N-acetylcysteine does not protect behavioral and biochemical toxicological effect after acute exposure of diphenyl ditelluride

作者：Comparsi Bruna; Meinerz Daiane F; Dalla Corte Cristiane L; Prestes Alessandro S; Stefanello Silvio T; Santos Danubia B; De Souza Diego; Farina Marcelo; Dafre Alcir L; Posser Thais; Franco Jeferson L; Rocha Joao B T^*

来源：Toxicology Mechanisms and Methods, 2014, 24(8): 529-535.

DOI：10.3109/15376516.2014.920449

• Glutathione peroxidase
• organotellurium compounds
• oxidative stress
• thioredoxin reductase
• toxicity

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 mu mol/kg, s.c.), (4) TFK i.p. plus (PhTe)(2) (50 mu mol/kg, s.c.), (5) NAC plus (PhTe)(2) (10 mu mol/kg, s.c.), and (6) NAC plus (PhTe)(2) (50 mu mol/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.

• 出版日期2014-12