Toxicological Study of Sodium Selenite on Fetal Development and DNA Fragmentation in Liver Cells of Pregnant Rats
Abstract
The present study was carried out to evaluate the effects of sodium selenite on fetal development and DNA in liver of rats. Pregnant rats were divided into three groups: control group, group treated orally with 5 µg Se/kg body wt. and group treated orally with 10 µg Se/kg body wt. Dams were treated orally with sodium selenite from day 7 to 19 of gestation. Sodium selenite treatment revealed decrease in maternal body weight, reduction in fetal weight, length and number of viable fetuses, increased number of resorbed fetuses and post-implantation loss at the two doses tested. Fetal skeleton showed signs of developmental delay in skull and limbs of the treated groups. Sodium selenite treatment revealed significant reduction of placental and liver weights in treated dams. Sodium selenite-induced oxidative stress in liver tissue of rats as evidenced by increase in lipid peroxidation and glutathione peroxidase activity, while catalase was significantly decreased. Also, increase in DNA fragmentation, marked reduction of hepatic DNA content, and many histopathological changes in the liver were recorded. The results demonstrated that treatment of pregnant rats with sodium selenite at the toxic dosages chosen showed maternal and fetal toxicity that may be concerned with hepatic oxidative stress accompanied with DNA fragmentation and depletion of total DNA content.
Keywords
Sodium selenite Maternal toxicity Fetal development Lipid peroxidation DNA fragmentation LiverReferences
- 1.Ward MA, Neville TL, Reed JJ, Taylor JB, Hallford DM, Soto-Navarro SA, Vonnahme KA, Redmer DS, Reynolds LP, Caton JS (2008) Effects of selenium supply and dietary restriction on maternal and fetal metabolic hormones in pregnant ewe lambs. J Anim Sci 86:1254–1262PubMedCrossRefGoogle Scholar
- 2.Spallholz JE (1994) On the nature of selenium toxicity and carcinostatic activity. Free Radic Biol Med 17(1):45–64PubMedCrossRefGoogle Scholar
- 3.Usami M, Tabata H, Ohno Y (1999) Effects of ascorbic acid on selenium teratogenicity in cultured rat embryos. Toxicol Lett 105:123–128PubMedCrossRefGoogle Scholar
- 4.Teh SJ, Deng X, Teh FC, Hung SO (2002) Selenium-induced teratogenicity in Sacramento splittail (Pogonichthys macrolepidotus). Mar Environ Res 54:605–608PubMedCrossRefGoogle Scholar
- 5.Papp LV (2007) From selenium to selenoproteins: synthesis, identity, and their role in human health. Antioxid Redox Signal 9:75–806Google Scholar
- 6.Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590PubMedCrossRefGoogle Scholar
- 7.Kim IY, Kim TS, Chung YW, Jeong D (2007) Selenium-induced apoptosis. Selenium. 2nd Edition. Part III pp 379–385. Its Molecular Biology and Role in Human Health. Springer US. doi: 10.1007/0-387-33827-6. ISBN: 978-0-387-33826-2 (Print) 978-0-387-33827-9 (Online)
- 8.Hays AW (2001) Principles and methods of toxicology. In: Christian MS (ed) Test methods for assessing female reproductive and developmental toxicology (Embryogenesis), Chapter 29, 4th edn. Taylor and Francis, USA, pp 1301–1317Google Scholar
- 9.Pletnikova IP (1970) Biological effect and safe concentration of selenium in drinking water. Hyg Sanit 35:176–180Google Scholar
- 10.Cummins LM, Kimura ET (1971) Safety evaluation of selenium sulfiide antidandruff shampoos. Toxicol Appl Pharmacol 20:89–96PubMedCrossRefGoogle Scholar
- 11.McLeod MJ (1980) Differential staining of cartilage and bone in whole mouse fetuses by Alcian blue and Alizarin red. Teratology 22:299–301PubMedCrossRefGoogle Scholar
- 12.Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70(1):158–169PubMedGoogle Scholar
- 13.Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126PubMedCrossRefGoogle Scholar
- 14.Ohkawa N, Ohishi W, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358PubMedCrossRefGoogle Scholar
- 15.Raisbeck MF, Dahl ER, Sanchez EL, Belden D (1993) Naturally occurring selenosis in Wyoming. J Vet Diagn Invest 5:84–87PubMedGoogle Scholar
- 16.Willhite CC (1993) Selenium teratogenesis: species-dependent response and influence on reproduction. Ann N Y Acad Sci 678:169–177PubMedCrossRefGoogle Scholar
- 17.Puls R (1994) Selenium. In: Mineral levels in animal health. Sherpa International, Clearbrook, BC, Canada, pp 230–234Google Scholar
- 18.Beems RB, Van Beek L (1985) Short-term (6-week) oral toxicity study of selenium in Syrian hamsters. Food Chem Toxicol 23:945–947PubMedCrossRefGoogle Scholar
- 19.Opresko DM (1993) Toxicity summary for selenium and selenium compounds, biomedical and environmental information analysis section, health and safety research division. Oak Ridge National Laboratory, Oak RidgeGoogle Scholar
- 20.Usami M, Tabata H, Ohno Y (2002) Effects of methionine on selenium embryotoxicity in cultured rat embryos. Teratog Carcinog Mutagen 22(4):301–308PubMedCrossRefGoogle Scholar
- 21.Favero AM, Weis SN, Stangherlin EC, Zeni G, Rocha JB, Nogueira CW (2005) Teratogenic effects of diphenyl diselenide in Wistar rats. Reprod Toxicol 20:561–568PubMedCrossRefGoogle Scholar
- 22.Weisa SN, Faveroa AM, Stangherlina EC, Manarina FG, Rochaa JB, Nogueiraa CW, Zeni G (2007) Repeated administration of diphenyl diselenide to pregnant rats induces adverse effects on embryonic/fetal development. Reprod Toxicol 23:175–181CrossRefGoogle Scholar
- 23.Yang G, Yin S, Zhou R, Gu L, Yan B, Liu Y, Liu Y (1989) Studies of safe maximal daily dietary Se-intake in a seleniferous area in China. J Trace Elem Electrolytes Health Dis 3(2):123–130PubMedGoogle Scholar
- 24.Shariff MA, Krishnamurti CR, Schaefer AL, Heindze AM (1984) Bidirectional transfer of selenium across the sheep placenta in utero. Can J Ann Sci 64:252–254CrossRefGoogle Scholar
- 25.Bedwal RS, Bahuguna A (1994) Zinc, copper and selenium in reproduction. Experientia 50:626–640PubMedCrossRefGoogle Scholar
- 26.Yaeger MJ, Neiger RD, Holler L, Fraser TL, Hurley DJ, Palmer IS (1998) The effect of sub clinical selenium toxicosis on pregnant beef cattle. J Vet Diagn Invest 10:268–273PubMedGoogle Scholar
- 27.Usami M, Tabata H, Ohno Y (1999) Effects of glutathione depletion on selenite- and selenate-induced embryotoxicity in cultured rat embryos. Teratog Carcinog Mutagen 19(4):257–266PubMedCrossRefGoogle Scholar
- 28.Hafeman DG, Sunde RA, Hoekstra WG (1973) Effect of dietary selenium on erythrocyte and liver glutathione peroxidase in the rat. Fed Proc 32:885 (abstr.)Google Scholar
- 29.Li L, Xie Y, El-Sayed WM, Szakacs JG, Roberts JC (2004) Characteristics of selenazolidine prodrugs of selenocysteine: toxicity, selenium levels, and glutathione peroxidase induction in A/J mice. Life Sci 75:447–459PubMedCrossRefGoogle Scholar
- 30.Hoffman DJ (2002) Role of selenium toxicity and oxidative stress in aquatic birds. Aquat Toxicol J 57(1):11CrossRefGoogle Scholar
- 31.Zhang J, Wang H, Yan X, Zhang L (2005) Comparison of short-term toxicity between Nano-Se and selenite in mice. Life Sci 76(10):1099–1109PubMedCrossRefGoogle Scholar
- 32.Lane HW, Strength R, Johnson J (1991) Effect of chemical form of selenium on tissue glutathione peroxidase activity in developing rats. J Nutr 121:80–86PubMedGoogle Scholar
- 33.Zhang Z, Tian Y, Yang X, Xia Y (1998) Effect of dietary selenium on the activities of glutathione peroxidase and deiodinase in rat liver. Wei Sheng Yan Jiu 27(3):209–211PubMedGoogle Scholar
- 34.Zhang JS, Gao XY, Zhang LD, Bao YP (2001) Biological effects of a nano red elemental selenium. BioFactors 15(1):27–38PubMedCrossRefGoogle Scholar
- 35.Spallholz JE (1997) Free radical generation by selenium compounds and their prooxidant toxicity. Biomed Environ Sci 10(2-3):260–270PubMedGoogle Scholar
- 36.Stewart MS, Spallholz JE, Neldner KH, Pence BC (1999) Selenium compounds have disparate abilities to impose oxidative stress and induce apoptosis. Free Radic Biol Med 26:42PubMedCrossRefGoogle Scholar
- 37.Raideep K, Sucheta S, Satyavan R (2003) Effect of sub-chronic selenium toxicosis on lipid peroxidation, glutathione redox cucle and antioxidant enzymes in calves. Vet Hum Toxicol 45(4):190–192Google Scholar
- 38.Misra S, Niyogi S (2009) Selenite causes cytotoxicity in rainbow trout (Oncorhynchus mykiss) hepatocytes by inducing oxidative stress. Toxicology In Vitro 31 (abstract)Google Scholar
- 39.Green DE, Albers PH (1997) Diagnostic criteria for selenium toxicosis in aquatic birds: histologic lesions. J Wildl Dis 33(3):385–404PubMedGoogle Scholar
- 40.Mu W, Tian Y, Piao J, Gu L, Yang X (2004) Studies on comparing the toxicity between sodium selenite and selenomethionine in rats. Wei Sheng Yan Jiu 33(6):700–703PubMedGoogle Scholar
- 41.Wang H, Zhang J, Yu H (2007) Elemental selenium at nano size possesses lower toxicity without compromising the fundamental effect on selenoenzymes: comparison with selenomethionine in mice. Free Radic Biol Med 42:1524–1533PubMedCrossRefGoogle Scholar
- 42.GX L, Hu H, Jiang C, Schuster T, Lu J (2007) Differential involvement of reactive oxygen species in apoptosis induced by two classes of selenium compounds in human prostate cancer cells. Int J Cancer 120(9):2034–2043CrossRefGoogle Scholar
- 43.Yunfeng Z, Piye N, Zhiyong G, Jin Y, Jing Y, Tangchun WU, Xuemin C (2007) Relationship between reactive oxygen species and sodium-selenite-induced DNA damage in HepG2 cells. Front Med China 1(3):327–332CrossRefGoogle Scholar
- 44.Zhou N, Xiao H, Li TK, Nur-E-Kamal A, Liu LF (2003) DNA damage mediated apoptosis induced by selenium compounds. J Biol Chem 278(32):29487–29495CrossRefGoogle Scholar
- 45.Kim YS, Jhon DY, Lee DY (2004) Involvement of ROS and JNK1 in selenite-induced apoptosis in Chang liver cells. Exp Mol Med 36:157–164PubMedGoogle Scholar
- 46.Kaur P, Bansal MP (2004) Effect of experimental oxidative stress on steroidogenesis and DNA damage in mouse testis. J Biomed Sci 11:391–397PubMedCrossRefGoogle Scholar
- 47.Drake EN (2006) Cancer chemoprevention: selenium as a prooxidant, not an antioxidant. Med Hypotheses 67:318–322PubMedCrossRefGoogle Scholar
- 48.Letavayov´a L, Vlˇckov´a V, Brozmanov´a J (2006) Selenium: From cancer prevention to DNA damage. Toxicology 227:1–14Google Scholar
- 49.Kim YY, Mahan DC (2001) Comparative effects of high dietary levels of organic and inorganic selenium on selenium toxicity of growing-finishing pigs. J Anim Sci 79:942PubMedGoogle Scholar
- 50.Xiang N, Zhao R, Zhong W (2009) Sodium selenite induces apoptosis by generation of superoxide via the mitochondrial-dependent pathway in human prostate cancer cells. Cancer Chemother Pharmacol 63:351–362PubMedCrossRefGoogle Scholar