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• W2022277230 endingPage "52" @default.
• W2022277230 startingPage "41" @default.
• W2022277230 abstract "Cytosine arabinoside (Ara-C), a pyrimidine analogue induces cerebellar dysfunction and behavioral abnormalities. Although many in vitro experiments have been conducted in the past demonstrating the lethal potential of Ara-C to cerebellar neurons, there is a paucity of literature available regarding the effects of Ara-C on the cellular and genetic material of cerebellum and its subsequent influence on the neurobehavioral performance in vivo. Rats were treated with Ara-C at the dose levels 50, 100 and 200 mg/kg/day for 5 and 14 days by intraperitoneal (i.p.) route. Endpoints of the evaluation included food and water intake, body and organ weight, behavioral parameters, histopathology, oxidative stress, DNA damage, apoptosis, expression of p53, caspase-3 and calbindin D-28K (calbindin) as well as histone acetylation and methylation. Ara-C treatment for 14 days significantly decreased the food and water intake, body weight gain and brain weight in rat as compared to the control. Alterations in various behavioral parameters were observed, indicating the impaired cerebellar function. Further, cellular abnormalities in the cerebellum such as Purkinje cell misalignment and granule cell cytotoxicity were observed. Positive correlation was observed between Ara-C induced disturbance in the motor performance and the Purkinje cell loss in rat cerebellum. Moreover, Ara-C treatment significantly increased the oxidative stress, DNA damage, TUNEL positive cells, p53 and caspase-3 positive cells in the rat cerebellum. Unlike short-term treatment, long-term Ara-C treatment significantly reduced calbindin expression in the cerebellum. Apart from this, 14 days Ara-C treatment led to significant alterations in the histone acetylation and methylation in the cerebellum, while in 5 days treatment no such alterations were observed. Present results indicated that Ara-C, by inducing oxidative stress mediated DNA damage, executes neuronal apoptosis which is accompanied by an increase in the p53 and caspase-3, but decrease in the calbindin expression." @default.
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• W2022277230 date "2012-03-01" @default.
• W2022277230 modified "2023-09-27" @default.
• W2022277230 title "Cytarabine induced cerebellar neuronal damage in juvenile rat: Correlating neurobehavioral performance with cellular and genetic alterations" @default.
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• W2022277230 doi "https://doi.org/10.1016/j.tox.2011.12.005" @default.
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