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.

N-Ethyl-N-Nitrosourea Induced Leukaemia in a Mouse Model: Protective Effect of Icaritin via Inhibition of IL-6/JAK2/STAT3 Pathway Causes Apoptosis

“… 30 , 31 ENU has also been observed to generate malignant cells in the brain and reproductive system in animal models. 4 , 32 Any disruption in the signaling cascade that regulates differentiation and proliferation can lead to hematological abnormalities, resulting in a buildup of cancerous cells in the bone marrow and blood.…”

“…29 Specifically, nitrosoureas like n-ethyl-n-nitrosourea (ENU) have been found to induce leukemia by alkylating nucleobases, disrupting DNA, and resulting in bone marrow suppression and the formation of leukemic cells. 30,31 ENU has also been observed to generate malignant cells in the brain and reproductive system in animal 4,32 Any disruption in the signaling cascade that regulates differentiation and proliferation can lead to hematological abnormalities, resulting in a buildup of cancerous cells in the bone marrow and blood.…”

“…ENU specifically is known to cause central nervous system (CNS) tumors and genetic disorders. 4 ENU administration in these models can help simulate and study tumor development, including leukemia. 5 Studies have shown that intravenous administration of ENU during pregnancy, at doses ranging from 40 to 80 mg/kg, increases the risk of CNS malignancies.…”