In vivo radioprotection studies of 3,3′-diselenodipropionic acid, a selenocystine derivative

A. Kunwar, P. Bansal, S.J. Kumar, P.P. Bag, P. Paul, N.D. Reddy, L.B. Kumbhare, V.K. Jain, R.C. Chaubey, M.K. Unnikrishnan, K.I. Priyadarsini

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

3,3′-Diselenodipropionic acid (DSePA), a diselenide and a derivative of selenocystine, was evaluated for in vivo radioprotective effects in Swiss albino mice, at an intraperitoneal dose of 2 mg/kg body wt, for 5 days before whole-body exposure to γ-radiation. The radioprotective efficacy was evaluated by assessing protection of the hepatic tissue, the spleen, and the gastrointestinal (GI) tract and survival against sub- and supralethal doses of γ-radiation. DSePA inhibited radiation-induced hepatic lipid peroxidation, protein carbonylation, loss of hepatic function, and damage to the hepatic architecture. DSePA also attenuated the depletion of endogenous antioxidants such as glutathione, glutathione peroxidase, superoxide dismutase, and catalase in the livers of irradiated mice. DSePA also restored the radiation-induced reduction in villus height, crypt cell numbers, and spleen cellularity, indicating protective effects on the GI tract and the hematopoietic system. The results from single-cell gel electrophoresis of the peripheral blood leukocytes showed that DSePA can attenuate radiation-induced DNA damage. The mRNA expression analysis of genes revealed that DSePA augmented GADD45α and inhibited p21 in both spleen and liver tissues. DSePA also inhibited radiation-induced apoptosis in the spleen and reversed radiation-induced alterations in the expression of the proapoptotic BAX and the antiapoptotic Bcl-2 genes. In line with these observations, DSePA improved the 30-day survival of irradiated mice by 35.3%. In conclusion, these findings clearly confirm that DSePA exhibits protective effects against whole-body γ-radiation and the probable mechanisms of action involve the maintenance of antioxidant enzymes, prophylactic action through the attenuation of the DNA damage, and inhibition of apoptosis. © 2009 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)399-410
Number of pages12
JournalFree Radical Biology and Medicine
Volume48
Issue number3
DOIs
Publication statusPublished - 2010
Externally publishedYes

Fingerprint

Derivatives
Acids
Radiation
Liver
Spleen
DNA Damage
Gastrointestinal Tract
Antioxidants
Genes
Protein Carbonylation
Tissue
Apoptosis
bcl-2 Genes
selenocystine
Carbonylation
Hematopoietic System
Comet Assay
Whole-Body Irradiation
DNA
Glutathione Peroxidase

Cite this

Kunwar, A., Bansal, P., Kumar, S. J., Bag, P. P., Paul, P., Reddy, N. D., ... Priyadarsini, K. I. (2010). In vivo radioprotection studies of 3,3′-diselenodipropionic acid, a selenocystine derivative. Free Radical Biology and Medicine, 48(3), 399-410. https://doi.org/10.1016/j.freeradbiomed.2009.11.009
Kunwar, A. ; Bansal, P. ; Kumar, S.J. ; Bag, P.P. ; Paul, P. ; Reddy, N.D. ; Kumbhare, L.B. ; Jain, V.K. ; Chaubey, R.C. ; Unnikrishnan, M.K. ; Priyadarsini, K.I. / In vivo radioprotection studies of 3,3′-diselenodipropionic acid, a selenocystine derivative. In: Free Radical Biology and Medicine. 2010 ; Vol. 48, No. 3. pp. 399-410.
@article{de1be2ba2c9846d4a301e605265c92ff,
title = "In vivo radioprotection studies of 3,3′-diselenodipropionic acid, a selenocystine derivative",
abstract = "3,3′-Diselenodipropionic acid (DSePA), a diselenide and a derivative of selenocystine, was evaluated for in vivo radioprotective effects in Swiss albino mice, at an intraperitoneal dose of 2 mg/kg body wt, for 5 days before whole-body exposure to γ-radiation. The radioprotective efficacy was evaluated by assessing protection of the hepatic tissue, the spleen, and the gastrointestinal (GI) tract and survival against sub- and supralethal doses of γ-radiation. DSePA inhibited radiation-induced hepatic lipid peroxidation, protein carbonylation, loss of hepatic function, and damage to the hepatic architecture. DSePA also attenuated the depletion of endogenous antioxidants such as glutathione, glutathione peroxidase, superoxide dismutase, and catalase in the livers of irradiated mice. DSePA also restored the radiation-induced reduction in villus height, crypt cell numbers, and spleen cellularity, indicating protective effects on the GI tract and the hematopoietic system. The results from single-cell gel electrophoresis of the peripheral blood leukocytes showed that DSePA can attenuate radiation-induced DNA damage. The mRNA expression analysis of genes revealed that DSePA augmented GADD45α and inhibited p21 in both spleen and liver tissues. DSePA also inhibited radiation-induced apoptosis in the spleen and reversed radiation-induced alterations in the expression of the proapoptotic BAX and the antiapoptotic Bcl-2 genes. In line with these observations, DSePA improved the 30-day survival of irradiated mice by 35.3{\%}. In conclusion, these findings clearly confirm that DSePA exhibits protective effects against whole-body γ-radiation and the probable mechanisms of action involve the maintenance of antioxidant enzymes, prophylactic action through the attenuation of the DNA damage, and inhibition of apoptosis. {\circledC} 2009 Elsevier Inc. All rights reserved.",
author = "A. Kunwar and P. Bansal and S.J. Kumar and P.P. Bag and P. Paul and N.D. Reddy and L.B. Kumbhare and V.K. Jain and R.C. Chaubey and M.K. Unnikrishnan and K.I. Priyadarsini",
note = "Cited By :52 Export Date: 10 November 2017 CODEN: FRBME Correspondence Address: Unnikrishnan, M.K.; Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal, 576104, India; email: mkunnikrishnan@gmail.com Chemicals/CAS: DNA, 9007-49-2; catalase, 9001-05-2; glutathione, 70-18-8; glutathione peroxidase, 9013-66-5; lipid, 66455-18-3; protein bcl 2, 219306-68-0; protein p21, 85306-28-1; selenocystine, 1464-43-3, 2897-21-4, 29621-88-3; superoxide dismutase, 37294-21-6, 9016-01-7, 9054-89-1; 3,3'-diselenodipropionic acid; Antioxidants; Catalase, 1.11.1.6; Glutathione, 70-18-8; Glutathione Peroxidase, 1.11.1.9; Propionic Acids; Radiation-Protective Agents; Selenium Compounds; Superoxide Dismutase, 1.15.1.1 References: Andreassen, C.N., Grau, C., Lindegaard, J.C., Chemical radioprotection: a critical review of amifostine as a cytoprotector in radiotherapy (2008) Semin. Radiat. Oncol., 13, pp. 62-72; Riley, P.A., Free radicals in biology: oxidative stress and the effects of ionizing radiation (1994) Int. J. Radiat. Biol., 65, pp. 27-33; Weiss, J.F., Simic, M.G., Perspectives in radioprotection (1988) Pharmacol. Ther., 39, pp. 1-414; Weiss, J.F., Kumar, K.S., Walden, T.L., Neta, R., Landauer, M.R., Clark, E.P., Advances in radioprotection through the use of combined agent regimens (1990) Int. J. Radiat. Biol., 57, pp. 709-722; Weiss, J.F., Landauer, M.R., Protection against ionizing radiation by antioxidant nutrients and phytochemicals (2003) Toxicology, 189, pp. 1-20; Rosenfield, I., Beath, O.A., (1964) Selenium: Geotoxicity, Biochemistry, Toxicity and Nutrition, , Academic Press, New York; Brenneisen, P., Steinbrenner, H., Sies, H., Selenium, oxidative stress, and health aspects (2005) Mol. Aspects Med., 26, pp. 256-267; Rayman, M.P., The importance of selenium to human health (2000) Lancet, 356, pp. 233-241; Tapiero, H., Townsen, D.M., Tew, K.D., The antioxidant role of selenium and selenol-compounds (2003) Biomed. Pharmacother., 57, pp. 134-144; Venardos, K., Harrison, G., Headrick, J., Perkins, A., Effects of dietary selenium on glutathione peroxidase and thioredoxin reductase activity and recovery from cardiac ischemia-reperfusion (2004) J. Trace Elem. Med. Biol., 18, pp. 81-88; Nichter, M., Thompson, J.J., For my wellness, not just my illness: North Americans use of dietary supplements (2006) Cult. Med. Psychiatry, 30, pp. 175-222; Bradburn, M.J., Deeks, J.J., Berlin, J.A., Localio, A.R., Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled trial (1996) JAMA, 276, pp. 1957-1963; Vunta, H., Davis, F., Palempalli, U.D., Bhat, D., Arne, R.J., Thompson, J.T., Peterson, D.G., Prabhu, K.S., The anti-inflammatory effects of selenium are mediated through 15-deoxy-Δ12,14-prostaglandin J2 in macrophages (2007) J. Biol. Chem., 282, pp. 17964-17973; Arteel, G.E., Sies, H., The biochemistry of selenium and the glutathione system (2001) Environ. Toxicol. Pharmacol., 10, pp. 153-158; Sies, H., Arteel, G.E., Interaction of peroxynitrite with selenoproteins and glutathione peroxidase mimics (2000) Free Radic. Biol. Med., 28, pp. 1451-1455; Papp, L.V., Lu, J., Holmgren, A., Khanna, K.K., From selenium to selenoproteins: synthesis, identity and their role in human health (2007) Antioxid. Redox Signaling, 9, pp. 775-806; Mugesh, G., du Mont, W.-W., Sies, H., Chemistry of biologically important synthetic organoselenium compounds (2001) Chem. Rev., 101, pp. 2125-2179; Kunwar, A., Mishra, B., Barik, A., Kumbhare, L.B., Pandey, R., Jain, V.K., Priyadarsini, K.I., 3,3′-Diselenodipropionic acid, an efficient peroxyl radical scavenger and a GPx mimic, protects erythrocytes (RBCs) from AAPH-induced hemolysis (2007) Chem. Res. Toxicol., 20, pp. 1482-1487; Mishra, B., Barik, A., Kunwar, A., Kumbhare, L.B., Priyadarsini, K.I., Jain, V.K., Correlating the GPx activity of selenocystine derivatives with one-electron redox reactions (2008) Phosphorus Sulfur Silicon, 183, pp. 1018-1025; Tak, J.K., Park, J.W., The use of ebselen for radioprotection in cultured cells and mice (2009) Free Radic. Biol. Med., 46, pp. 1177-1185; Prabhakar, K.R., Veerapur, V.P., Bansal, P., Parihar, V.K., Reddy, K.M., Kumar, P.B., Priyadarsini, K.I., Unnikrishnan, M.K., Antioxidant and radioprotective effect of the active fraction of Pilea microphylla (L.) ethanolic extract (2007) Chem. Biol. Interact., 165, pp. 22-32; Kunwar, A., Narang, H., Priyadarsini, K.I., Krishna, M., Pandey, R., Sainis, K.B., Delayed activation of PKCδ and NFκB and higher radioprotection in splenic lymphocytes by copper(II)-curcumin (1:1) complex as compared to curcumin (2007) J. Cell. Biochem., 102, pp. 1214-1224; Abei, H., Catalase in vitro (1984) Methods Enzymol., 105, pp. 121-126; Sreejayan, N., Rao, M.N.A., Priyadarsini, K.I., Devasagayam, T.P.A., Inhibition of radiation induced lipid peroxidation by curcumin (1997) Int. J. Pharm., 151, pp. 127-130; Sedlak, J., Lindsay, R., Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent (1968) Anal. Biochem., 25, pp. 192-205; Oliver, C.N., Ahn, B., Moerman, E.J., Goldstein, S., Stadtman, E.R., Age-related changes in oxidized proteins (1987) J. Biol. Chem., 262, pp. 5488-5491; Reitman, S., Frankel, S.A., Colourimetric method for the determination of serum oxaloacetic and glutamic pyruvic transaminases (1957) Am. J. Clin. Pathol., 28, pp. 56-63; Mansour, H.H., Hafez, H.F., Fahmy, N.M., Hanafi, N., Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats (2008) Biochem. Pharmacol., 75, pp. 773-780; Sandhya, T., Lathika, K.M., Pandey, B.N., Bhilwade, H.N., Chaubey, R.C., Priyadarsini, K.I., Mishra, K.P., Protection against radiation oxidative damage in mice by Triphala (2006) Mutat. Res., 609, pp. 17-25; Mehata, S., Mehata, L., Mongia, S.P., Effect of whole body X-irradiation on liver of Swiss albino mice (1975) Int. J. Exp. Biol., 13, pp. 73-75; Samini, M., Dehpour, A.R., Hajinabi, K., The effect of lithium on acute toxicity of carbamazepine in mice (1997) Acta Med. Iran, 35, pp. 74-76; Katzung, B.G., (1988) Basic and Clinical Pharmacology, pp. 404-405. , Academic Press, London; Weiss, J.F., Srinivasan, V., Kumar, K.S., Landauer, M.R., Radioprotection by metals: selenium (1992) Adv. Space Res., 12, pp. 23-231; Weiss, J.F., Srinivasan, V., Kumar, K.S., Landauer, M.R., Patchen, M.L., Radioprotection by selenium compounds (1994) Trace Elements and Free Radicals in Oxidative Diseases, pp. 211-222. , Favier A.E., Neve J., and Fauve P. (Eds), Am. Oil Chem. Soc., Champaign, IL; Diamond, A.M., Dale, P., Murray, J.L., Gardina, D.J., The inhibition of radiation induced mutagenesis by the combined effects of selenium and the aminothiol WR-1065 (1996) Mutat. 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year = "2010",
doi = "10.1016/j.freeradbiomed.2009.11.009",
language = "English",
volume = "48",
pages = "399--410",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "3",

}

Kunwar, A, Bansal, P, Kumar, SJ, Bag, PP, Paul, P, Reddy, ND, Kumbhare, LB, Jain, VK, Chaubey, RC, Unnikrishnan, MK & Priyadarsini, KI 2010, 'In vivo radioprotection studies of 3,3′-diselenodipropionic acid, a selenocystine derivative', Free Radical Biology and Medicine, vol. 48, no. 3, pp. 399-410. https://doi.org/10.1016/j.freeradbiomed.2009.11.009

In vivo radioprotection studies of 3,3′-diselenodipropionic acid, a selenocystine derivative. / Kunwar, A.; Bansal, P.; Kumar, S.J.; Bag, P.P.; Paul, P.; Reddy, N.D.; Kumbhare, L.B.; Jain, V.K.; Chaubey, R.C.; Unnikrishnan, M.K.; Priyadarsini, K.I.

In: Free Radical Biology and Medicine, Vol. 48, No. 3, 2010, p. 399-410.

Research output: Contribution to journalArticle

TY - JOUR

T1 - In vivo radioprotection studies of 3,3′-diselenodipropionic acid, a selenocystine derivative

AU - Kunwar, A.

AU - Bansal, P.

AU - Kumar, S.J.

AU - Bag, P.P.

AU - Paul, P.

AU - Reddy, N.D.

AU - Kumbhare, L.B.

AU - Jain, V.K.

AU - Chaubey, R.C.

AU - Unnikrishnan, M.K.

AU - Priyadarsini, K.I.

N1 - Cited By :52 Export Date: 10 November 2017 CODEN: FRBME Correspondence Address: Unnikrishnan, M.K.; Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal, 576104, India; email: mkunnikrishnan@gmail.com Chemicals/CAS: DNA, 9007-49-2; catalase, 9001-05-2; glutathione, 70-18-8; glutathione peroxidase, 9013-66-5; lipid, 66455-18-3; protein bcl 2, 219306-68-0; protein p21, 85306-28-1; selenocystine, 1464-43-3, 2897-21-4, 29621-88-3; superoxide dismutase, 37294-21-6, 9016-01-7, 9054-89-1; 3,3'-diselenodipropionic acid; Antioxidants; Catalase, 1.11.1.6; Glutathione, 70-18-8; Glutathione Peroxidase, 1.11.1.9; Propionic Acids; Radiation-Protective Agents; Selenium Compounds; Superoxide Dismutase, 1.15.1.1 References: Andreassen, C.N., Grau, C., Lindegaard, J.C., Chemical radioprotection: a critical review of amifostine as a cytoprotector in radiotherapy (2008) Semin. Radiat. Oncol., 13, pp. 62-72; Riley, P.A., Free radicals in biology: oxidative stress and the effects of ionizing radiation (1994) Int. J. Radiat. Biol., 65, pp. 27-33; Weiss, J.F., Simic, M.G., Perspectives in radioprotection (1988) Pharmacol. Ther., 39, pp. 1-414; Weiss, J.F., Kumar, K.S., Walden, T.L., Neta, R., Landauer, M.R., Clark, E.P., Advances in radioprotection through the use of combined agent regimens (1990) Int. J. Radiat. Biol., 57, pp. 709-722; Weiss, J.F., Landauer, M.R., Protection against ionizing radiation by antioxidant nutrients and phytochemicals (2003) Toxicology, 189, pp. 1-20; Rosenfield, I., Beath, O.A., (1964) Selenium: Geotoxicity, Biochemistry, Toxicity and Nutrition, , Academic Press, New York; Brenneisen, P., Steinbrenner, H., Sies, H., Selenium, oxidative stress, and health aspects (2005) Mol. Aspects Med., 26, pp. 256-267; Rayman, M.P., The importance of selenium to human health (2000) Lancet, 356, pp. 233-241; Tapiero, H., Townsen, D.M., Tew, K.D., The antioxidant role of selenium and selenol-compounds (2003) Biomed. Pharmacother., 57, pp. 134-144; Venardos, K., Harrison, G., Headrick, J., Perkins, A., Effects of dietary selenium on glutathione peroxidase and thioredoxin reductase activity and recovery from cardiac ischemia-reperfusion (2004) J. Trace Elem. Med. Biol., 18, pp. 81-88; Nichter, M., Thompson, J.J., For my wellness, not just my illness: North Americans use of dietary supplements (2006) Cult. Med. Psychiatry, 30, pp. 175-222; Bradburn, M.J., Deeks, J.J., Berlin, J.A., Localio, A.R., Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled trial (1996) JAMA, 276, pp. 1957-1963; Vunta, H., Davis, F., Palempalli, U.D., Bhat, D., Arne, R.J., Thompson, J.T., Peterson, D.G., Prabhu, K.S., The anti-inflammatory effects of selenium are mediated through 15-deoxy-Δ12,14-prostaglandin J2 in macrophages (2007) J. Biol. Chem., 282, pp. 17964-17973; Arteel, G.E., Sies, H., The biochemistry of selenium and the glutathione system (2001) Environ. Toxicol. Pharmacol., 10, pp. 153-158; Sies, H., Arteel, G.E., Interaction of peroxynitrite with selenoproteins and glutathione peroxidase mimics (2000) Free Radic. Biol. Med., 28, pp. 1451-1455; Papp, L.V., Lu, J., Holmgren, A., Khanna, K.K., From selenium to selenoproteins: synthesis, identity and their role in human health (2007) Antioxid. Redox Signaling, 9, pp. 775-806; Mugesh, G., du Mont, W.-W., Sies, H., Chemistry of biologically important synthetic organoselenium compounds (2001) Chem. Rev., 101, pp. 2125-2179; Kunwar, A., Mishra, B., Barik, A., Kumbhare, L.B., Pandey, R., Jain, V.K., Priyadarsini, K.I., 3,3′-Diselenodipropionic acid, an efficient peroxyl radical scavenger and a GPx mimic, protects erythrocytes (RBCs) from AAPH-induced hemolysis (2007) Chem. Res. Toxicol., 20, pp. 1482-1487; Mishra, B., Barik, A., Kunwar, A., Kumbhare, L.B., Priyadarsini, K.I., Jain, V.K., Correlating the GPx activity of selenocystine derivatives with one-electron redox reactions (2008) Phosphorus Sulfur Silicon, 183, pp. 1018-1025; Tak, J.K., Park, J.W., The use of ebselen for radioprotection in cultured cells and mice (2009) Free Radic. Biol. Med., 46, pp. 1177-1185; Prabhakar, K.R., Veerapur, V.P., Bansal, P., Parihar, V.K., Reddy, K.M., Kumar, P.B., Priyadarsini, K.I., Unnikrishnan, M.K., Antioxidant and radioprotective effect of the active fraction of Pilea microphylla (L.) ethanolic extract (2007) Chem. Biol. Interact., 165, pp. 22-32; Kunwar, A., Narang, H., Priyadarsini, K.I., Krishna, M., Pandey, R., Sainis, K.B., Delayed activation of PKCδ and NFκB and higher radioprotection in splenic lymphocytes by copper(II)-curcumin (1:1) complex as compared to curcumin (2007) J. Cell. Biochem., 102, pp. 1214-1224; Abei, H., Catalase in vitro (1984) Methods Enzymol., 105, pp. 121-126; Sreejayan, N., Rao, M.N.A., Priyadarsini, K.I., Devasagayam, T.P.A., Inhibition of radiation induced lipid peroxidation by curcumin (1997) Int. J. Pharm., 151, pp. 127-130; Sedlak, J., Lindsay, R., Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent (1968) Anal. Biochem., 25, pp. 192-205; Oliver, C.N., Ahn, B., Moerman, E.J., Goldstein, S., Stadtman, E.R., Age-related changes in oxidized proteins (1987) J. Biol. Chem., 262, pp. 5488-5491; Reitman, S., Frankel, S.A., Colourimetric method for the determination of serum oxaloacetic and glutamic pyruvic transaminases (1957) Am. J. Clin. Pathol., 28, pp. 56-63; Mansour, H.H., Hafez, H.F., Fahmy, N.M., Hanafi, N., Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats (2008) Biochem. Pharmacol., 75, pp. 773-780; Sandhya, T., Lathika, K.M., Pandey, B.N., Bhilwade, H.N., Chaubey, R.C., Priyadarsini, K.I., Mishra, K.P., Protection against radiation oxidative damage in mice by Triphala (2006) Mutat. Res., 609, pp. 17-25; Mehata, S., Mehata, L., Mongia, S.P., Effect of whole body X-irradiation on liver of Swiss albino mice (1975) Int. J. Exp. Biol., 13, pp. 73-75; Samini, M., Dehpour, A.R., Hajinabi, K., The effect of lithium on acute toxicity of carbamazepine in mice (1997) Acta Med. Iran, 35, pp. 74-76; Katzung, B.G., (1988) Basic and Clinical Pharmacology, pp. 404-405. , Academic Press, London; Weiss, J.F., Srinivasan, V., Kumar, K.S., Landauer, M.R., Radioprotection by metals: selenium (1992) Adv. Space Res., 12, pp. 23-231; Weiss, J.F., Srinivasan, V., Kumar, K.S., Landauer, M.R., Patchen, M.L., Radioprotection by selenium compounds (1994) Trace Elements and Free Radicals in Oxidative Diseases, pp. 211-222. , Favier A.E., Neve J., and Fauve P. (Eds), Am. Oil Chem. Soc., Champaign, IL; Diamond, A.M., Dale, P., Murray, J.L., Gardina, D.J., The inhibition of radiation induced mutagenesis by the combined effects of selenium and the aminothiol WR-1065 (1996) Mutat. 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PY - 2010

Y1 - 2010

N2 - 3,3′-Diselenodipropionic acid (DSePA), a diselenide and a derivative of selenocystine, was evaluated for in vivo radioprotective effects in Swiss albino mice, at an intraperitoneal dose of 2 mg/kg body wt, for 5 days before whole-body exposure to γ-radiation. The radioprotective efficacy was evaluated by assessing protection of the hepatic tissue, the spleen, and the gastrointestinal (GI) tract and survival against sub- and supralethal doses of γ-radiation. DSePA inhibited radiation-induced hepatic lipid peroxidation, protein carbonylation, loss of hepatic function, and damage to the hepatic architecture. DSePA also attenuated the depletion of endogenous antioxidants such as glutathione, glutathione peroxidase, superoxide dismutase, and catalase in the livers of irradiated mice. DSePA also restored the radiation-induced reduction in villus height, crypt cell numbers, and spleen cellularity, indicating protective effects on the GI tract and the hematopoietic system. The results from single-cell gel electrophoresis of the peripheral blood leukocytes showed that DSePA can attenuate radiation-induced DNA damage. The mRNA expression analysis of genes revealed that DSePA augmented GADD45α and inhibited p21 in both spleen and liver tissues. DSePA also inhibited radiation-induced apoptosis in the spleen and reversed radiation-induced alterations in the expression of the proapoptotic BAX and the antiapoptotic Bcl-2 genes. In line with these observations, DSePA improved the 30-day survival of irradiated mice by 35.3%. In conclusion, these findings clearly confirm that DSePA exhibits protective effects against whole-body γ-radiation and the probable mechanisms of action involve the maintenance of antioxidant enzymes, prophylactic action through the attenuation of the DNA damage, and inhibition of apoptosis. © 2009 Elsevier Inc. All rights reserved.

AB - 3,3′-Diselenodipropionic acid (DSePA), a diselenide and a derivative of selenocystine, was evaluated for in vivo radioprotective effects in Swiss albino mice, at an intraperitoneal dose of 2 mg/kg body wt, for 5 days before whole-body exposure to γ-radiation. The radioprotective efficacy was evaluated by assessing protection of the hepatic tissue, the spleen, and the gastrointestinal (GI) tract and survival against sub- and supralethal doses of γ-radiation. DSePA inhibited radiation-induced hepatic lipid peroxidation, protein carbonylation, loss of hepatic function, and damage to the hepatic architecture. DSePA also attenuated the depletion of endogenous antioxidants such as glutathione, glutathione peroxidase, superoxide dismutase, and catalase in the livers of irradiated mice. DSePA also restored the radiation-induced reduction in villus height, crypt cell numbers, and spleen cellularity, indicating protective effects on the GI tract and the hematopoietic system. The results from single-cell gel electrophoresis of the peripheral blood leukocytes showed that DSePA can attenuate radiation-induced DNA damage. The mRNA expression analysis of genes revealed that DSePA augmented GADD45α and inhibited p21 in both spleen and liver tissues. DSePA also inhibited radiation-induced apoptosis in the spleen and reversed radiation-induced alterations in the expression of the proapoptotic BAX and the antiapoptotic Bcl-2 genes. In line with these observations, DSePA improved the 30-day survival of irradiated mice by 35.3%. In conclusion, these findings clearly confirm that DSePA exhibits protective effects against whole-body γ-radiation and the probable mechanisms of action involve the maintenance of antioxidant enzymes, prophylactic action through the attenuation of the DNA damage, and inhibition of apoptosis. © 2009 Elsevier Inc. All rights reserved.

U2 - 10.1016/j.freeradbiomed.2009.11.009

DO - 10.1016/j.freeradbiomed.2009.11.009

M3 - Article

VL - 48

SP - 399

EP - 410

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 3

ER -