title: Effectiveness of γ-oryzanol in reducing neuromotor deficits, dopamine depletion and oxidative stress in a Drosophila melanogaster model of Parkinson's disease induced by rotenone.
abstract: The γ-orizanol present in rice bran oil contains a mix of steryl triterpenyl esters of ferulic acid, which is believed to be linked to its antioxidant potential. In this study we investigated the neuroprotective actions of γ-orizanol (ORY) against the toxicity induced by rotenone (ROT) in Drosophila melanogaster. The flies (both genders) aged between 1 and 5 days old were divided into four groups of 50 flies each: (1) control, (2) ORY 25 μM, (3) ROT 500 μM, (4) ORY 25 μM+ROT 500 μM. Flies were concomitantly exposed to a diet containing ROT and ORY for 7 days according to their respective groups. Survival and behavior analyses were carried out in vivo, and ex vivo analyses involved acetylcholinesterase activity (AChE), determination of dopaminergic levels, cellular viability and mitochondrial viability, activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reactive species levels (RS), lipid peroxidation (TBARS) and contents of total thiols and non-proteic thiols (NPSH). Our results show for the first time that ORY not only acts as an endogenous activator of the cellular antioxidant defenses, but it also ameliorates rotenone induced mortality, oxidative stress and mitochondrial dysfunction. Our salient findings regarded the restoration of cholinergic deficits, dopamine levels and improved motor function provided by ORY. These results demonstrate the neuroprotective potential of ORY and that this effect can be potentially due to its antioxidant action. In conclusion, the present results show that ORY is effective in reducing the ROT induced toxicity in D. melanogaster, which showed a neuroprotective action, possibly due to the presence of the antioxidant constituents such as the ferulic acid.
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, Itaqui CEP 97650-000, RS, Brazil.
authors.forename: Stífani Machado
authors.initials: SM
authors.lastname: Araujo
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, Itaqui CEP 97650-000, RS, Brazil.
authors.forename: Mariane Trindade
authors.initials: MT
authors.lastname: de Paula
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, Itaqui CEP 97650-000, RS, Brazil.
authors.forename: Marcia Rósula
authors.initials: MR
authors.lastname: Poetini
authors.affiliation: Department of Nutrition, UNIPAMPA, Campus Itaqui, RS, Brazil.
authors.forename: Luana
authors.initials: L
authors.lastname: Meichtry
authors.affiliation: Department of Nutrition, UNIPAMPA, Campus Itaqui, RS, Brazil.
authors.forename: Vandreza Cardoso
authors.initials: VC
authors.lastname: Bortolotto
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, Itaqui CEP 97650-000, RS, Brazil.
authors.forename: Micheli Stefani
authors.initials: MS
authors.lastname: Zarzecki
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, Itaqui CEP 97650-000, RS, Brazil; Department of Nutrition, UNIPAMPA, Campus Itaqui, RS, Brazil.
authors.forename: Cristiano Ricardo
authors.initials: CR
authors.lastname: Jesse
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, Itaqui CEP 97650-000, RS, Brazil; Department of Nutrition, UNIPAMPA, Campus Itaqui, RS, Brazil. Electronic address: marinaprigol@gmail.com.
authors.forename: Marina
authors.initials: M
authors.lastname: Prigol
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004331:Drosophila melanogaster; D005260:Female; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D010666:Phenylpropionates / Q000008:administration & dosage*; D012402:Rotenone / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D007306:Insecticides; D010666:Phenylpropionates; D012402:Rotenone; D000110:Acetylcholinesterase; C013172:gamma-oryzanol; D004298:Dopamine
keywords: Dopamine; Drosophila melanogaster; Neurotoxicty; Oxidative stress; Rotenone; γ-Oryzanol