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

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2021 Sep 28

PMID 34577085

Authors

Maria Elena Camacho-Moll

Adriana Sampayo-Reyes

Fabiola Castorena-Torres

Gerardo Lozano-Garza

Gabriela Alarcon-Galvan

Alba Hernandez

Ricard Marcos

Juan Manuel Alcocer-Gonzalez

Reyes Tamez-Guerra

Mario Bermudez de Leon

Affiliations

Soon will be listed here.

Abstract

Arsenic is considered a worldwide pollutant that can be present in drinking water. Arsenic exposure is associated with various diseases, including cancer. Antioxidants as selenite and α-tocopherol-succinate have been shown to modulate arsenic toxic effects. Since changes in and gene expression have been associated with carcinogenesis, the aim of this study was to evaluate the effect of arsenic exposure and co-treatments with selenite or α-tocopherol-succinate on the expression of these genes, in the livers of chronically exposed Syrian golden hamsters. Animals were divided into six groups: (i) control, (ii) chronically treated with 100 ppm arsenic, (iii) treated with 6 ppm α-tocopherol-succinate (α-TOS), (iv) treated with 8.5 ppm selenite, (v) treated with arsenic + α-TOS, and (vi) treated with arsenic + selenite. Urine samples and livers were collected after 20 weeks of continuous exposure. The urine samples were analyzed for arsenic species by atomic absorption spectrophotometry, and real-time RT-qPCR analysis was performed for gene expression evaluation. A reduction in expression was observed in the selenite-treated group. No differences in expression were found among groups. Histopathological analysis revealed hepatic lymphocytosis in selenite-treated animals. As a conclusion, long-term exposure to arsenic does not significantly alter the expression of and oncogenes in the livers of hamsters; however, selenite down-regulates expression and provokes lymphocytosis.

References

Matsushita M, Freigang S, Schneider C, Conrad M, Bornkamm G, Kopf M . T cell lipid peroxidation induces ferroptosis and prevents immunity to infection. J Exp Med. 2015; 212(4):555-68. PMC: 4387287. DOI: 10.1084/jem.20140857. View

Higashitsuji H, Liu Y, Mayer R, Fujita J . The oncoprotein gankyrin negatively regulates both p53 and RB by enhancing proteasomal degradation. Cell Cycle. 2005; 4(10):1335-7. DOI: 10.4161/cc.4.10.2107. View

Drobna Z, Styblo M, Thomas D . An Overview of Arsenic Metabolism and Toxicity. Curr Protoc Toxicol. 2014; 42(431):4.31.1-4.31.6. PMC: 4240622. DOI: 10.1002/0471140856.tx0431s42. View

ENTERLINE P, Day R, Marsh G . Cancers related to exposure to arsenic at a copper smelter. Occup Environ Med. 1995; 52(1):28-32. PMC: 1128146. DOI: 10.1136/oem.52.1.28. View

Del Razo L, Garcia-Vargas G, Valenzuela O, Castellanos E, Sanchez-Pena L, Currier J . Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: a cross-sectional study in the Zimapán and Lagunera regions in Mexico. Environ Health. 2011; 10:73. PMC: 3169452. DOI: 10.1186/1476-069X-10-73. View

Elshenawy O, Abdelhamid G, Soshilov A, Denison M, El-Kadi A . Down-regulation of cytochrome P450 1A1 by monomethylarsonous acid in human HepG2 cells. Toxicol Lett. 2017; 270:34-50. DOI: 10.1016/j.toxlet.2017.02.012. View

Wang Z, Li J, Xiao W, Long J, Zhang H . The STAT3 inhibitor S3I-201 suppresses fibrogenesis and angiogenesis in liver fibrosis. Lab Invest. 2018; 98(12):1600-1613. DOI: 10.1038/s41374-018-0127-3. View

Benko I, Nagy G, Tanczos B, Ungvari E, Sztrik A, Eszenyi P . Subacute toxicity of nano-selenium compared to other selenium species in mice. Environ Toxicol Chem. 2012; 31(12):2812-20. DOI: 10.1002/etc.1995. View

Kane A, Deenick E, Ma C, Cook M, Uzel G, Tangye S . STAT3 is a central regulator of lymphocyte differentiation and function. Curr Opin Immunol. 2014; 28:49-57. DOI: 10.1016/j.coi.2014.01.015. View

10.

Ren Z, Fan Y, Zhang Z, Chen C, Chen C, Wang X . Sodium selenite inhibits deoxynivalenol-induced injury in GPX1-knockdown porcine splenic lymphocytes in culture. Sci Rep. 2018; 8(1):17676. PMC: 6281670. DOI: 10.1038/s41598-018-36149-x. View

11.

Tsuji P, Carlson B, Anderson C, Seifried H, Hatfield D, Howard M . Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice. Nutrients. 2015; 7(8):6529-49. PMC: 4555136. DOI: 10.3390/nu7085297. View

12.

Chi L, Bian X, Gao B, Ru H, Tu P, Lu K . Sex-Specific Effects of Arsenic Exposure on the Trajectory and Function of the Gut Microbiome. Chem Res Toxicol. 2016; 29(6):949-51. PMC: 5079644. DOI: 10.1021/acs.chemrestox.6b00066. View

13.

Li S, Ding Y, Niu Q, Xu S, Pang L, Ma R . Lutein has a protective effect on hepatotoxicity induced by arsenic via Nrf2 signaling. Biomed Res Int. 2015; 2015:315205. PMC: 4357133. DOI: 10.1155/2015/315205. View

14.

Dong L, Yang G, Pan Y, Chen Y, Tan Y, Dai R . The oncoprotein p28GANK establishes a positive feedback loop in β-catenin signaling. Cell Res. 2011; 21(8):1248-61. PMC: 3193485. DOI: 10.1038/cr.2011.103. View

15.

Bailey K, Wu M, Ward W, Smeester L, Rager J, Garcia-Vargas G . Arsenic and the epigenome: interindividual differences in arsenic metabolism related to distinct patterns of DNA methylation. J Biochem Mol Toxicol. 2013; 27(2):106-15. PMC: 3892431. DOI: 10.1002/jbt.21462. View

16.

Hoffmann F, Hashimoto A, Shafer L, Dow S, Berry M, Hoffmann P . Dietary selenium modulates activation and differentiation of CD4+ T cells in mice through a mechanism involving cellular free thiols. J Nutr. 2010; 140(6):1155-61. PMC: 2869499. DOI: 10.3945/jn.109.120725. View

17.

Di Napoli M, Maresca V, Sorbo S, Varcamonti M, Basile A, Zanfardino A . Proteins of the fruit pulp of have antimicrobial activity directed against the bacterial membranes. Nat Prod Res. 2019; 35(17):2942-2946. DOI: 10.1080/14786419.2019.1675655. View

18.

Khairul I, Wang Q, Jiang Y, Wang C, Naranmandura H . Metabolism, toxicity and anticancer activities of arsenic compounds. Oncotarget. 2017; 8(14):23905-23926. PMC: 5410354. DOI: 10.18632/oncotarget.14733. View

19.

Sun H, Rathinasabapathi B, Wu B, Luo J, Pu L, Ma L . Arsenic and selenium toxicity and their interactive effects in humans. Environ Int. 2014; 69:148-58. DOI: 10.1016/j.envint.2014.04.019. View

20.

Browning L, Patel M, Horvath E, Tawara K, Jorcyk C . IL-6 and ovarian cancer: inflammatory cytokines in promotion of metastasis. Cancer Manag Res. 2018; 10:6685-6693. PMC: 6287645. DOI: 10.2147/CMAR.S179189. View