title: Neuroprotective effects of various doses of topiramate against methylphenidate induced oxidative stress and inflammation in rat isolated hippocampus.
abstract: Methylphenidate (MPH) abuse causes neurodegeneration. The neuroprotective effects of topiramate (TPM) have been reported but its putative mechanism remains unclear. The current study evaluates the role of various doses of TPM on protection of rat hippocampal cells from MPH-induced oxidative stress and inflammation in vivo. Seventy adult male rats were divided into six groups. Group 1 received normal saline (0.7 mL/rat) and group 2 was injected with MPH (10 mg/kg) for 21 days. Groups 3, 4, 5, 6 and 7 concurrently were treated by MPH (10 mg/kg) and TPM (10, 30, 50, 70 and 100 mg/kg, intraperitoneally (i.p.)), respectively for 21 days. After drug administration, the open field test (OFT) was used to investigate motor activity. Oxidative, antioxidant and inflammatory factors were measured in isolated hippocampus. Also, the brain-derived neurotrophic factor (BDNF) level was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. Cresyl violet staining of Dentate Gyrus (DG) and CA1 cell layers of the hippocampus were also performed. MPH significantly disturbs motor activity in OFT and TPM (70 and 100 mg/kg) decreased this disturbance. Also MPH significantly increased lipid peroxidation, mitochondrial reduced state of glutathione (GSH) level, interleukin (IL)-1β and tumour necrosis factor (TNF)-α and BDNF level in isolated hippocampal cells. Also superoxide dismutase, glutathione peroxidase and glutathione reductase activity significantly decreased. Various doses of TPM attenuated these effects and significantly decreased MPH-induced oxidative damage, inflammation and hippocampal cell loss and increased BDNF level. This study suggests that TPM has the potential to be used as a neuroprotective agent against oxidative stress and neuroinflammation induced by frequent use of MPH.
authors.affiliation: Razi Drug Research Centre and Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Motaghinejad
authors.affiliation: Razi Drug Research Centre and Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Manijeh
authors.initials: M
authors.lastname: Motevalian
authors.affiliation: Solid Dosage Form Department, Iran Hormone Pharmaceutical Company, Tehran, Iran.
authors.forename: Behnaz
authors.initials: B
authors.lastname: Shabab
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008774:Methylphenidate / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D000077236:Topiramate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D000077236:Topiramate; D008774:Methylphenidate; D005632:Fructose; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione; D019803:Glutathione Disulfide
keywords: BDNF; inflammation; methylphenidate; oxidative stress; topiramate