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Effect of Alpha-Ketoglutarate on Neurobehavioral, Neurochemical and Oxidative Changes Caused by Sub-Chronic Cyanide Poisoning in Rats

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Abstract

Recent studies revealed that alpha-ketoglutarate (A-KG) alone or with sodium thiosulfate (STS) provide significant protection against acute and sub-acute cyanide poisoning in rodents. This study addresses the protective effect of A-KG and/or STS in sub-chronic (90 days) cyanide poisoning. Wistar rats were divided into seven groups (n = 10): Control animals, potassium cyanide (KCN) A-KG, STS, KCN + A-KG, KCN + STS and KCN + A-KG + STS. Spontaneous motor activity and motor coordination were recorded every 15th day. Lipid peroxidation (LPO), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in blood, brain, liver and kidney, and glutamate, aspartate and dopamine in discrete regions of brain were measured following 90 days exposure. Cyanide significantly decreased motor coordination, accompanied by increase in LPO (blood, brain and liver) and dopamine (corpus striatum and cerebral cortex) levels, and depletion in GSH (blood, brain and liver), GPx (brain and liver), SOD (brain and liver), and CAT (blood and brain) levels. Although treatment of A-KG and STS alone significantly blunted the toxicity of KCN, concomitant use of both afforded the maximum protection. This study shows a promising role of A-KG and STS as treatment regime for long term cyanide exposure.

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Acknowledgments

The authors acknowledge the financial support received from Defence Research and Development Establishment, Gwalior.

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Authors and Affiliations

  1. Department of Physiology, Chettinad Hospital & Research Institute, Kelambakkam, Tamil Nadu, 603 103, India

    D. C. Mathangi & R. Shyamala

  2. Department of Pathology, Chettinad Hospital & Research Institute, Kelambakkam, Tamil Nadu, 603 103, India

    R. Vijayashree & K. R. Rao

  3. Department of Pharmacology, Chettinad Hospital & Research Institute, Kelambakkam, Tamil Nadu, 603 103, India

    A. Ruckmani

  4. Defence Research and Development Establishment, Jhansi Road, Gwalior, Madhya Pradesh, 474 002, India

    R. Vijayaraghavan & R. Bhattacharya

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  1. D. C. Mathangi
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  4. K. R. Rao
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  7. R. Bhattacharya
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Correspondence to D. C. Mathangi.

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Mathangi, D.C., Shyamala, R., Vijayashree, R. et al. Effect of Alpha-Ketoglutarate on Neurobehavioral, Neurochemical and Oxidative Changes Caused by Sub-Chronic Cyanide Poisoning in Rats. Neurochem Res 36, 540–548 (2011). https://doi.org/10.1007/s11064-010-0376-z

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