3.9 Article

Protective effects of novel organic selenium compounds against oxidative stress in the nematode Caenorhabditis elegans

Journal

TOXICOLOGY REPORTS
Volume 2, Issue -, Pages 961-967

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.toxrep.2015.06.010

Keywords

Caenorhabditis elegans; Diphenyl diselenide; Novel organic selenium compounds; GST-4::GFP; AChE; Juglone

Categories

Funding

  1. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPqUniversal) [472669/2011-7, 475896/2012-2]
  2. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
  3. Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul [11/2029-1]
  4. National Institute of Environmental Health Sciences (NIEHS) [R01 ES10563, R01 ES 07731]
  5. NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES007331, R01ES010563] Funding Source: NIH RePORTER

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Organic selenium compounds possess numerous biological properties, including antioxidant activity. Yet, the high toxicity of some of them, such as diphenyl diselenide (DPDS), is a limiting factor in their current usage. Accordingly, we tested four novel organic selenium compounds in the non-parasite nematode Caenorhabditis elegans and compared their efficacy to DPDS. The novel organic selenium compounds are beta-selenoamines 1-phenyl-3-(p-tolylselanyl)propan-2-amine (C1) and 1-(2-methoxyphenylselanyl)-3-phenylpropan-2-amine (C2) and analogs of DPDS 1,2-bis(2-methoxyphenyl)diselenide (C3) and 1,2-bisp-tolyldiselenide (C4). Synchronized worms at the L4 larval stage were exposed for one hour in M9 buffer to these compounds. Oxidative stress conditions were induced by juglone (200 mu M) and heat shock (35 degrees C). Moreover, we evaluated C. elegans behavior, GST-4::GFP (glutathione S-transferase) expression and the activity of acetylcholinesterase (AChE). All tested compounds efficiently restored viability in juglone stressed worms. However, DPDS, C2, C3 and C4 significantly decreased the defecation cycle time. Juglone-induced GST-4::GFP expression was not attenuated in worms pretreated with the novel compounds, except with C2. Finally, AChE activity was reduced by DPDS, C2, C3 and C4. To our knowledge, this is study firstly showed the effects of C1, C2, C3 and C4 selenium-derived compounds in C. elegans. Low toxic effects were noted, except for reduction in the defecation cycle, which is likely associated with AChE inhibition. The juglone-induced stress (reduced viability) was fully reversed by compounds to control animal levels. C2 was also efficient in reducing the juglone-induced GST-4::GFP expression, suggesting the latter may mediate the stress induced by this compound. Future studies could be profitably directed at addressing additional molecular mechanisms that mediate the protective effects of these novel organic selenium compounds. (C) 2015 Published by Elsevier Ireland Ltd.

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