title: N-Acetylcysteine does not protect behavioral and biochemical toxicological effect after acute exposure of diphenyl ditelluride.
abstract: Diphenyl ditelluride (PhTe)₂ is a versatile molecule used in the organic synthesis and it is a potential prototype for the development of novel biologically active molecules. The mechanism(s) involved in (PhTe)₂ toxicity is(are) elusive, but thiol oxidation of critical proteins are important targets. Consequently, the possible remedy of its toxicity by thiol-containing compounds is of experimental and clinical interest. The present study aimed to investigate putative mechanisms underlying the toxicity of (PhTe)₂ in vivo. We assessed behavioral and oxidative stress parameters in mice, including the modulation of antioxidant enzymatic defense systems. In order to mitigate such toxicity, N-acetylcysteine (NAC) was administered before (3 d) and simultaneously with (PhTe)₂ (7 d). Mice were separated into six groups receiving daily injections of (1) TFK (2.5 ml/kg, intraperitonealy (i.p.)) plus canola oil (10 ml/kg, subcutaneously (s.c.)), (2) NAC (100 mg/kg, i.p.) plus canola oil s.c., (3) TFK i.p. plus (PhTe)₂ (10 µmol/kg, s.c.), (4) TFK i.p. plus (PhTe)₂ (50 µmol/kg, s.c.), (5) NAC plus (PhTe)₂ (10 µmol/kg, s.c.), and (6) NAC plus (PhTe)₂ (50 µmol/kg, s.c.). (PhTe)₂ treatment started on the fourth day of treatment with NAC. Results demonstrated that (PhTe)₂ induced behavioral alterations and inhibited important selenoenzymes (thioredoxin reductase and glutathione peroxidase). Treatments produced no or minor effects on the activities of antioxidant enzymes catalase and glutathione reductase. Contrary to expected, NAC co-administration did not protect against the deleterious effects of (PhTe)₂. Other low-molecular-thiol containing molecules should be investigated to determine whether or not they can be effective against ditellurides.
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria , Santa Maria, RS , Brazil .
authors.forename: Bruna
authors.initials: B
authors.lastname: Comparsi
authors.forename: Daiane F
authors.initials: DF
authors.lastname: Meinerz
authors.forename: Cristiane L
authors.initials: CL
authors.lastname: Dalla Corte
authors.forename: Alessandro S
authors.initials: AS
authors.lastname: Prestes
authors.forename: Sílvio T
authors.initials: ST
authors.lastname: Stefanello
authors.forename: Danúbia B
authors.initials: DB
authors.lastname: Santos
authors.forename: Diego
authors.initials: D
authors.lastname: De Souza
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.forename: Alcir L
authors.initials: AL
authors.lastname: Dafre
authors.forename: Thaís
authors.initials: T
authors.lastname: Posser
authors.forename: Jeferson L
authors.initials: JL
authors.lastname: Franco
authors.forename: João B T
authors.initials: JB
authors.lastname: Rocha
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D001555:Benzene Derivatives / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D020258:Neurotoxicity Syndromes / Q000201:enzymology* / Q000517:prevention & control; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023382:Toxicity Tests, Acute
chemical_list: D000975:Antioxidants; D001555:Benzene Derivatives; D004785:Environmental Pollutants; D009419:Nerve Tissue Proteins; D009942:Organometallic Compounds; C434247:diphenylditelluride; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase; D000111:Acetylcysteine
keywords: Glutathione peroxidase; organotellurium compounds; oxidative stress; thioredoxin reductase; toxicity