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Hesperidin and Silibinin Ameliorate Aluminum-Induced Neurotoxicity: Modulation of Antioxidants and Inflammatory Cytokines Level in Mice Hippocampus

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Abstract

Mounting evidence suggests that long-term aluminum exposure results in severe toxic effects, including neurobehavioral and neurochemical anomalies. The present study was performed to examine the neuroprotective potential of hesperidin and silibinin against aluminum chloride (AlCl3)-induced neurotoxicity in mice. AlCl3 (100 mg/kg/day) was injected daily through oral gavage for 42 days. Concomitantly, hesperidin (50 and 100 mg/kg/day, p.o.) and silibinin (100 and 200 mg/kg/day, p.o.) was administered for 42 days in different groups. The extent of cognitive impairment was assessed by Morris water maze and novel object recognition test on the 43rd day. Neurotoxicity was assessed by measuring oxido-nitrosative stress and proinflammatory cytokines in the hippocampus of mice. Six weeks treatment with AlCl3 caused cognitive impairment as indicated by an increase in the retention latency time and reduction in the percentage of recognition index. AlCl3-treated group showed oxido-nitrosative stress as indicated by increase in the level of lipid peroxidation, nitrite and depleted reduced glutathione, catalase activity in the hippocampus. Moreover, the chronic AlCl3 administration raised the proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α) level and increased acetylcholinesterase activity and reduced the BDNF content in the hippocampus of AlCl3-treated animals. However, chronic treatment with hesperidin and silibinin at higher doses significantly ameliorated the AlCl3-induced cognitive impairment and hippocampal biochemical anomalies. The present study clearly indicated that hesperidin and silibinin exert neuroprotective effects against AlCl3-induced cognitive impairment and neurochemical changes. Amelioration of cognitive impairment may be attributed to the impediment of oxido-nitrosative stress and inflammation in the hippocampus.

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Acknowledgments

We would like to thank the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India, for financial support. The authors are immensely thankful to the Institutional Level Biotech hub, NIPER Guwahati for providing technical support.

Conflict of Interest

The authors declare no financial or commercial conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India

    Ashok Jangra, Prajapati Kasbe, Surya Narayan Pandey, Shubham Dwivedi, Mohit Kwatra, Athira K. Venu, Kunjbihari Sulakhiya, Nitul Sarma & Mangala Lahkar

  2. Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India

    Satendra S. Gurjar & Ranadeep Gogoi

  3. Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY, 40576, USA

    Murli Mishra

  4. Department of Pharmacology, Gauhati Medical College, Guwahati, Assam, 781032, India

    Babul K. Bezbaruah & Mangala Lahkar

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  1. Ashok Jangra
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Correspondence to Mangala Lahkar.

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Jangra, A., Kasbe, P., Pandey, S.N. et al. Hesperidin and Silibinin Ameliorate Aluminum-Induced Neurotoxicity: Modulation of Antioxidants and Inflammatory Cytokines Level in Mice Hippocampus. Biol Trace Elem Res 168, 462–471 (2015). https://doi.org/10.1007/s12011-015-0375-7

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