title: Diphenyl Diselenide Protects Against Mortality, Locomotor Deficits and Oxidative Stress in Drosophila melanogaster Model of Manganese-Induced Neurotoxicity.
abstract: Several experimental and epidemiological reports have associated manganese exposure with induction of oxidative stress and locomotor dysfunctions. Diphenyl diselenide (DPDS) is widely reported to exhibit antioxidant, anti-inflammatory and neuroprotective effects in in vitro and in vivo studies via multiple biochemical mechanisms. The present study investigated the protective effect of DPDS on manganese-induced toxicity in Drosophila melanogaster. The flies were exposed, in a dietary regimen, to manganese alone (30 mmol per kg) or in combination with DPDS (10 and 20 µmol per kg) for 7 consecutive days. Exposure to manganese significantly (p < 0.05) increased flies mortality, whereas the survivors exhibited significant locomotor deficits with increased acetylcholinesterase (AChE) activity. However, dietary supplementation with DPDS caused a significant decrease in mortality, improvement in locomotor activity and restoration of AChE activity in manganese-exposed flies. Additionally, the significant decreases in the total thiol level, activities of catalase and glutathione-S-transferase were accompanied with significant increases in the generation of reactive oxygen and nitrogen species and thiobarbituric acid reactive substances in flies exposed to manganese alone. Dietary supplementation with DPDS significantly augmented the antioxidant status and prevented manganese-induced oxidative stress in the treated flies. Collectively, the present data highlight that DPDS may be a promising chemopreventive drug candidate against neurotoxicity resulting from acute manganese exposure.
authors.affiliation: Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria. dedac2001@yahoo.co.uk.
authors.forename: Isaac A
authors.initials: IA
authors.lastname: Adedara
authors.affiliation: Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: Amos O
authors.initials: AO
authors.lastname: Abolaji
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, CCNE, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil.
authors.forename: Joao B T
authors.initials: JB
authors.lastname: Rocha
authors.affiliation: Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: Ebenezer O
authors.initials: EO
authors.lastname: Farombi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001555:Benzene Derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004331:Drosophila melanogaster; D008345:Manganese / Q000633:toxicity*; D009026:Mortality / Q000639:trends; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control; D016566:Organoselenium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013606:Tabes Dorsalis / Q000378:metabolism* / Q000401:mortality / Q000517:prevention & control*
chemical_list: D001555:Benzene Derivatives; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; C061132:diphenyldiselenide; D008345:Manganese
keywords: Diphenyl diselenide (DPDS); Drosophila melanogaster; Manganese; Neurotoxicity; Oxidative stress