Selenite restores Pax6 expression in neuronal cells of chronically arsenic-exposed Golden Syrian hamsters

Abstract

Arsenic is a worldwide environmental pollutant that generates public health concerns. Various types of cancers and other diseases, including neurological disorders, have been associated with human consumption of arsenic in drinking water. At the molecular level, arsenic and its metabolites have the capacity to provoke genome instability, causing altered expression of genes. One such target of arsenic is the Pax6 gene that encodes a transcription factor in neuronal cells. The aim of this study was to evaluate the effect of two antioxidants, α-tocopheryl succinate (α-TOS) and sodium selenite, on Pax6 gene expression levels in the forebrain and cerebellum of Golden Syrian hamsters chronically exposed to arsenic in drinking water. Animals were divided into six groups. Using quantitative real-time reverse transcriptase (RT)-PCR analysis, we confirmed that arsenic downregulates Pax6 expression in nervous tissues by 53 ± 21% and 32 ± 7% in the forebrain and cerebellum, respectively. In the presence of arsenic, treatment with α-TOS did not modify Pax6 expression in nervous tissues; however, sodium selenite completely restored Pax6 expression in the arsenic-exposed hamster forebrain, but not the cerebellum. Although our results suggest the use of selenite to restore the expression of a neuronal gene in arsenic-exposed animals, its use and efficacy in the human population require further studies.

Selenite Downregulates STAT3 Expression and Provokes Lymphocytosis in the Liver of Chronically Exposed Syrian Golden Hamsters

“…Hamsters in each group were monitored every week for 20 weeks to evaluate weight gain and survival, in animals exposed chronically to arsenic and/or the selected antioxidants (selenite and α-tocopherol). Arsenic dose was chosen based in our previous studies [ 14 , 21 ], where it resembles the arsenic toxicity effect observed in human population [ 8 ]. For α-TOS and selenite doses, they were chosen on previous studies in animal models where not toxicity was observed by these two antioxidants [ 14 , 21 , 27 , 28 ].…”

“…Arsenic dose was chosen based in our previous studies [ 14 , 21 ], where it resembles the arsenic toxicity effect observed in human population [ 8 ]. For α-TOS and selenite doses, they were chosen on previous studies in animal models where not toxicity was observed by these two antioxidants [ 14 , 21 , 27 , 28 ]. No difference in weight gain was found among treatments, except in selenite-treated hamsters at 10 weeks compared to the control group ( p < 0.05, Figure 1 A).…”

“…In Mexico and other regions in the world, there are areas where the human population is environmentally exposed to arsenic in drinking water, and some studies have reported association of this chronic exposure and diseases [ 7 , 15 , 29 , 30 ]. Therefore, the present study aimed to determine whether arsenic toxicity could be modulated by selenite and α- tocopherol, two antioxidants which have been shown to ameliorate arsenic toxic effects [ 21 , 31 , 32 ], and we used to oncogenic markers, i.e., STAT3 and PSMD10 genes, and an histological approach to reveal the grade of liver alteration.…”

“…Doses for the administered compounds are listed in Table 1 . The sodium arsenite dose was based on previous studies [ 21 , 58 ], and the doses of α-tocopherol succinate (α-TOS) and sodium selenite were chosen based on studies showing no toxicity in animals [ 14 , 21 , 27 , 28 ]. Before euthanasia, animals were housed in metabolic cages.…”

“…Recently it has been shown that the oncogene 26S Proteasome non-ATPase regulatory subunit 10 ( PSMD10 ) induces STAT3 activation in a tumor microenvironment [ 16 ]. Although arsenic can modify the expression of several genes [ 21 , 22 ], and some oncogenes such as STAT3 and PSMD10 have been associated with malignant transformation of hepatocytes [ 23 , 24 , 25 , 26 ], our knowledge of arsenic’s targets and effects on cancer etiology are unclear. Evidence has been accumulating in recent years about the important role that PSMD10 plays in hepatocellular carcinoma, for instance it has been shown to prevent the degradation of Octamer-binding transcription factor 4 (Oct4), regulates Retinoblastoma 1 (Rb1), tumor protein 53 (Tp53) and cisplatin sensitivity.…”