Effects of sodium selenite administration during diethylnitrosamine intoxication in rats

Effects of sodium selenite administration during diethylnitrosamine intoxication in rats

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Title: Effects of sodium selenite administration during diethylnitrosamine intoxication in rats
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Article_Title: Effects of sodium selenite administration during diethylnitrosamine intoxication in rats
Authors: Liliana Avasilcăi, Bogdan Gabriel Şlencu, Constantin Ciobanu, Rodica Cuciureanu
Affiliation: Department of Environmental and Food Chemistry, Faculty of Pharmacy University of Medicine and Pharmacy “Gr. T. Popa” Iaşi, Romania
Abstract: The aim of this study was to evaluate the toxicity of a single dose of 100 mg/kg body weight of NDEA and to compare the effects of selenium administration before and after the NDEA dose (pre- vs. post-treatment), on the evolution of some biochemical parameters. Male Wistar rats were divided into five groups (n=5): control group, NDEA group (NDEA: 100 mg/kg bw by gavage, single dose), NDEA + Se3 group (NDEA: 100 mg/kg bw by gavage, single dose + Se+4: 3 mg/kg bw by gavage, in the first four days), Se group (Se+4: 3 mg/kg bw by gavage, for four days) and Se3 + NDEA group (Se+4: 3 mg/kg bw by gavage, for four days before NDEA administration + NDEA: 100 mg/kg bw by gavage, single dose). The animals were sacrificed after ten days from NDEA administration and blood was collected. The biochemical parameters were determined using a RX Imola automatic analyzer. In the NDEA group uric acid, total bilirubin, direct bilirubin, HDL-cholesterol, LDL-cholesterol levels and ALT and AST activities were significantly increased compared to the control group. Total bilirubin, direct bilirubin, HDL-cholesterol and iron blood levels, as well as GGT and AST activities were significantly increased in NDEA+Se group, compared to the Se+NDEA group, whereas LDL-cholesterol levels and ALT activities were significantly increased in Se+NDEA group, compared to the NDEA+Se group. At this dose and observational period, NDEA was slightly toxic. The post-treatment with sodium selenite increased NDEA toxicity and was more severe than the pre-treatment.
Keywords: selenium, sodium selenite, diethylnitrosamine, biochemical parameters, rats
References: Aiub CA, Pinto LF, Felzenszwalb I, N-nitrosodiethylamine mutagenicity at low concentrations. Toxicol
Lett, 145, 36–45, 2003.
Aiub CA, Mazzei JL, Pinto LF, Felzenszwalb I, Evaluation of nitroreductase and acetyltransferase
participation in N-nitrosodiethylamine genotoxicity. Chem Biol Interact, 161(2), 146-154, 2006.
Altkofer W, Braune S, Ellendt K, Kettl-Gro¨mminger M, Steiner G, Migration of nitrosamines from rubber products are balloons and condoms harmful to the human health?. Mol Nutr FoodRes, 49, 235–238, 2005.
Alwahaibi N, Mohamed J, Alhamadani A, Supplementation of selenium reduces chemical hepatocarcinogenesis in male Sprague-Dawley rats. J Trace Elem Med Biol, 24(2), 119-123, 2010.
Banakar MC, Paramasivan SK, Chattopadhyay MB, Datta S, Chakraborty P, Chatterjee M, Kannan K,
Thygarajan E, 1alpha, 25-dihydroxyvitamin D3 prevents DNA damage and restores antioxidant enzymes in rat hepatocarcinogenesis induced by diethylnitrosamine and promoted by phenobarbital. World J Gastroenterol, 10(9), 1268-1275, 2004.
Bansal AK, Bansal M, Soni G, Bhatnagar D, Protective role of vitamin E pre-treatment on
N-nitrosodiethylamine induced oxidative stress in rat liver. Chem–Biol Interact, 156, 101–111, 2005.
El-Demerdash FM, Antioxidant effect of vitamin E and selenium on lipid peroxidation, enzyme activities and biochemical parameters in rats exposed to aluminium. J Trace Elem Med Biol, 18, 113-121, 2004.
Hord NG, Tang Y, Bryan NS, Food sources of nitrates and nitrites: the physiologic context for potential health benefits. Am J Clin Nutr, 90(1), 1-10, 2009.
Kim MR, Kim HS, Lee MS, Lee MJ, Jang JJ, Cell cycle protein profile of the hepatic stellate cells (HSCs) in dimethylnitrosamine-induced rat hepatic fibrosis. Exp Mol Med, 37(4), 335–342, 2005.
Levallois P, Ayotte P, van Maanen JM, Desrosiers T, Gingras S, Dallinga JW, Vermeer IT, Zee J, Poirier G, Excretion of volatile nitrosamines in a rural population in relation to food and drinking water consumption. Food Chem Toxicol, 38, 1013–1019, 2000.
Lijinsky W, N-nitroso compounds in the diet, Mutat Res. 443, 129–138, 1999.
Liu JG, Zhao HJ, Liu YJ, Wang XL, Effect of selenium-enriched malt on hepatocarcinogenesis,
paraneoplastic syndrome and the hormones regulating blood glucose in rats treated by diethylnitrosamine, 78, 2315-2321, 2006.
Ohsawa K, Nakagawa SY, Kimura M, Shimada C, Tsuda S, Kabasawa K, Kawaguci S, Sasaki YF, Detection
of in vivo genotoxicity of endogenously formed N-nitroso compounds and suppression by ascorbic
acid, teas and fruit juices. Mutat Res, 539, 565–576, 2003.
Raich PC, Lu JX, Thompson HJ, Combs Jr.GF, Selenium in cancer prevention: clinical issues and
implications. Cancer Invest, 19, 540–553, 2001.
Steinhoff D, Effect of diethylnitrosamine on the livers of rats after high oral doses administered at intervals varying between three and twenty-four days. Acta Hepato-Gastro, 22, 72, 1975.
Thirunavukkarasu C, Sakthisekaran D, Sodium selenite modulates tumour marker indices in
N-nitrosodiethylamine-initiated and phenobarbitalpromoted rat liver carcinogenesis. Cell Biochem
Funct, 21, 147-153, 2003.
Thirunavukkarasu C, Premkumar K, Sheriff AK, Sakthisekaran D, Sodium selenite enhances
glutathione peroxidase activity and DNA strand breaks in hepatoma induced by N-nitrosodiethylamine and promoted by phenobarbital. Mol Cell Biochem, 310, 129-139, 2008.
Thomson CD, Robinson MF, Urinary and fecal excretions and absorption of a large supplement of selenium: Superiority of selenate over selenite. Am J Clin Nutr, 44, 659-663, 1986.
Verna L, Whysner J, Williams GM, N-nitrosodiethylamine mechanistic data and risk asseessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. Pharmacol Ther, 71, 57-81, 1996.
Zeng HW, Combs Jr.GF, Selenium as an anticancer nutrient: roles in cell proliferation and tumor cell
invasion. J Nutr Biochem, 19, 1-7, 2008.
Read_full_article: pdf/21-2011/21-2-2011/SU21-2-2011Avasilcai.pdf
Correspondence: Cuciureanu Rodica, University of Medicine and Pharmacy Gr. T. Popa Iasi, 16 Universitatii Street, 700115, Iasi, Romania E-mail: rcuciur@yahoo.com

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Article Title: Effects of sodium selenite administration during diethylnitrosamine intoxication in rats
Authors: Liliana Avasilcăi, Bogdan Gabriel Şlencu, Constantin Ciobanu, Rodica Cuciureanu
Affiliation: Department of Environmental and Food Chemistry, Faculty of Pharmacy University of Medicine and Pharmacy “Gr. T. Popa” Iaşi, Romania
Abstract: The aim of this study was to evaluate the toxicity of a single dose of 100 mg/kg body weight of NDEA and to compare the effects of selenium administration before and after the NDEA dose (pre- vs. post-treatment), on the evolution of some biochemical parameters. Male Wistar rats were divided into five groups (n=5): control group, NDEA group (NDEA: 100 mg/kg bw by gavage, single dose), NDEA + Se3 group (NDEA: 100 mg/kg bw by gavage, single dose + Se+4: 3 mg/kg bw by gavage, in the first four days), Se group (Se+4: 3 mg/kg bw by gavage, for four days) and Se3 + NDEA group (Se+4: 3 mg/kg bw by gavage, for four days before NDEA administration + NDEA: 100 mg/kg bw by gavage, single dose). The animals were sacrificed after ten days from NDEA administration and blood was collected. The biochemical parameters were determined using a RX Imola automatic analyzer. In the NDEA group uric acid, total bilirubin, direct bilirubin, HDL-cholesterol, LDL-cholesterol levels and ALT and AST activities were significantly increased compared to the control group. Total bilirubin, direct bilirubin, HDL-cholesterol and iron blood levels, as well as GGT and AST activities were significantly increased in NDEA+Se group, compared to the Se+NDEA group, whereas LDL-cholesterol levels and ALT activities were significantly increased in Se+NDEA group, compared to the NDEA+Se group. At this dose and observational period, NDEA was slightly toxic. The post-treatment with sodium selenite increased NDEA toxicity and was more severe than the pre-treatment.
Keywords: selenium, sodium selenite, diethylnitrosamine, biochemical parameters, rats
References: Aiub CA, Pinto LF, Felzenszwalb I, N-nitrosodiethylamine mutagenicity at low concentrations. Toxicol
Lett, 145, 36–45, 2003.
Aiub CA, Mazzei JL, Pinto LF, Felzenszwalb I, Evaluation of nitroreductase and acetyltransferase
participation in N-nitrosodiethylamine genotoxicity. Chem Biol Interact, 161(2), 146-154, 2006.
Altkofer W, Braune S, Ellendt K, Kettl-Gro¨mminger M, Steiner G, Migration of nitrosamines from rubber products are balloons and condoms harmful to the human health?. Mol Nutr FoodRes, 49, 235–238, 2005.
Alwahaibi N, Mohamed J, Alhamadani A, Supplementation of selenium reduces chemical hepatocarcinogenesis in male Sprague-Dawley rats. J Trace Elem Med Biol, 24(2), 119-123, 2010.
Banakar MC, Paramasivan SK, Chattopadhyay MB, Datta S, Chakraborty P, Chatterjee M, Kannan K,
Thygarajan E, 1alpha, 25-dihydroxyvitamin D3 prevents DNA damage and restores antioxidant enzymes in rat hepatocarcinogenesis induced by diethylnitrosamine and promoted by phenobarbital. World J Gastroenterol, 10(9), 1268-1275, 2004.
Bansal AK, Bansal M, Soni G, Bhatnagar D, Protective role of vitamin E pre-treatment on
N-nitrosodiethylamine induced oxidative stress in rat liver. Chem–Biol Interact, 156, 101–111, 2005.
El-Demerdash FM, Antioxidant effect of vitamin E and selenium on lipid peroxidation, enzyme activities and biochemical parameters in rats exposed to aluminium. J Trace Elem Med Biol, 18, 113-121, 2004.
Hord NG, Tang Y, Bryan NS, Food sources of nitrates and nitrites: the physiologic context for potential health benefits. Am J Clin Nutr, 90(1), 1-10, 2009.
Kim MR, Kim HS, Lee MS, Lee MJ, Jang JJ, Cell cycle protein profile of the hepatic stellate cells (HSCs) in dimethylnitrosamine-induced rat hepatic fibrosis. Exp Mol Med, 37(4), 335–342, 2005.
Levallois P, Ayotte P, van Maanen JM, Desrosiers T, Gingras S, Dallinga JW, Vermeer IT, Zee J, Poirier G, Excretion of volatile nitrosamines in a rural population in relation to food and drinking water consumption. Food Chem Toxicol, 38, 1013–1019, 2000.
Lijinsky W, N-nitroso compounds in the diet, Mutat Res. 443, 129–138, 1999.
Liu JG, Zhao HJ, Liu YJ, Wang XL, Effect of selenium-enriched malt on hepatocarcinogenesis,
paraneoplastic syndrome and the hormones regulating blood glucose in rats treated by diethylnitrosamine, 78, 2315-2321, 2006.
Ohsawa K, Nakagawa SY, Kimura M, Shimada C, Tsuda S, Kabasawa K, Kawaguci S, Sasaki YF, Detection
of in vivo genotoxicity of endogenously formed N-nitroso compounds and suppression by ascorbic
acid, teas and fruit juices. Mutat Res, 539, 565–576, 2003.
Raich PC, Lu JX, Thompson HJ, Combs Jr.GF, Selenium in cancer prevention: clinical issues and
implications. Cancer Invest, 19, 540–553, 2001.
Steinhoff D, Effect of diethylnitrosamine on the livers of rats after high oral doses administered at intervals varying between three and twenty-four days. Acta Hepato-Gastro, 22, 72, 1975.
Thirunavukkarasu C, Sakthisekaran D, Sodium selenite modulates tumour marker indices in
N-nitrosodiethylamine-initiated and phenobarbitalpromoted rat liver carcinogenesis. Cell Biochem
Funct, 21, 147-153, 2003.
Thirunavukkarasu C, Premkumar K, Sheriff AK, Sakthisekaran D, Sodium selenite enhances
glutathione peroxidase activity and DNA strand breaks in hepatoma induced by N-nitrosodiethylamine and promoted by phenobarbital. Mol Cell Biochem, 310, 129-139, 2008.
Thomson CD, Robinson MF, Urinary and fecal excretions and absorption of a large supplement of selenium: Superiority of selenate over selenite. Am J Clin Nutr, 44, 659-663, 1986.
Verna L, Whysner J, Williams GM, N-nitrosodiethylamine mechanistic data and risk asseessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. Pharmacol Ther, 71, 57-81, 1996.
Zeng HW, Combs Jr.GF, Selenium as an anticancer nutrient: roles in cell proliferation and tumor cell
invasion. J Nutr Biochem, 19, 1-7, 2008.
*Correspondence: Cuciureanu Rodica, University of Medicine and Pharmacy Gr. T. Popa Iasi, 16 Universitatii Street, 700115, Iasi, Romania E-mail: rcuciur@yahoo.com