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Mitochondrial Oxidative Stress and Dysfunction in Rat Brain Induced by Carbofuran Exposure

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Abstract

Repeated low-dose exposure to carbofuran exerts its neurotoxic effects by non-cholinergic mechanisms. Emerging evidence indicates that oxidative stress plays an important role in carbofuran neurotoxicity after sub-chronic exposure. The purpose of the present study is to evaluate the role of mitochondrial oxidative stress and dysfunction as a primary event responsible for neurotoxic effects observed after sub-chronic carbofuran exposure. Carbofuran was administered to rats at a dose of 1 mg/kg orally for a period of 28 days. There was a significant inhibition in the activity of acetylcholinesterase (66.6%) in brain samples after 28 days of carbofuran exposure. Mitochondrial respiratory chain functions were assessed in terms of MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) reduction and activity of succinate dehydrogenase in isolated mitochondria. It was observed that carbofuran exposure significantly inhibited MTT reduction (31%) and succinate dehydrogenase activity (57%). This was accompanied by decrease in low-molecular weight thiols (66.6%) and total thiols (37.4%) and an increase in lipid peroxidation (43.7%) in the mitochondria isolated from carbofuran-exposed rat brain. The changes in mitochondrial oxidative stress and functions were associated with impaired cognitive and motor functions in the animals exposed to carbofuran as compared to the control animals. Based on these results, it is clear that carbofuran exerts its neurotoxicity by impairing mitochondrial functions leading to oxidative stress and neurobehavioral deficits.

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Authors and Affiliations

  1. Department of Biochemistry, Basic Medical Science Building, Panjab University, Chandigarh, 160014, India

    Sukhdev Singh Kamboj, Vikas Kumar, Amit Kamboj & Rajat Sandhir

  2. Department of Anatomy & Cell Biology, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS, 66160, USA

    Rajat Sandhir

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  1. Sukhdev Singh Kamboj
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  2. Vikas Kumar
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  3. Amit Kamboj
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  4. Rajat Sandhir
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Correspondence to Rajat Sandhir.

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Kamboj, S.S., Kumar, V., Kamboj, A. et al. Mitochondrial Oxidative Stress and Dysfunction in Rat Brain Induced by Carbofuran Exposure. Cell Mol Neurobiol 28, 961–969 (2008). https://doi.org/10.1007/s10571-008-9270-5

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  • DOI: https://doi.org/10.1007/s10571-008-9270-5

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