Effects of inorganic selenium administration in methylmercury‐induced neurotoxicity in mouse cerebral cortex

Abstract

Selenium can counteract methylmercury (MeHg) neurotoxicity. However, data about the neuroprotective effects of sodium selenite (Na(2)SeO(3)) on the activity of mitochondrial complexes and creatine kinase (mtCK) are scarce. Therefore, this study investigated the effects of the chronic exposure to Na(2)SeO(3) on brain energy metabolism and oxidative stress parameters in MeHg-poisoned mice. Adult male mice were orally treated with MeHg (40 mg L(-1) in drinking water, ad libitum) during 21 days and simultaneously administrated with daily subcutaneous injections of Na(2)SeO(3) (5 μmol kg(-1)), a potential neuroprotectant. Mitochondrial complexes I to IV and mtCK activities were measured in cerebral cortex mitochondria. The cerebro-cortical tissue was also used to evaluate the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR) activities, as well as lipid peroxidation. Metal deposition was followed autometalographically (AMG). Na(2)SeO(3) partially prevented MeHg-induced inhibition of complexes II-III, IV and mtCK activities; however, it was unable to prevent MeHg-induced complex I and II inhibition. MeHg increased lipid peroxidation, GR activity and decreased GPx activity in the cerebral cortex; however, Na(2)SeO(3) did not modify such events. Furthermore, Na(2)SeO(3)per se inhibited complexes I, II-III and IV and mtCK activities and increased GPx and GR activities and lipid peroxidation. These data show that inorganic selenium was ineffective in preventing most of the MeHg-induced brain biochemical alterations. However, the most prominent finding was the selenium-induced reduction of cells labelled for metal deposition. Although, the literature supports the beneficial effects of selenium against mercury toxicity, the toxic effects elicited by Na(2)SeO(3), alone or in combination with mercury, should be considered when this compound is proposed as a potential protective therapy for MeHg poisoning.

<i>S</i>-Mercuration of cellular proteins by methylmercury and its toxicological implications

“…In addition to this SOD-related research, it has been found in a number of studies that decreased GPx activity in the brains was caused by the mice being given MeHg at a concentration of 40 mg/L in drinking water for several weeks (Carvalho et al, 2007;Farina et al, 2003b;Franco et al, 2009;Glaser et al, 2010). Stringari et al (2008) reported that exposing pregnant mice to MeHg at concentrations of 1, 3, and 10 mg/L in drinking water induced a dose-dependent and long-lasting inhibitory effect on the occurrence of cerebral antioxidant enzymes, such as GPx, which is a developmental phenomenon, in their pups.…”

Cd, Pb and Hg Biomonitoring in Fish of the Mediterranean Region and Risk Estimations on Fish Consumption

“…Finally, we did not include in our analysis selenium, a metalloid of considerable interest for human health not only for its own nutritional and toxicological properties [77,78], but also for its ability to modify and generally decrease the biological activity of several heavy metals such as cadmium, lead and mercury. However, the relation of these metals with selenium is very complex and still not well elucidated [79,80], and paradoxically in some cases concurrent administration of selenium along with heavy metals may not mitigate the toxicity of the single elements, but even exacerbate it [77,[81][82][83], further hampering the risk assessment of mixed intake of these elements by seafood [84]. Overall, however, we consider it unlikely that lack of consideration of selenium in the present analysis may have substantially biased our results, though additional research is clearly required to adequately elucidate these potential inhibitory or additive interactions.…”

Collate the literature on toxicity data on mercury in experimental animals and humans (Part I – Data on organic mercury)

“…The activities of the respiratory chain mitochondrial complexes I-IV and the mitochondrial creatine kinase activity in cortical mitochondrial preparations were significantly reduced in treated animals. Metal deposits were evident in cortical cells (Glaser et al, 2010) Mercury toxicity in experimental animals and humans (2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011) Supporting publications 2012:EN-297 139…”