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All Trans Retinoic Acid Attenuates Markers of Neuroinflammation in Rat Brain by Modulation of SIRT1 and NFκB

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Abstract

Alcohol abuse affects several neurological pathways and causes significant alterations in the brain. Abstention from alcohol causes only a marginal decrease in oxidative stress and neuro inflammation. Our previous studies had shown that an active metabolite of vitamin A, all trans retinoic acid (ATRA), ameliorates alcohol induced toxicity. Hence in the present study we investigated whether ATRA regressed alcohol induced neuroinflammation. We focused on the role of silent mating type information regulation 2 homolog 1(SIRT1) and nuclear factor kappa-B (NFκB). Animals were administered with ethanol at a daily dose of (4 g/kg body weight) for 90 days. On the 91st day ethanol administration was stopped and animals were divided into ethanol abstention (A) and ATRA supplementation group (ATRA + A) (100 µg/kg body weight) and maintained for 30 days. Ethanol exposure increased markers of oxidative stress, inflammation and the activities of alcohol and acetaldehyde dehydrogenases and reduced the expression of SIRT1 in the whole brain.The ethanol induced altered expressions of NFκB and SIRT1 were modulated by supplementation of ATRA. Abstention also reduced toxicity, but to a lower extent in comparison with supplementation of ATRA. Our results seemed to suggest that ATRA regressed the mediators of ethanol induced neuroinflammation by reducing oxidative stress and by regulating the expression of NFκB and SIRT1. The ameliorative potential of ATRA was much higher than abstention.

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Acknowledgements

This work was supported by Kerala State Council for Science, Technology & Environment (vide order No. 974/2015/KSCSTE) and District Development Office for SC, Trivandrum (vide order No. B3-29455/16).

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  1. Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, 695 581, Kerala, India

    S. H. Priyanka, S. Syam Das, A. J. Thushara, Arun A. Rauf & M. Indira

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  1. S. H. Priyanka
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  2. S. Syam Das
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  3. A. J. Thushara
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Correspondence to M. Indira.

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Priyanka, S.H., Syam Das, S., Thushara, A.J. et al. All Trans Retinoic Acid Attenuates Markers of Neuroinflammation in Rat Brain by Modulation of SIRT1 and NFκB. Neurochem Res 43, 1791–1801 (2018). https://doi.org/10.1007/s11064-018-2595-7

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