title: Hesperidin and Silibinin Ameliorate Aluminum-Induced Neurotoxicity: Modulation of Antioxidants and Inflammatory Cytokines Level in Mice Hippocampus.
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.
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India. ashokjangra123@gmail.com.
authors.forename: Ashok
authors.initials: A
authors.lastname: Jangra
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India.
authors.forename: Prajapati
authors.initials: P
authors.lastname: Kasbe
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India.
authors.forename: Surya Narayan
authors.initials: SN
authors.lastname: Pandey
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India.
authors.forename: Shubham
authors.initials: S
authors.lastname: Dwivedi
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India.
authors.forename: Satendra S
authors.initials: SS
authors.lastname: Gurjar
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India.
authors.forename: Mohit
authors.initials: M
authors.lastname: Kwatra
authors.affiliation: Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY, 40576, USA.
authors.forename: Murli
authors.initials: M
authors.lastname: Mishra
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India.
authors.forename: Athira K
authors.initials: AK
authors.lastname: Venu
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India.
authors.forename: Kunjbihari
authors.initials: K
authors.lastname: Sulakhiya
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India.
authors.forename: Ranadeep
authors.initials: R
authors.lastname: Gogoi
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India.
authors.forename: Nitul
authors.initials: N
authors.lastname: Sarma
authors.affiliation: Department of Pharmacology, Gauhati Medical College, Guwahati, Assam, 781032, India.
authors.forename: Babul K
authors.initials: BK
authors.lastname: Bezbaruah
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India. dr.lahkarniper@gmail.com.|Department of Pharmacology, Gauhati Medical College, Guwahati, Assam, 781032, India. dr.lahkarniper@gmail.com.
authors.forename: Mangala
authors.initials: M
authors.lastname: Lahkar
mesh_terms: D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy; D016207:Cytokines / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006569:Hesperidin / Q000737:chemistry*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000188:drug therapy; D009584:Nitrogen / Q000378:metabolism; D018384:Oxidative Stress; D000077385:Silybin; D012838:Silymarin / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D000077385:Silybin; D000535:Aluminum; D006569:Hesperidin; D002374:Catalase; D005978:Glutathione; D009584:Nitrogen
keywords: Aluminum chloride; Hesperidin; Neurotoxicity; Oxido-nitrosative stress; Proinflammatory cytokines; Silibinin