title: Trolox ameliorates 3-nitropropionic acid-induced neurotoxicity in rats.
abstract: 3-nitropropionic acid (3-NPA) is a naturally occurring neurotoxin produced by legumes of the genus Astragalus and Arthrium fungi. Acute exposure to 3-NPA results in striatal astrocytic death and variety of behavior dysfunction in rats. Oxidative stress has been reported to play an important role in 3-NPA-induced neurotoxicity. Trolox is a potent free radical chain breaking antioxidant which has been shown to restore structure and function of the nervous system following oxidative stress. This rapid and efficient antioxidant property of trolox was attributed to its enhanced water solubility as compared with alpha-tocopherol. This investigation was aimed to study the effect of trolox against 3-NPA-induced neurotoxicity in female Wistar rats. The animals received trolox (0, 40 mg, 80 mg and 160 mg/kg, orally) daily for 7 days. 3-NPA (25mg/kg, i.p.) was administered daily 30 min after trolox for the same duration. One additional group of rats served as control (vehicle only). On day 8, the animals were observed for neurobehavioral performance. Immediately after behavioral studies, the animal's brains were dissected out for histological studies. Lesions in the striatal dopaminergic neurons were assessed by immunohistochemical method using tyrosine hydroxylase immunostaining. Administration of 3-NPA alone caused significant depletion of striatal dopamine and glutathione, whereas, the levels of thiobarbituric acid reactive substance (TBARS) and nitric oxide (NO) were significantly increased suggesting an elevated level of oxidative stress. Trolox significantly and dose-dependently protected animals against 3-NPA-induced neurobehavioral, neurochemical and structural abnormalities. These results clearly suggest that protective effect of trolox against 3-NPA-induced neurotoxicity is mediated through its free radical scavenging activity.
authors.affiliation: Department of Biochemistry, College of Medicine, King Faisal University, Dammam, Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al Mutairy
authors.forename: Saeed
authors.initials: S
authors.lastname: Al Kadasah
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Elfaki
authors.forename: Mohammed
authors.initials: M
authors.lastname: Arshaduddin
authors.forename: Dilshad
authors.initials: D
authors.lastname: Malik
authors.forename: Khalaf
authors.initials: K
authors.lastname: Al Moutaery
authors.forename: Mohammad
authors.initials: M
authors.lastname: Tariq
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005978:Glutathione / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism; D009574:Nitro Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011422:Propionates / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016896:Treatment Outcome; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002839:Chromans; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D014446:Tyrosine 3-Monooxygenase; D005978:Glutathione; C015392:3-nitropropionic acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D004298:Dopamine