study, we have investigated the response antioxidant system and induction of oxidative stress in the Balb/c mice brain at various time points after ENU exposure. Exposures to ENU were found to raise the oxidative stress and lipid peroxidation in the brain of mice with subsequent reduction in antioxidant enzyme activity. A significant increase in lactate dehydrogenase activity in the serum and brain homogenate was recorded at 16th weeks after ENU injection, which indicates metabolic alteration due to damage in the brain and has been validated by histological damage in the cerebral cortex and abnormal neurologic behavior in animals administered with ENU.