Radioprotection by copper and zinc complexes of 5-aminosalicylic acid: A preliminary study

S.K. Mantena, M.K. Unnikrishnan, K. Chandrasekharan

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The effect of copper and zinc complexes of 5-aminosalicylic acid (hereafter referred to as Cu-5ASA and Zn-5ASA, respectively) against whole-body gamma radiation-induced cytotoxicity was studied in Swiss albino mice. Protection against lethal irradiation was evaluated from 30 day mouse survival (10 Gy) and endogenous spleen colony assay (11 Gy); and against sublethal dose (4 Gy) was assessed from gamma irradiation (RT)-induced formation of micronuclei in the mouse bone marrow 24 h postirradiation. Pretreatment with either Cu-5ASA (2.5-9 mg/kg) or Zn-5ASA (3.5-14 mg/kg) intraperitoneally (i.p.) delayed and reduced percentage mortality in mice exposed to 10 Gy RT. The doses 9 mg/kg for Cu-5ASA and 7 mg/kg for Zn-5ASA were found to be the most effective dose in preventing RT-induced weight loss and reducing percentage mortality. Both the drugs also caused an increase in the endogenous spleen colonies in mouse exposed to 11 Gy RT. At sublethal doses of RT, pretreatment with either Cu-5ASA or Zn-5ASA resulted in a significant decrease in the RT-induced micronucleated polychromatic erythrocytes and normochromatic erythrocytes (MPCEs and MNCEs) and an increase in the ratio of PCE to NCE (P/N), at 24 h postirradiation. These results show that both Cu-5ASA and Zn-5ASA are effective in protecting normal tissues against lethal and sublethal doses of RT. Further pretreatment with either Cu-5ASA or Zn-5ASA enhanced the survival of tumor-bearing mice (Ehrlich's ascites carcinoma) exposed to 7.5 Gy RT. In fact, both the complexes caused an increase in the mean and average survival times (MST and AST) when compared to the irradiated control, suggesting a synergetic effect of these drugs with radiation in causing cytotoxicity to the tumor cells. The data clearly indicate that both Cu-5ASA and Zn-5ASA significantly reduced the deleterious effect of radiation and hence could be useful agents in reducing the side effects of therapeutic radiation. © 2008 by Begell House, Inc.
Original languageEnglish
Pages (from-to)123-134
Number of pages12
JournalJournal of Environmental Pathology, Toxicology and Oncology
Volume27
Issue number2
Publication statusPublished - 2008

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Mesalamine
Zinc
Copper
Cytotoxicity
Radiation
Tumors
Bearings (structural)
Irradiation
Radiation Effects
Gamma rays
Pharmaceutical Preparations
Dosimetry
Assays
Bone
Spleen
Erythrocytes
Cells
Tissue
Mortality
Whole-Body Irradiation

Cite this

Mantena, S.K. ; Unnikrishnan, M.K. ; Chandrasekharan, K. / Radioprotection by copper and zinc complexes of 5-aminosalicylic acid: A preliminary study. In: Journal of Environmental Pathology, Toxicology and Oncology. 2008 ; Vol. 27, No. 2. pp. 123-134.
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title = "Radioprotection by copper and zinc complexes of 5-aminosalicylic acid: A preliminary study",
abstract = "The effect of copper and zinc complexes of 5-aminosalicylic acid (hereafter referred to as Cu-5ASA and Zn-5ASA, respectively) against whole-body gamma radiation-induced cytotoxicity was studied in Swiss albino mice. Protection against lethal irradiation was evaluated from 30 day mouse survival (10 Gy) and endogenous spleen colony assay (11 Gy); and against sublethal dose (4 Gy) was assessed from gamma irradiation (RT)-induced formation of micronuclei in the mouse bone marrow 24 h postirradiation. Pretreatment with either Cu-5ASA (2.5-9 mg/kg) or Zn-5ASA (3.5-14 mg/kg) intraperitoneally (i.p.) delayed and reduced percentage mortality in mice exposed to 10 Gy RT. The doses 9 mg/kg for Cu-5ASA and 7 mg/kg for Zn-5ASA were found to be the most effective dose in preventing RT-induced weight loss and reducing percentage mortality. Both the drugs also caused an increase in the endogenous spleen colonies in mouse exposed to 11 Gy RT. At sublethal doses of RT, pretreatment with either Cu-5ASA or Zn-5ASA resulted in a significant decrease in the RT-induced micronucleated polychromatic erythrocytes and normochromatic erythrocytes (MPCEs and MNCEs) and an increase in the ratio of PCE to NCE (P/N), at 24 h postirradiation. These results show that both Cu-5ASA and Zn-5ASA are effective in protecting normal tissues against lethal and sublethal doses of RT. Further pretreatment with either Cu-5ASA or Zn-5ASA enhanced the survival of tumor-bearing mice (Ehrlich's ascites carcinoma) exposed to 7.5 Gy RT. In fact, both the complexes caused an increase in the mean and average survival times (MST and AST) when compared to the irradiated control, suggesting a synergetic effect of these drugs with radiation in causing cytotoxicity to the tumor cells. The data clearly indicate that both Cu-5ASA and Zn-5ASA significantly reduced the deleterious effect of radiation and hence could be useful agents in reducing the side effects of therapeutic radiation. {\circledC} 2008 by Begell House, Inc.",
author = "S.K. Mantena and M.K. Unnikrishnan and K. Chandrasekharan",
note = "Cited By :4 Export Date: 10 November 2017 CODEN: JEPOE Correspondence Address: Unnikrishnan, M. K.; Department of Pharmacology, College of Pharmaceutical Sciences, Manipal-576 119, India; email: mkunnikrishnan@gmail.com Chemicals/CAS: mesalazine, 89-57-6; Aminosalicylic Acids; Copper, 7440-50-8; Radiation-Protective Agents; Zinc, 7440-66-6 Manufacturers: Sigma, United States References: Barcellos-Hoff, M.H., Park, C., Wright, E.G., Radiation and the microenvironment - tumorigenesis and therapy (2005) Nature Rev Cancer, 58, pp. 867-875; Sonntag, V.C., (1987) The chemical basis of radiation biology, , London: Taylor and Francis;; Joshi, R., Kumar, S., Unnikrishnan, M., Mukherjee, T., Free radical scavenging reactions of sulfasalazine, 5-aminosalicylic acid and sulfapyridine: Mechanistic aspects and antioxidant activity (2005) Free Radic Res, 39, pp. 1163-1172; Sudheer Kumar, M., Unnikrishnan, M.K., Uma Devi, P., Effect of 5-aminosalicylic acid on radiation-induced micronuclei in mouse bone marrow (2003) Mutat Res, 527, pp. 7-14; Unnikrishnan, M.K., Sudheer Kumar, M., Devi, U., Joshi, R., Radha, V., Mukherjee, T., 5-aminosalicylic acid and sulfasalazine reduces gamma radiation-induced oxidative stress: Involvement of p53/p21 pathway (2005) Free Radic Biol Med, 39 (SUPPL. 1), pp. S119; Kiremit-Korkut, N., Korkut, C., Bilge, H., Protective effect of mesalamine against oxidative injury in a rat model of radiation rectitis (2004) Curr Ther Res, 65, pp. 433-442; Fridovich, I., Superoxide dismutases (1986) Adv. Enzymol. Relat. Areas Mol. Biol, 58, pp. 61-97; Gee, C.A., Kittridge, K.J., Willson, R.L., Peroxy free radicals, enzymes and radiation damage: Sensitisation by oxygen and protection by superoxide dismutase and antioxidants (1985) Br J Radiol, 58, pp. 251-256; Omar, B.A., Flores, S.C., Mc Cord, J.M., Superoxide dismutase: Pharmacological developments and applications (1992) Adv Pharmacol, 23, pp. 109-161; Sorenson, J.R.J., Soderberg, L.S., Chang, L.W., Radiation protection and radiation recovery with essential metalloelement chelates (1995) Proc Soc Exp Biol Med, 210, pp. 191-204; Czapski, G., Goldstein, S., Requirements for SOD mimics operating in vitro to work also in vivo (1991) Free Radic Res Comm, pp. 12-13,167-171; Riley, D.P., Functional mimics of superoxide dismutase enzymes as therapeutic agents (1999) Chem Rev, 99, pp. 2573-2587; Koiram, P.R., Veerapur, V.P., Kunwar, A., Mishra, B., Barik, A., Priyadarsini, I.K., Mazhuvancherry, U.K., Effect of curcumin and curcumin copper complex (1:1) on radiation-induced changes of anti-oxidant enzymes levels in the livers of Swiss albino mice (2007) J Radiat Res, 48, pp. 241-245; Sorenson, J.R.J., Cu, F., Mn, and Zn chelates offer a medicinal chemistry approach to overcoming radiation injury (2002) Curr Med Chem, 9, pp. 639-662; Sorenson, J.R.J., Copper chelates as possible active forms of the antiarthritic agents (1976) J Med Chem, 19, pp. 135-148; Ganasoundari, A., Uma Devi, P., Rao, M.N.A., Protection against radiation-induced chromosome damage in mouse bone marrow by ocimum sanctum (1997) Mutat Res, 373, pp. 271-276; Sorensen, K.J., Zetterberg, L.A., Nelson, D.O., Grawe, J., Tucker, J.D., The in vivo dose rate effect of chronic gamma radiation in mice: Translocation and micronucleus analyses (2000) Mutat Res, 457, pp. 125-136; Joksic, G., Petrovic, S., Ilic, Z., Age-related changes in radiation-induced micronuclei among healthy adults (2004) Brazilian J Medical Biol Res, 37, pp. 1111-1117; Schmitz, A., Bayer, J., Dechamps, N., Thomas, G., Intrinsic susceptibility to radiation-induced apoptosis of human lymphocyte subpopulations (2003) Int J Radiat Oncol Biol Phys, 57, pp. 769-778; Scott, D., Spreadborough, A.R., Roberts, S.A., Less G2 arrest in irradiated cells of breast cancer patients than in female controls: A contribution to their enhanced chromosomal radiosensitivity? (2003) Int J Radiat Biol, 79, pp. 405-411; Uma Devi, P., Ganasoundari, A., Vrinda, B., Srinivasan, K.K., Unnikrishnan, M.K., Radiation protection by the ocimum flavonoids orientin and vicenin: Mechanisms of action (2000) Radiat Res, 154, pp. 455-460; Prabhakar, K.R., Veerapur, V.P., Parihar, K.V., Priyadarsini, K.I., Rao, B.S., Unnikrishnan, M.K., Evaluation and optimization of radioprotective activity of coronopus didymus Linn. in gamma-irradiated mice (2006) Int J Radiat Biol, 82, pp. 525-536; Jagetia, G.C., Ganapathi, N.G., Effect of copperglycinate on the radiation induced micronuclei formation in mice bone marrow (1990) Radiat Environ Biophys, 29, pp. 115-118; Ghosh, M.N., (1994) Fundamentals of Experimental Pharmacology, pp. 153-157. , Calcutta: Scientific Book Agency;; Geigy JR. Documents Geigy scientific tables. London, UK: J. Board & Co. Ltd.; 1956, p. 26-48; Uma Devi, P., Ganasoundari, A., Rao, B.S.S., Srinivasan, K.K., In vivo radioprotection by ocimum flavonoids: Survival of mice (1999) Radiat Res, 151, pp. 74-78; Satyamitra, M., Uma Devi, P., Murase, H., Kagiya, V.T., In vivo postirradiation protection by a vitamin E analog, alpha-TMG (2003) Radiat Res, 160, pp. 655-661; Uma Devi, P., Prasanna, P.G.S., Comparative radioprotection of mouse haemopoetic study by some thiols and a polysaccharide (1995) Proc Natl Acad Sci Lett, 65, pp. 1-4; Jagetia, G.C., Baliga, M.S., Modulation of antineoplastic activity of cyclophosphamide by Alstonia scholaris in the Ehrlich ascites carcinoma-bearing mice (2003) J Exp Ther Oncol, 3, pp. 272-282; Coleman, C.N., Blakely, W.F., Fike, J.R., Mac Vitte, T.J., Metting, N.F., Mitchell, J.B., Moulder, J.E., Wong, R.S.L., Molecular and cellular biology of moderate-dose (1-10 Gy) radiation and potential mechanisms of radiation protection: Report of a workshop at Bethesda, Maryland, December 17-18, 2001 (2003) Radiat Res, 159, pp. 12-834; Matsubara, J., Tajima, Y., Karasawa, M., Promotion of radioresistance by metallothionine induction prior to irradiation (1981) Environ Res, 35, pp. 66-74; Henderson, T.D., Burt, R.L., Kaufman, S.E., Willingham, W.M., Sorenson, J.R.J., Radiorecovery activity of manganese (III)2(II)(U3-0)(U-3,5- diisopropylsalicylate)6 (1993) Radiat Res, 136, pp. 126-129; Floersheim, G.L., Bieri, A., Further studies on selective radioprotection by organic zinc salt and synergism of zinc aspartate with WR (1990) Br J Radiol, 63, pp. 468-475; Soderberg, L.S., Barnett, J.B., Baker, M.L., Salari, H., Sorenson, J.R.J., Copper(II)(3,5-diisopropylsalicylate) 2 accelerates recovery of B and T cell reactivity following irradiation (1987) Scand. J. Immunol, 26, pp. 495-502; Soderberg, L.S., Barnett, J.B., Baker, M.L., Salari, H., Sorenson, J.R.J., Copper(II)2(3,5-diisopropylsalicylate)4 stimulates hemopoiesis in normal and irradiated mice (1988) Exp Hematol, 16, pp. 577-580; Soderberg, L.S., Barnett, J.B., Baker, M.L., Salari, H., Sorenson, J.R.J., Post irradiation treatment with copper(II)2(3,5-diisopropylsalicylate) 4 enhances radiation recovery and hemopoietic regeneration (1990) Exp Hematol, 18, pp. 801-805; Floersheim, G.L., Chiodetti, N., Bieri, A., Differential radioprotection of bone marrow and tumour cells by zinc aspartate (1988) Br J Radiol, 61, pp. 501-508; Roy, M.B., Mandal, P.C., Bhattacharyya, S.N., Radiosensitization of thymine by copper(II) and nickel(II) complexes of metronidazole (1996) Int J Radiat Biol, 69, pp. 471-480; Savoye, C., Sabattier, R., Charlier, M., Spotheim, M.M., Sequence-modulated radiosensitization of DNA by copper ions (1996) Int J Radiat Biol, 70, pp. 189-198; Har-El, R., Chevion, M., Zinc(II) protects against metal-mediated free radical induced damage: Studies on single and double-strand DNA breakage (1991) Free Radic Res Commun, 2, pp. 509-515",
year = "2008",
language = "English",
volume = "27",
pages = "123--134",
journal = "Journal of Environmental Pathology, Toxicology and Oncology",
issn = "0731-8898",
publisher = "Begell House Inc.",
number = "2",

}

Radioprotection by copper and zinc complexes of 5-aminosalicylic acid: A preliminary study. / Mantena, S.K.; Unnikrishnan, M.K.; Chandrasekharan, K.

In: Journal of Environmental Pathology, Toxicology and Oncology, Vol. 27, No. 2, 2008, p. 123-134.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Radioprotection by copper and zinc complexes of 5-aminosalicylic acid: A preliminary study

AU - Mantena, S.K.

AU - Unnikrishnan, M.K.

AU - Chandrasekharan, K.

N1 - Cited By :4 Export Date: 10 November 2017 CODEN: JEPOE Correspondence Address: Unnikrishnan, M. K.; Department of Pharmacology, College of Pharmaceutical Sciences, Manipal-576 119, India; email: mkunnikrishnan@gmail.com Chemicals/CAS: mesalazine, 89-57-6; Aminosalicylic Acids; Copper, 7440-50-8; Radiation-Protective Agents; Zinc, 7440-66-6 Manufacturers: Sigma, United States References: Barcellos-Hoff, M.H., Park, C., Wright, E.G., Radiation and the microenvironment - tumorigenesis and therapy (2005) Nature Rev Cancer, 58, pp. 867-875; Sonntag, V.C., (1987) The chemical basis of radiation biology, , London: Taylor and Francis;; Joshi, R., Kumar, S., Unnikrishnan, M., Mukherjee, T., Free radical scavenging reactions of sulfasalazine, 5-aminosalicylic acid and sulfapyridine: Mechanistic aspects and antioxidant activity (2005) Free Radic Res, 39, pp. 1163-1172; Sudheer Kumar, M., Unnikrishnan, M.K., Uma Devi, P., Effect of 5-aminosalicylic acid on radiation-induced micronuclei in mouse bone marrow (2003) Mutat Res, 527, pp. 7-14; Unnikrishnan, M.K., Sudheer Kumar, M., Devi, U., Joshi, R., Radha, V., Mukherjee, T., 5-aminosalicylic acid and sulfasalazine reduces gamma radiation-induced oxidative stress: Involvement of p53/p21 pathway (2005) Free Radic Biol Med, 39 (SUPPL. 1), pp. S119; Kiremit-Korkut, N., Korkut, C., Bilge, H., Protective effect of mesalamine against oxidative injury in a rat model of radiation rectitis (2004) Curr Ther Res, 65, pp. 433-442; Fridovich, I., Superoxide dismutases (1986) Adv. Enzymol. Relat. Areas Mol. Biol, 58, pp. 61-97; Gee, C.A., Kittridge, K.J., Willson, R.L., Peroxy free radicals, enzymes and radiation damage: Sensitisation by oxygen and protection by superoxide dismutase and antioxidants (1985) Br J Radiol, 58, pp. 251-256; Omar, B.A., Flores, S.C., Mc Cord, J.M., Superoxide dismutase: Pharmacological developments and applications (1992) Adv Pharmacol, 23, pp. 109-161; Sorenson, J.R.J., Soderberg, L.S., Chang, L.W., Radiation protection and radiation recovery with essential metalloelement chelates (1995) Proc Soc Exp Biol Med, 210, pp. 191-204; Czapski, G., Goldstein, S., Requirements for SOD mimics operating in vitro to work also in vivo (1991) Free Radic Res Comm, pp. 12-13,167-171; Riley, D.P., Functional mimics of superoxide dismutase enzymes as therapeutic agents (1999) Chem Rev, 99, pp. 2573-2587; Koiram, P.R., Veerapur, V.P., Kunwar, A., Mishra, B., Barik, A., Priyadarsini, I.K., Mazhuvancherry, U.K., Effect of curcumin and curcumin copper complex (1:1) on radiation-induced changes of anti-oxidant enzymes levels in the livers of Swiss albino mice (2007) J Radiat Res, 48, pp. 241-245; Sorenson, J.R.J., Cu, F., Mn, and Zn chelates offer a medicinal chemistry approach to overcoming radiation injury (2002) Curr Med Chem, 9, pp. 639-662; Sorenson, J.R.J., Copper chelates as possible active forms of the antiarthritic agents (1976) J Med Chem, 19, pp. 135-148; Ganasoundari, A., Uma Devi, P., Rao, M.N.A., Protection against radiation-induced chromosome damage in mouse bone marrow by ocimum sanctum (1997) Mutat Res, 373, pp. 271-276; Sorensen, K.J., Zetterberg, L.A., Nelson, D.O., Grawe, J., Tucker, J.D., The in vivo dose rate effect of chronic gamma radiation in mice: Translocation and micronucleus analyses (2000) Mutat Res, 457, pp. 125-136; Joksic, G., Petrovic, S., Ilic, Z., Age-related changes in radiation-induced micronuclei among healthy adults (2004) Brazilian J Medical Biol Res, 37, pp. 1111-1117; Schmitz, A., Bayer, J., Dechamps, N., Thomas, G., Intrinsic susceptibility to radiation-induced apoptosis of human lymphocyte subpopulations (2003) Int J Radiat Oncol Biol Phys, 57, pp. 769-778; Scott, D., Spreadborough, A.R., Roberts, S.A., Less G2 arrest in irradiated cells of breast cancer patients than in female controls: A contribution to their enhanced chromosomal radiosensitivity? (2003) Int J Radiat Biol, 79, pp. 405-411; Uma Devi, P., Ganasoundari, A., Vrinda, B., Srinivasan, K.K., Unnikrishnan, M.K., Radiation protection by the ocimum flavonoids orientin and vicenin: Mechanisms of action (2000) Radiat Res, 154, pp. 455-460; Prabhakar, K.R., Veerapur, V.P., Parihar, K.V., Priyadarsini, K.I., Rao, B.S., Unnikrishnan, M.K., Evaluation and optimization of radioprotective activity of coronopus didymus Linn. in gamma-irradiated mice (2006) Int J Radiat Biol, 82, pp. 525-536; Jagetia, G.C., Ganapathi, N.G., Effect of copperglycinate on the radiation induced micronuclei formation in mice bone marrow (1990) Radiat Environ Biophys, 29, pp. 115-118; Ghosh, M.N., (1994) Fundamentals of Experimental Pharmacology, pp. 153-157. , Calcutta: Scientific Book Agency;; Geigy JR. Documents Geigy scientific tables. London, UK: J. Board & Co. Ltd.; 1956, p. 26-48; Uma Devi, P., Ganasoundari, A., Rao, B.S.S., Srinivasan, K.K., In vivo radioprotection by ocimum flavonoids: Survival of mice (1999) Radiat Res, 151, pp. 74-78; Satyamitra, M., Uma Devi, P., Murase, H., Kagiya, V.T., In vivo postirradiation protection by a vitamin E analog, alpha-TMG (2003) Radiat Res, 160, pp. 655-661; Uma Devi, P., Prasanna, P.G.S., Comparative radioprotection of mouse haemopoetic study by some thiols and a polysaccharide (1995) Proc Natl Acad Sci Lett, 65, pp. 1-4; Jagetia, G.C., Baliga, M.S., Modulation of antineoplastic activity of cyclophosphamide by Alstonia scholaris in the Ehrlich ascites carcinoma-bearing mice (2003) J Exp Ther Oncol, 3, pp. 272-282; Coleman, C.N., Blakely, W.F., Fike, J.R., Mac Vitte, T.J., Metting, N.F., Mitchell, J.B., Moulder, J.E., Wong, R.S.L., Molecular and cellular biology of moderate-dose (1-10 Gy) radiation and potential mechanisms of radiation protection: Report of a workshop at Bethesda, Maryland, December 17-18, 2001 (2003) Radiat Res, 159, pp. 12-834; Matsubara, J., Tajima, Y., Karasawa, M., Promotion of radioresistance by metallothionine induction prior to irradiation (1981) Environ Res, 35, pp. 66-74; Henderson, T.D., Burt, R.L., Kaufman, S.E., Willingham, W.M., Sorenson, J.R.J., Radiorecovery activity of manganese (III)2(II)(U3-0)(U-3,5- diisopropylsalicylate)6 (1993) Radiat Res, 136, pp. 126-129; Floersheim, G.L., Bieri, A., Further studies on selective radioprotection by organic zinc salt and synergism of zinc aspartate with WR (1990) Br J Radiol, 63, pp. 468-475; Soderberg, L.S., Barnett, J.B., Baker, M.L., Salari, H., Sorenson, J.R.J., Copper(II)(3,5-diisopropylsalicylate) 2 accelerates recovery of B and T cell reactivity following irradiation (1987) Scand. J. Immunol, 26, pp. 495-502; Soderberg, L.S., Barnett, J.B., Baker, M.L., Salari, H., Sorenson, J.R.J., Copper(II)2(3,5-diisopropylsalicylate)4 stimulates hemopoiesis in normal and irradiated mice (1988) Exp Hematol, 16, pp. 577-580; Soderberg, L.S., Barnett, J.B., Baker, M.L., Salari, H., Sorenson, J.R.J., Post irradiation treatment with copper(II)2(3,5-diisopropylsalicylate) 4 enhances radiation recovery and hemopoietic regeneration (1990) Exp Hematol, 18, pp. 801-805; Floersheim, G.L., Chiodetti, N., Bieri, A., Differential radioprotection of bone marrow and tumour cells by zinc aspartate (1988) Br J Radiol, 61, pp. 501-508; Roy, M.B., Mandal, P.C., Bhattacharyya, S.N., Radiosensitization of thymine by copper(II) and nickel(II) complexes of metronidazole (1996) Int J Radiat Biol, 69, pp. 471-480; Savoye, C., Sabattier, R., Charlier, M., Spotheim, M.M., Sequence-modulated radiosensitization of DNA by copper ions (1996) Int J Radiat Biol, 70, pp. 189-198; Har-El, R., Chevion, M., Zinc(II) protects against metal-mediated free radical induced damage: Studies on single and double-strand DNA breakage (1991) Free Radic Res Commun, 2, pp. 509-515

PY - 2008

Y1 - 2008

N2 - The effect of copper and zinc complexes of 5-aminosalicylic acid (hereafter referred to as Cu-5ASA and Zn-5ASA, respectively) against whole-body gamma radiation-induced cytotoxicity was studied in Swiss albino mice. Protection against lethal irradiation was evaluated from 30 day mouse survival (10 Gy) and endogenous spleen colony assay (11 Gy); and against sublethal dose (4 Gy) was assessed from gamma irradiation (RT)-induced formation of micronuclei in the mouse bone marrow 24 h postirradiation. Pretreatment with either Cu-5ASA (2.5-9 mg/kg) or Zn-5ASA (3.5-14 mg/kg) intraperitoneally (i.p.) delayed and reduced percentage mortality in mice exposed to 10 Gy RT. The doses 9 mg/kg for Cu-5ASA and 7 mg/kg for Zn-5ASA were found to be the most effective dose in preventing RT-induced weight loss and reducing percentage mortality. Both the drugs also caused an increase in the endogenous spleen colonies in mouse exposed to 11 Gy RT. At sublethal doses of RT, pretreatment with either Cu-5ASA or Zn-5ASA resulted in a significant decrease in the RT-induced micronucleated polychromatic erythrocytes and normochromatic erythrocytes (MPCEs and MNCEs) and an increase in the ratio of PCE to NCE (P/N), at 24 h postirradiation. These results show that both Cu-5ASA and Zn-5ASA are effective in protecting normal tissues against lethal and sublethal doses of RT. Further pretreatment with either Cu-5ASA or Zn-5ASA enhanced the survival of tumor-bearing mice (Ehrlich's ascites carcinoma) exposed to 7.5 Gy RT. In fact, both the complexes caused an increase in the mean and average survival times (MST and AST) when compared to the irradiated control, suggesting a synergetic effect of these drugs with radiation in causing cytotoxicity to the tumor cells. The data clearly indicate that both Cu-5ASA and Zn-5ASA significantly reduced the deleterious effect of radiation and hence could be useful agents in reducing the side effects of therapeutic radiation. © 2008 by Begell House, Inc.

AB - The effect of copper and zinc complexes of 5-aminosalicylic acid (hereafter referred to as Cu-5ASA and Zn-5ASA, respectively) against whole-body gamma radiation-induced cytotoxicity was studied in Swiss albino mice. Protection against lethal irradiation was evaluated from 30 day mouse survival (10 Gy) and endogenous spleen colony assay (11 Gy); and against sublethal dose (4 Gy) was assessed from gamma irradiation (RT)-induced formation of micronuclei in the mouse bone marrow 24 h postirradiation. Pretreatment with either Cu-5ASA (2.5-9 mg/kg) or Zn-5ASA (3.5-14 mg/kg) intraperitoneally (i.p.) delayed and reduced percentage mortality in mice exposed to 10 Gy RT. The doses 9 mg/kg for Cu-5ASA and 7 mg/kg for Zn-5ASA were found to be the most effective dose in preventing RT-induced weight loss and reducing percentage mortality. Both the drugs also caused an increase in the endogenous spleen colonies in mouse exposed to 11 Gy RT. At sublethal doses of RT, pretreatment with either Cu-5ASA or Zn-5ASA resulted in a significant decrease in the RT-induced micronucleated polychromatic erythrocytes and normochromatic erythrocytes (MPCEs and MNCEs) and an increase in the ratio of PCE to NCE (P/N), at 24 h postirradiation. These results show that both Cu-5ASA and Zn-5ASA are effective in protecting normal tissues against lethal and sublethal doses of RT. Further pretreatment with either Cu-5ASA or Zn-5ASA enhanced the survival of tumor-bearing mice (Ehrlich's ascites carcinoma) exposed to 7.5 Gy RT. In fact, both the complexes caused an increase in the mean and average survival times (MST and AST) when compared to the irradiated control, suggesting a synergetic effect of these drugs with radiation in causing cytotoxicity to the tumor cells. The data clearly indicate that both Cu-5ASA and Zn-5ASA significantly reduced the deleterious effect of radiation and hence could be useful agents in reducing the side effects of therapeutic radiation. © 2008 by Begell House, Inc.

M3 - Article

VL - 27

SP - 123

EP - 134

JO - Journal of Environmental Pathology, Toxicology and Oncology

JF - Journal of Environmental Pathology, Toxicology and Oncology

SN - 0731-8898

IS - 2

ER -