In vivo radioprotection by 5-aminosalicylic acid

S.K. Mantena, M.K. Unnikrishnan, R. Joshi, V. Radha, P.U. Devi, T. Mukherjee

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19 Citations (Scopus)

Abstract

The radioprotective effect of 5-aminosalicylic acid (5ASA) was investigated in mouse bone marrow. The present study was aimed at investigating the radioprotective effect of pre-irradiation treatment with 5ASA against a range of whole-body lethal (8-11 Gy) and sublethal (1-4 Gy) doses of gamma-radiation (RT) in adult Swiss albino mice. Protection against lethal irradiation was evaluated from 30-day mouse survival and against sublethal doses was assessed from chromosomal aberrations in the bone marrow 24 h after irradiation. An intraperitoneal injection of 5ASA at a dose of 25 mg/kg body weight (b. wt.) 30 min before lethal RT increased survival, giving a dose modification factor (DMF) of 1.08. Injection of 5ASA (25 mg/kg b. wt.) 60 or 30 min before or within 15 min after 3 Gy whole body RT resulted in a significant decrease in the radiation-induced aberrant metaphases, at 24 h post-irradiation. Maximum effect was seen when the drug was administered 30 min before irradiation. 5ASA (25 mg/kg b. wt.) significantly reduced the number of aberrant metaphases and the different types of aberrations at all the radiation doses (1-4 Gy) tested, giving a DMFs of 1.43 for number of aberrant metaphases. 5ASA pretreatment also significantly enhanced the endogenous spleen colonies in mouse exposed to 11 Gy RT. Pretreatment with 5ASA, protected plasmid DNA (pGEM-7Zf) against breakage induced by RT and Fenton reactants. Using nanosecond pulse radiolysis technique, the bimolecular rate constant of the reaction of 5ASA with hydroxyl radical was found to be 6.7 × 109 M-1 s-1. The p53 and p21 protein levels of bone marrow and spleen were evaluated to identify the specific molecular mechanisms. Both p53 and p21 increased 24 h after 6 Gy irradiation, while treatment with 5ASA inhibited this RT-induced increase. Therefore, the present data suggest that 5ASA pretreatment decreases death caused by RT-induced gastrointestinal and hemopoeitic syndromes. The proposed mechanism of radioprotection by 5ASA is through the inhibition of damage to DNA, lipids, and proteins; and prevention of RT-induced increased expression of p53 and p21. © 2007 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)63-79
Number of pages17
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume650
Issue number1
DOIs
Publication statusPublished - 2008

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Mesalamine
Radiation
Metaphase
Bone Marrow
Body Weight
Spleen
Pulse Radiolysis
Radiation Dosage
Whole-Body Irradiation
Gamma Rays
Intraperitoneal Injections
Chromosome Aberrations
Hydroxyl Radical
DNA Damage
Proteins
Plasmids

Cite this

Mantena, S. K., Unnikrishnan, M. K., Joshi, R., Radha, V., Devi, P. U., & Mukherjee, T. (2008). In vivo radioprotection by 5-aminosalicylic acid. Mutation Research - Genetic Toxicology and Environmental Mutagenesis, 650(1), 63-79. https://doi.org/10.1016/j.mrgentox.2007.10.005
Mantena, S.K. ; Unnikrishnan, M.K. ; Joshi, R. ; Radha, V. ; Devi, P.U. ; Mukherjee, T. / In vivo radioprotection by 5-aminosalicylic acid. In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 2008 ; Vol. 650, No. 1. pp. 63-79.
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title = "In vivo radioprotection by 5-aminosalicylic acid",
abstract = "The radioprotective effect of 5-aminosalicylic acid (5ASA) was investigated in mouse bone marrow. The present study was aimed at investigating the radioprotective effect of pre-irradiation treatment with 5ASA against a range of whole-body lethal (8-11 Gy) and sublethal (1-4 Gy) doses of gamma-radiation (RT) in adult Swiss albino mice. Protection against lethal irradiation was evaluated from 30-day mouse survival and against sublethal doses was assessed from chromosomal aberrations in the bone marrow 24 h after irradiation. An intraperitoneal injection of 5ASA at a dose of 25 mg/kg body weight (b. wt.) 30 min before lethal RT increased survival, giving a dose modification factor (DMF) of 1.08. Injection of 5ASA (25 mg/kg b. wt.) 60 or 30 min before or within 15 min after 3 Gy whole body RT resulted in a significant decrease in the radiation-induced aberrant metaphases, at 24 h post-irradiation. Maximum effect was seen when the drug was administered 30 min before irradiation. 5ASA (25 mg/kg b. wt.) significantly reduced the number of aberrant metaphases and the different types of aberrations at all the radiation doses (1-4 Gy) tested, giving a DMFs of 1.43 for number of aberrant metaphases. 5ASA pretreatment also significantly enhanced the endogenous spleen colonies in mouse exposed to 11 Gy RT. Pretreatment with 5ASA, protected plasmid DNA (pGEM-7Zf) against breakage induced by RT and Fenton reactants. Using nanosecond pulse radiolysis technique, the bimolecular rate constant of the reaction of 5ASA with hydroxyl radical was found to be 6.7 × 109 M-1 s-1. The p53 and p21 protein levels of bone marrow and spleen were evaluated to identify the specific molecular mechanisms. Both p53 and p21 increased 24 h after 6 Gy irradiation, while treatment with 5ASA inhibited this RT-induced increase. Therefore, the present data suggest that 5ASA pretreatment decreases death caused by RT-induced gastrointestinal and hemopoeitic syndromes. The proposed mechanism of radioprotection by 5ASA is through the inhibition of damage to DNA, lipids, and proteins; and prevention of RT-induced increased expression of p53 and p21. {\circledC} 2007 Elsevier B.V. All rights reserved.",
author = "S.K. Mantena and M.K. Unnikrishnan and R. Joshi and V. Radha and P.U. Devi and T. Mukherjee",
note = "Cited By :17 Export Date: 10 November 2017 CODEN: MRGMF Correspondence Address: Mantena, S.K.; Department of Pharmacology, College of Pharmaceutical Sciences, Manipal, 576119, India; email: sushdheer@yahoo.com Chemicals/CAS: mesalazine, 89-57-6; protein p21, 85306-28-1; Mesalamine, 89-57-6; Radiation-Protective Agents; Tumor Suppressor Protein p53 Manufacturers: Sigma, United Kingdom References: Barcellos-Hoff, M.H., Park, C., Wright, E.G., Radiation and the microenvironment-tumorigenesis and therapy (2005) Nat. Rev.-Cancer, 58, pp. 867-875; Sonntag, V.C., (1987) The Chemical Basis of Radiation Biology, , Taylor and Francis, London; Weiss, J.F., Kumar, K.S., Antioxidant mechanisms in radiation injury and radioprotection (1988) Cellular Antioxidant Defence Mechanisms, pp. 163-189. , Chow C.K. (Ed), CRC Press, Florida; Monig, H., Messerschmidt, O., Streffer, C., (1990) Chemical radioprotection in mammals and in man. Radiation exposure and occupational risks, pp. 97-143. , Scherer E., Streffer C., and Trott K.R. (Eds), Springer-Verlag, Berlin; Uma Devi, P., Normal tissue protection in cancer therapy: progress and prospects (1998) Acta Oncol., 37, pp. 247-252; Tannehill, S.P., Mehta, M.P., Amifostine and radiation therapy: past, present, and future (1996) Semin. Oncol., 23, pp. 69-77; DiMasi, J.A., New drug development in the United States from 1963 to 1999 (2001) Clin. Pharmacol. Ther., 69, pp. 286-296; Rhodes, J., Thomas, G., Evans, B.K., Inflammatory bowel disease management. Some thoughts on future drug developments (1997) Drugs, 3, pp. 189-194; Peskar, B.M., Dreyling, K.W., May, B., Schaarschmidt, K., Goebell, H., Possible mode of action of 5-aminosalicylic acid (1987) Dis. Dig. Sci., 32, pp. S51-S56; Miles, A.M., Grisham, M.B., Antioxidant properties of aminosalicylates (1994) Methods Enzymol., 234, pp. 555-572; Conner, E.M., Brand, S.J., Davis, J.M., Kang, D.Y., Grisham, M.B., Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease: toxins, mediators, and modulators of gene expression (1996) Inflamm. Bowel Dis., 2, pp. 133-147; Keshavarzian, A., Sedghi, S., Kanofsky, J., List, T., Robinson, C., Ibrahim, C., Winship, D., Excessive production of reactive oxygen metabolites by inflamed colon: analysis by chemiluminescence probe (1992) Gastroenterology, 103, pp. 177-185; Lih-Brody, L., Powell, S.R., Collier, K.P., Reddy, G.M., Cerchia, R., Kahn, E., Weissman, G., Mullin, G.E., Increased oxidative stress and decreased antioxidant defenses of inflammatory bowel disease (1996) Dig. Dis. Sci., 41, pp. 2078-2086; Millar, A.D., Rampton, D.S., Chander, C.L., Claxson, A.W.D., Blades, S., Coumbe, A., Panetta, J., Blake, D.R., Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis (1996) Gut, 39, pp. 407-415; Goncalves, E., Almeida, L.M., Dinis, T.C.P., Antioxidant activity of 5-aminosalicylic acid against peroxidation of phosphatidylcholine liposomes in the presence of α-tocopherol. A synergistic interaction? (1998) Free Radical Res., 29, pp. 53-66; Fischer-Nielsen, A., Poulsen, H.E., Loft, S., 8-Hydroxydeoxyguanosine in vitro: effects of glutathione, ascorbate and 5-aminosalicylic acid (1992) Free Radical Biol. Med., 13, pp. 121-126; Fischer-Nielsen, A., Jeding, I.B., Loft, S., Radiation-induced formation of 8-hydroxy-2′-deoxyguanosine and its prevention by scavengers (1994) Carcinogenesis, 15, pp. 1609-1612; Fischer-Nielsen, A., Loft, S., Jensen, K.G., Effect of ascorbate and 5-aminosalicylic acid on light-induced 8-hydroxydeoxyguanosine formation in V79 hamster cells (1993) Carcinogenesis, 14, pp. 2431-2433; Baugham, C.A., Canney, P.A., Buchanan, R.B., Pickering, R.M., A randomized trail to assess the efficiency of 5-aminosalicylic acid for prevention of radiation enteritis (1993) Clin. Oncol. (R. Coll. Radiol.), 5, pp. 19-24; Freund, U., Scholmerich, J., Siems, H., Kluge, F., Schafer, H.E., Wannenmachner, M., Unerwunschte Nebenwirkungen bie Anwendung von Mesalzine (5-aminosalicylic acid) under Strahlentherapie (1987) Strahlenther. Onkol., 163, pp. 678-680; Kilic, D., Ozenirler, S., Egenhan, I., Dursun, A., Sulfasalazine decreases acute gastrointestinal complications due to pelvic radiotherapy (2001) Ann. Pharmacother., 35, pp. 806-810; Kilic, D., Ozenirler, S., Egenhan, I., Dursun, A., Double-blinded, randomized, placebo-controlled study to evaluate the effectiveness of sulphasalazine in preventing acute gastrointestinal complications due to radiotherapy (2000) Radiother. Oncol., 57, pp. 125-129; 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; 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; 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; Ganasoundari, A., Devi, P.U., Rao, B.S., Enhancement of bone marrow radioprotection and reduction of WR-2721 toxicity by Ocimum sanctum (1998) Mutat. Res., 397, pp. 303-312; Uma Devi, P., Bisht, K.S., Vinitha, M., A comparative study of radioprotection by Ocimum flavonoids and synthetic protectors in the mouse (1998) Br. J. Radiol., 71, pp. 782-784; Savage, J.R.K., Classification and relationships of induced chromosomal structural changes (1976) J. Med. Genet., 12, pp. 103-122; Bender, M.A., Awa, A.A., Brooks, A.L., Evans, H.J., Groer, P.G., Littlefield, L.G., Pereira, C., Wachholz, B.W., Current status of cytogenetic procedures to detect and quantify previous exposures to radiation (1988) Mutat. Res., 196, pp. 103-159; Puro, E.A., Clark, G.M., The effect of exposure rate on animal lethality and spleen colony survival (1972) Radiat. Res., 52, pp. 115-129; 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, p. 1; Prasanna, P.G., Uma Devi, P., Modification of WR-2721 radiation protection from gastrointestinal injury and death in mice by 2-mercaptopropionylglycine (1993) Radiat. Res., 133, pp. 111-115; Prabhakar, K.R., Veerapur, V.P., Vipan Parihar, K., Priyadarsini, K.I., Rao, B.S.S., Unnikrishnan, M.K., Evaluation and optimization of radioprotective activity of Coronopus didymus Linn. in-irradiated mice (2006) Int. J. Radiat. Biol., 82, pp. 525-536; Midgley, C.A., Owens B, B., Briscoe, C.V., Thomas, D.B., Lane, D.P., Hall, P.A., Coupling between gamma irradiation, p53 induction and the apoptotic response depends upon cell type in vivo (1995) J. Cell Sci., 108, pp. 1843-1848; Mantena, S.K., Katiyar, S.K., Grape seed proanthocyanidins inhibit UV-radiation-induced oxidative stress and activation of MAPK and NF-kappaB signaling in human epidermal keratinocytes (2006) Free Radical Biol. Med., 40, pp. 1603-1614; Wijewickreme, A.N., Krejpcio, Z., Kitts, D.D., Hydroxyl scavenging activity of glucose, fructose and ribose-lysine model Maillard products (1999) J. Food Sci., 64, pp. 457-461; Guha, S.N., Moorthy, P.N., Kishore, K., Naik, D.B., Rao, K.N., One-electron reduction of thionine studied by pulse radiolysis (1987) Proc. Indian Acad. Sci. (Chem. Sci.), 99, pp. 261-271; Priyadarsini, K.I., Naik, D.B., Moorthy, P.N., Mittal, J.P., Energy transfer studies of coumarin dyes using electron pulse radiolysis (1991) Proceedings of the 7th Tihany Conference on Radiation Chemistry, pp. 105-107. , Dobo J., Nykis L., and Shiller R. (Eds). Budapest, Hungary; Fielden, E.M., Chemical dosimetry of pulsed electron and X-ray source in the MeV region (1982) The Study of Fast Processes and Transient Species by Electron Pulse Radiolysis, p. 59. , Baxendale J.H., and Busi R.D. (Eds), Reidel Publishing Co, London; 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; Jagetia, G.C., Reddy, T.K., Modulation of radiation-induced alteration in the antioxidant status of mice by naringin (2005) Life Sci., 77, pp. 780-794; Weiss, J.F., Landauer, M.R., Radioprotection by antioxidants (2000) Ann. N. Y. Acad. Sci., 899, pp. 44-60; Maisin, J.R., Topalova, S., Kondi-Tamba, A., Matellin, G., Radioprotection by polysaccharides (1988) Pharmacol. Ther., 39, pp. 255-259; Neta, R., Role of cytokines in radioprotection (1988) Pharmacol. Ther., 39, pp. 261-266; Kurland, J.I., Broxmeyer, H.E., Pelus, L.M., Bockman, R.S., Moore, M.A., Role for monocyte-macrophage-derived colony-stimulating factor and prostaglandin E in the positive and negative feedback control of myeloid stem cell proliferation (1978) Blood, 52, pp. 388-407; Gentile, P., Byer, D., Pelus, L.M., In vivo modulation of murine myelopoiesis following intravenous administration of prostaglandin E2 (1983) Blood, 62, pp. 1100-1107; Quastler, H., The nature of intestinal radiation death (1956) Radiat. Res., 4, p. 303; Saharan, B.R., Saini, M.R., Uma Devi, P., MPG protection against radiation sickness and weight loss and its correlation with mortality of mice after whole body gamma irradiation (1981) Strahlentherapie, 157, pp. 138-140; MacVittie, T.J., Monroy, R.L., Patchen, M.L., Souza, L.M., Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sub-lethal and lethal whole body irradiation (1990) Int. J. Radiat. Biol., 57, pp. 723-736; Uma Devi, P., Nagarathnam, A., Rao, B.S.S., (2000) Cellular Radiobiology. Introduction to Radiation Biology, , Churchill Livingstone, New Delhi pp. 79-95; Carr, K.E., Effects of radiation damage on intestinal morphology (2001) Int. Rev. Cytol., 208, pp. 1-119; Navarro, J., Obrador, E., Pellicer, J.A., Aseni, M., Vina, J., Estrela, M., Blood glutathione as an index of radiation-induced oxidative stress in mice and humans (1997) Free Radical Biol. Med., 22, pp. 1203-1207; Jones, D.P., The role of oxygen concentration in oxidative stress: hypoxic and hyperoxic models (1985) Oxidative Stress, pp. 152-196. , Sies H. (Ed), Academic Press, New York; Meister, A., Anderson, M., Glutathione, M., (1983) Ann. Rev. Biochem., 52, pp. 711-760; Modig, H.G., Revesz, L., Non-protein sulphydryl and glutathione content of Ehrlich ascites tumour cells after treatment with the radioprotectors AET, cysteamine and glutathione (1967) Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med., 13, pp. 469-477; Beno, I., Staruchova, M., Volkovova, K., Mekinova, D., Bobek, P., Jurcovicova, M., Activity of the antioxidant system in patients with idiopathic proctocolitis and the effect of 5-aminosalicylic acid (Salofalk) (1994) Bratisl Lek Listy, 95, pp. 99-102; Valentine, J.F., Mesalamine induces manganese superoxide dismutase in rat intestinal epithelial cell lines and in vivo (2001) Am. J. Physiol. Gastrointest. Liver Physiol., 281, pp. G1044-G1050; Epperly, M.W., Bray, J.A., Esocobar, P., Bigbee, W.L., Watkins, S., Greenberger, J.S., Overexpression of the human manganese superoxide dismutase (MnSOD) transgene in subclones of murine hematopoietic progenitor cell line 32D cl 3 decreases irradiation-induced apoptosis but does not alter G2/M or G1/S phase cell cycle arrest (1999) Radiat. Oncol. Invest., 7, pp. 331-342; Hirose, K., Longo, D.L., Oppenheim, J.J., Matsushima, K., Overexpression of mitochondrial manganese superoxide dismutase promotes the survival of tumor cells exposed to interleukin-1, tumor necrosis factor, selected anticancer drugs, and ionizing radiation (1993) FASEB J., 7, pp. 361-368; Sun, Y., Free radical antioxidant enzymes and carcinogenesis (1990) Free Radical Biol. Med., 8, pp. 583-599; Girotti, A.W., Photodynamic lipid peroxidation in biological systems (1990) Photochem. Photobiol., 51, pp. 497-509; Bus, J.S., Gibson, J.E., Lipid peroxidation and its role in toxicology (1979) Rev. Biochem. Toxicol., 1, pp. 125-149; Mukhtar, H., Elmets, C.A., Photocarcinogenesis: mechanisms, models and human health implications (1996) Photochem. Photobiol., 63, pp. 355-447; Pearson, D.C., Jourd'Heuil, D., Meddings, J.B., The anti-oxidant properties of 5-aminosalicylic acid (1996) Free Radical Biol. Med., 21, pp. 367-373; Buxton, G.V., Greenstock, C.L., Helman, W.P., Ross, A.B., Critical review of rate constants of hydrated electrons, hydrogen atoms and hydroxyl radicals ({radical dot}OH) in aqueous solution (1988) J. Phys. Chem., 17, pp. 513-886; O'Neill, P., Fielden, E.M., (1993) Primary Free Radical Processes in DNA. Advances in Radiation Biology, , Academic Press pp. 53-120; Maisin, J.R., Albert, C., Henry, A., Reduction of short-term radiation lethality by biological response modifiers given alone or in association with other chemical protectors (1993) Radiat. Res., 135, pp. 332-337; Michalowski, A.D., On radiation damage to normal tissue and treatment (1994) Acta Oncol., 33, pp. 139-157; Levine, A.J., p53, the cellular gatekeeper for growth and division (1997) Cell, 88, pp. 323-331; Torres, M., Al-Buhairi, M., Alsbeih, G., Induction of p53 and p21 proteins by gamma radiation in skin fibroblasts derived from breast cancer patients (2004) Int. J. Radiat. Oncol. Biol. Phys., 58, pp. 479-484; El-Deiry, W.S., Tokino, T., Velculescu, V.E., Levy, D.B., Parsons, R., Trent, J.M., Lin, D., Vogelstein, B., WAF1, a potential mediator of p53 tumor suppression (1973) Cell, 75, pp. 817-825; Hanninen, K., Kaukonen, A.M., Kankkunen, T., Hirvonen, J., Rate and extent of ion-exchange process: the effect of physico-chemical characteristics of salicylate anions (2003) J. Control Release, 91, pp. 449-463; Turrisi, A.T., Kligerman, M.M., Glover, D.J., Glick, J.H., Norfleet, L., Gramouski M, M., Experience with Phase I trials of WR-2721 preceding radiation therapy (1983) Radioprotectors and Anticarcinogens, pp. 681-694. , Nygaard O.F., and Simic M.G. (Eds), Academic Press, New York; Yuhas, J.M., Davis, M.E., Glover, D., Brown, D.Q., Ritter, M., Circumvention of the tumor membrane barrier to WR-2721 absorption by reduction of drug hydrophilicity (1982) Int. J. Radiat. Oncol. Biol. Phys., 8, pp. 519-522; Yuhas, J.M., Active versus passive absorption kinetics as the basis for selective protection of normal tissues by S-2-(3-aminopropylamino)-ethylphosphorothioic acid (1980) Cancer Res., 40, pp. 1519-1524; Pinczowski, D., Ekbom, A., Baron, J., Yuen, J., Adami, H.O., Risk factors for colorectal cancer in patients with ulcerative colitis: a case-control study (1994) Gastroenterology, 107, pp. 117-120; Brown, W.A., Farmer, K.C., Skinner, S.A., Malcontenti-Wilson, C., Misajon, A., O'Brien, P.E., 5-aminosalicyclic acid and olsalazine inhibit tumor growth in a rodent model of colorectal cancer (2000) Dig. Dis. Sci., 45, pp. 1578-1584; Andrianopoulos, G.D., Nelson, R.L., Barch, D.H., Nyhus, L.M., Sulfasalazine alters the character of dimethylhydrazine-induced colorectal carcinoma in rats (1989) Anticancer Res., 9, pp. 1725-1728; Davis, A.E., Patterson, F., Crouch, R., The effect of therapeutic drugs used in inflammatory bowel disease on the incidence and growth of colonic cancer in the dimethylhydrazine rat model (1992) Br. J. Cancer, 66, pp. 777-780; Rodenburg, R.J., Ganga, A., van Lent, P.L., van de Putte, L.B., van Venrooij, W.J., The anti-inflammatory drug sulfasalazine inhibits tumor necrosis factor alpha expression in macrophages by inducing apoptosis (2000) Arthritis Rheum., 43, pp. 1941-1950; Munkholm, P., Loftus, E.V., Reinacher-Schick, A., Kornbluth, A., Mittmann, U., Esendal, B., Prevention of colorectal cancer in inflammatory bowel disease: value of screening and 5-aminosalicylates (2006) Digestion, 73, pp. 11-19",
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Mantena, SK, Unnikrishnan, MK, Joshi, R, Radha, V, Devi, PU & Mukherjee, T 2008, 'In vivo radioprotection by 5-aminosalicylic acid', Mutation Research - Genetic Toxicology and Environmental Mutagenesis, vol. 650, no. 1, pp. 63-79. https://doi.org/10.1016/j.mrgentox.2007.10.005

In vivo radioprotection by 5-aminosalicylic acid. / Mantena, S.K.; Unnikrishnan, M.K.; Joshi, R.; Radha, V.; Devi, P.U.; Mukherjee, T.

In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 650, No. 1, 2008, p. 63-79.

Research output: Contribution to journalArticle

TY - JOUR

T1 - In vivo radioprotection by 5-aminosalicylic acid

AU - Mantena, S.K.

AU - Unnikrishnan, M.K.

AU - Joshi, R.

AU - Radha, V.

AU - Devi, P.U.

AU - Mukherjee, T.

N1 - Cited By :17 Export Date: 10 November 2017 CODEN: MRGMF Correspondence Address: Mantena, S.K.; Department of Pharmacology, College of Pharmaceutical Sciences, Manipal, 576119, India; email: sushdheer@yahoo.com Chemicals/CAS: mesalazine, 89-57-6; protein p21, 85306-28-1; Mesalamine, 89-57-6; Radiation-Protective Agents; Tumor Suppressor Protein p53 Manufacturers: Sigma, United Kingdom References: Barcellos-Hoff, M.H., Park, C., Wright, E.G., Radiation and the microenvironment-tumorigenesis and therapy (2005) Nat. Rev.-Cancer, 58, pp. 867-875; Sonntag, V.C., (1987) The Chemical Basis of Radiation Biology, , Taylor and Francis, London; Weiss, J.F., Kumar, K.S., Antioxidant mechanisms in radiation injury and radioprotection (1988) Cellular Antioxidant Defence Mechanisms, pp. 163-189. , Chow C.K. (Ed), CRC Press, Florida; Monig, H., Messerschmidt, O., Streffer, C., (1990) Chemical radioprotection in mammals and in man. Radiation exposure and occupational risks, pp. 97-143. , Scherer E., Streffer C., and Trott K.R. (Eds), Springer-Verlag, Berlin; Uma Devi, P., Normal tissue protection in cancer therapy: progress and prospects (1998) Acta Oncol., 37, pp. 247-252; Tannehill, S.P., Mehta, M.P., Amifostine and radiation therapy: past, present, and future (1996) Semin. Oncol., 23, pp. 69-77; DiMasi, J.A., New drug development in the United States from 1963 to 1999 (2001) Clin. Pharmacol. Ther., 69, pp. 286-296; Rhodes, J., Thomas, G., Evans, B.K., Inflammatory bowel disease management. Some thoughts on future drug developments (1997) Drugs, 3, pp. 189-194; Peskar, B.M., Dreyling, K.W., May, B., Schaarschmidt, K., Goebell, H., Possible mode of action of 5-aminosalicylic acid (1987) Dis. Dig. Sci., 32, pp. S51-S56; Miles, A.M., Grisham, M.B., Antioxidant properties of aminosalicylates (1994) Methods Enzymol., 234, pp. 555-572; Conner, E.M., Brand, S.J., Davis, J.M., Kang, D.Y., Grisham, M.B., Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease: toxins, mediators, and modulators of gene expression (1996) Inflamm. Bowel Dis., 2, pp. 133-147; Keshavarzian, A., Sedghi, S., Kanofsky, J., List, T., Robinson, C., Ibrahim, C., Winship, D., Excessive production of reactive oxygen metabolites by inflamed colon: analysis by chemiluminescence probe (1992) Gastroenterology, 103, pp. 177-185; Lih-Brody, L., Powell, S.R., Collier, K.P., Reddy, G.M., Cerchia, R., Kahn, E., Weissman, G., Mullin, G.E., Increased oxidative stress and decreased antioxidant defenses of inflammatory bowel disease (1996) Dig. Dis. Sci., 41, pp. 2078-2086; Millar, A.D., Rampton, D.S., Chander, C.L., Claxson, A.W.D., Blades, S., Coumbe, A., Panetta, J., Blake, D.R., Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis (1996) Gut, 39, pp. 407-415; Goncalves, E., Almeida, L.M., Dinis, T.C.P., Antioxidant activity of 5-aminosalicylic acid against peroxidation of phosphatidylcholine liposomes in the presence of α-tocopherol. A synergistic interaction? (1998) Free Radical Res., 29, pp. 53-66; Fischer-Nielsen, A., Poulsen, H.E., Loft, S., 8-Hydroxydeoxyguanosine in vitro: effects of glutathione, ascorbate and 5-aminosalicylic acid (1992) Free Radical Biol. Med., 13, pp. 121-126; Fischer-Nielsen, A., Jeding, I.B., Loft, S., Radiation-induced formation of 8-hydroxy-2′-deoxyguanosine and its prevention by scavengers (1994) Carcinogenesis, 15, pp. 1609-1612; Fischer-Nielsen, A., Loft, S., Jensen, K.G., Effect of ascorbate and 5-aminosalicylic acid on light-induced 8-hydroxydeoxyguanosine formation in V79 hamster cells (1993) Carcinogenesis, 14, pp. 2431-2433; Baugham, C.A., Canney, P.A., Buchanan, R.B., Pickering, R.M., A randomized trail to assess the efficiency of 5-aminosalicylic acid for prevention of radiation enteritis (1993) Clin. Oncol. (R. Coll. Radiol.), 5, pp. 19-24; Freund, U., Scholmerich, J., Siems, H., Kluge, F., Schafer, H.E., Wannenmachner, M., Unerwunschte Nebenwirkungen bie Anwendung von Mesalzine (5-aminosalicylic acid) under Strahlentherapie (1987) Strahlenther. Onkol., 163, pp. 678-680; Kilic, D., Ozenirler, S., Egenhan, I., Dursun, A., Sulfasalazine decreases acute gastrointestinal complications due to pelvic radiotherapy (2001) Ann. Pharmacother., 35, pp. 806-810; Kilic, D., Ozenirler, S., Egenhan, I., Dursun, A., Double-blinded, randomized, placebo-controlled study to evaluate the effectiveness of sulphasalazine in preventing acute gastrointestinal complications due to radiotherapy (2000) Radiother. Oncol., 57, pp. 125-129; 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; 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; 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; Ganasoundari, A., Devi, P.U., Rao, B.S., Enhancement of bone marrow radioprotection and reduction of WR-2721 toxicity by Ocimum sanctum (1998) Mutat. Res., 397, pp. 303-312; Uma Devi, P., Bisht, K.S., Vinitha, M., A comparative study of radioprotection by Ocimum flavonoids and synthetic protectors in the mouse (1998) Br. J. Radiol., 71, pp. 782-784; Savage, J.R.K., Classification and relationships of induced chromosomal structural changes (1976) J. Med. Genet., 12, pp. 103-122; Bender, M.A., Awa, A.A., Brooks, A.L., Evans, H.J., Groer, P.G., Littlefield, L.G., Pereira, C., Wachholz, B.W., Current status of cytogenetic procedures to detect and quantify previous exposures to radiation (1988) Mutat. Res., 196, pp. 103-159; Puro, E.A., Clark, G.M., The effect of exposure rate on animal lethality and spleen colony survival (1972) Radiat. Res., 52, pp. 115-129; 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, p. 1; Prasanna, P.G., Uma Devi, P., Modification of WR-2721 radiation protection from gastrointestinal injury and death in mice by 2-mercaptopropionylglycine (1993) Radiat. Res., 133, pp. 111-115; Prabhakar, K.R., Veerapur, V.P., Vipan Parihar, K., Priyadarsini, K.I., Rao, B.S.S., Unnikrishnan, M.K., Evaluation and optimization of radioprotective activity of Coronopus didymus Linn. in-irradiated mice (2006) Int. J. Radiat. Biol., 82, pp. 525-536; Midgley, C.A., Owens B, B., Briscoe, C.V., Thomas, D.B., Lane, D.P., Hall, P.A., Coupling between gamma irradiation, p53 induction and the apoptotic response depends upon cell type in vivo (1995) J. Cell Sci., 108, pp. 1843-1848; Mantena, S.K., Katiyar, S.K., Grape seed proanthocyanidins inhibit UV-radiation-induced oxidative stress and activation of MAPK and NF-kappaB signaling in human epidermal keratinocytes (2006) Free Radical Biol. Med., 40, pp. 1603-1614; Wijewickreme, A.N., Krejpcio, Z., Kitts, D.D., Hydroxyl scavenging activity of glucose, fructose and ribose-lysine model Maillard products (1999) J. Food Sci., 64, pp. 457-461; Guha, S.N., Moorthy, P.N., Kishore, K., Naik, D.B., Rao, K.N., One-electron reduction of thionine studied by pulse radiolysis (1987) Proc. Indian Acad. Sci. (Chem. Sci.), 99, pp. 261-271; Priyadarsini, K.I., Naik, D.B., Moorthy, P.N., Mittal, J.P., Energy transfer studies of coumarin dyes using electron pulse radiolysis (1991) Proceedings of the 7th Tihany Conference on Radiation Chemistry, pp. 105-107. , Dobo J., Nykis L., and Shiller R. (Eds). Budapest, Hungary; Fielden, E.M., Chemical dosimetry of pulsed electron and X-ray source in the MeV region (1982) The Study of Fast Processes and Transient Species by Electron Pulse Radiolysis, p. 59. , Baxendale J.H., and Busi R.D. (Eds), Reidel Publishing Co, London; 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; Jagetia, G.C., Reddy, T.K., Modulation of radiation-induced alteration in the antioxidant status of mice by naringin (2005) Life Sci., 77, pp. 780-794; Weiss, J.F., Landauer, M.R., Radioprotection by antioxidants (2000) Ann. N. Y. Acad. Sci., 899, pp. 44-60; Maisin, J.R., Topalova, S., Kondi-Tamba, A., Matellin, G., Radioprotection by polysaccharides (1988) Pharmacol. Ther., 39, pp. 255-259; Neta, R., Role of cytokines in radioprotection (1988) Pharmacol. Ther., 39, pp. 261-266; Kurland, J.I., Broxmeyer, H.E., Pelus, L.M., Bockman, R.S., Moore, M.A., Role for monocyte-macrophage-derived colony-stimulating factor and prostaglandin E in the positive and negative feedback control of myeloid stem cell proliferation (1978) Blood, 52, pp. 388-407; Gentile, P., Byer, D., Pelus, L.M., In vivo modulation of murine myelopoiesis following intravenous administration of prostaglandin E2 (1983) Blood, 62, pp. 1100-1107; Quastler, H., The nature of intestinal radiation death (1956) Radiat. Res., 4, p. 303; Saharan, B.R., Saini, M.R., Uma Devi, P., MPG protection against radiation sickness and weight loss and its correlation with mortality of mice after whole body gamma irradiation (1981) Strahlentherapie, 157, pp. 138-140; MacVittie, T.J., Monroy, R.L., Patchen, M.L., Souza, L.M., Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sub-lethal and lethal whole body irradiation (1990) Int. J. Radiat. Biol., 57, pp. 723-736; Uma Devi, P., Nagarathnam, A., Rao, B.S.S., (2000) Cellular Radiobiology. Introduction to Radiation Biology, , Churchill Livingstone, New Delhi pp. 79-95; Carr, K.E., Effects of radiation damage on intestinal morphology (2001) Int. Rev. Cytol., 208, pp. 1-119; Navarro, J., Obrador, E., Pellicer, J.A., Aseni, M., Vina, J., Estrela, M., Blood glutathione as an index of radiation-induced oxidative stress in mice and humans (1997) Free Radical Biol. Med., 22, pp. 1203-1207; Jones, D.P., The role of oxygen concentration in oxidative stress: hypoxic and hyperoxic models (1985) Oxidative Stress, pp. 152-196. , Sies H. (Ed), Academic Press, New York; Meister, A., Anderson, M., Glutathione, M., (1983) Ann. Rev. Biochem., 52, pp. 711-760; Modig, H.G., Revesz, L., Non-protein sulphydryl and glutathione content of Ehrlich ascites tumour cells after treatment with the radioprotectors AET, cysteamine and glutathione (1967) Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med., 13, pp. 469-477; Beno, I., Staruchova, M., Volkovova, K., Mekinova, D., Bobek, P., Jurcovicova, M., Activity of the antioxidant system in patients with idiopathic proctocolitis and the effect of 5-aminosalicylic acid (Salofalk) (1994) Bratisl Lek Listy, 95, pp. 99-102; Valentine, J.F., Mesalamine induces manganese superoxide dismutase in rat intestinal epithelial cell lines and in vivo (2001) Am. J. Physiol. Gastrointest. Liver Physiol., 281, pp. G1044-G1050; Epperly, M.W., Bray, J.A., Esocobar, P., Bigbee, W.L., Watkins, S., Greenberger, J.S., Overexpression of the human manganese superoxide dismutase (MnSOD) transgene in subclones of murine hematopoietic progenitor cell line 32D cl 3 decreases irradiation-induced apoptosis but does not alter G2/M or G1/S phase cell cycle arrest (1999) Radiat. Oncol. Invest., 7, pp. 331-342; Hirose, K., Longo, D.L., Oppenheim, J.J., Matsushima, K., Overexpression of mitochondrial manganese superoxide dismutase promotes the survival of tumor cells exposed to interleukin-1, tumor necrosis factor, selected anticancer drugs, and ionizing radiation (1993) FASEB J., 7, pp. 361-368; Sun, Y., Free radical antioxidant enzymes and carcinogenesis (1990) Free Radical Biol. Med., 8, pp. 583-599; Girotti, A.W., Photodynamic lipid peroxidation in biological systems (1990) Photochem. Photobiol., 51, pp. 497-509; Bus, J.S., Gibson, J.E., Lipid peroxidation and its role in toxicology (1979) Rev. Biochem. Toxicol., 1, pp. 125-149; Mukhtar, H., Elmets, C.A., Photocarcinogenesis: mechanisms, models and human health implications (1996) Photochem. Photobiol., 63, pp. 355-447; Pearson, D.C., Jourd'Heuil, D., Meddings, J.B., The anti-oxidant properties of 5-aminosalicylic acid (1996) Free Radical Biol. Med., 21, pp. 367-373; Buxton, G.V., Greenstock, C.L., Helman, W.P., Ross, A.B., Critical review of rate constants of hydrated electrons, hydrogen atoms and hydroxyl radicals ({radical dot}OH) in aqueous solution (1988) J. Phys. Chem., 17, pp. 513-886; O'Neill, P., Fielden, E.M., (1993) Primary Free Radical Processes in DNA. Advances in Radiation Biology, , Academic Press pp. 53-120; Maisin, J.R., Albert, C., Henry, A., Reduction of short-term radiation lethality by biological response modifiers given alone or in association with other chemical protectors (1993) Radiat. Res., 135, pp. 332-337; Michalowski, A.D., On radiation damage to normal tissue and treatment (1994) Acta Oncol., 33, pp. 139-157; Levine, A.J., p53, the cellular gatekeeper for growth and division (1997) Cell, 88, pp. 323-331; Torres, M., Al-Buhairi, M., Alsbeih, G., Induction of p53 and p21 proteins by gamma radiation in skin fibroblasts derived from breast cancer patients (2004) Int. J. Radiat. Oncol. Biol. Phys., 58, pp. 479-484; El-Deiry, W.S., Tokino, T., Velculescu, V.E., Levy, D.B., Parsons, R., Trent, J.M., Lin, D., Vogelstein, B., WAF1, a potential mediator of p53 tumor suppression (1973) Cell, 75, pp. 817-825; Hanninen, K., Kaukonen, A.M., Kankkunen, T., Hirvonen, J., Rate and extent of ion-exchange process: the effect of physico-chemical characteristics of salicylate anions (2003) J. Control Release, 91, pp. 449-463; Turrisi, A.T., Kligerman, M.M., Glover, D.J., Glick, J.H., Norfleet, L., Gramouski M, M., Experience with Phase I trials of WR-2721 preceding radiation therapy (1983) Radioprotectors and Anticarcinogens, pp. 681-694. , Nygaard O.F., and Simic M.G. (Eds), Academic Press, New York; Yuhas, J.M., Davis, M.E., Glover, D., Brown, D.Q., Ritter, M., Circumvention of the tumor membrane barrier to WR-2721 absorption by reduction of drug hydrophilicity (1982) Int. J. Radiat. Oncol. Biol. Phys., 8, pp. 519-522; Yuhas, J.M., Active versus passive absorption kinetics as the basis for selective protection of normal tissues by S-2-(3-aminopropylamino)-ethylphosphorothioic acid (1980) Cancer Res., 40, pp. 1519-1524; Pinczowski, D., Ekbom, A., Baron, J., Yuen, J., Adami, H.O., Risk factors for colorectal cancer in patients with ulcerative colitis: a case-control study (1994) Gastroenterology, 107, pp. 117-120; Brown, W.A., Farmer, K.C., Skinner, S.A., Malcontenti-Wilson, C., Misajon, A., O'Brien, P.E., 5-aminosalicyclic acid and olsalazine inhibit tumor growth in a rodent model of colorectal cancer (2000) Dig. Dis. Sci., 45, pp. 1578-1584; Andrianopoulos, G.D., Nelson, R.L., Barch, D.H., Nyhus, L.M., Sulfasalazine alters the character of dimethylhydrazine-induced colorectal carcinoma in rats (1989) Anticancer Res., 9, pp. 1725-1728; Davis, A.E., Patterson, F., Crouch, R., The effect of therapeutic drugs used in inflammatory bowel disease on the incidence and growth of colonic cancer in the dimethylhydrazine rat model (1992) Br. J. Cancer, 66, pp. 777-780; Rodenburg, R.J., Ganga, A., van Lent, P.L., van de Putte, L.B., van Venrooij, W.J., The anti-inflammatory drug sulfasalazine inhibits tumor necrosis factor alpha expression in macrophages by inducing apoptosis (2000) Arthritis Rheum., 43, pp. 1941-1950; Munkholm, P., Loftus, E.V., Reinacher-Schick, A., Kornbluth, A., Mittmann, U., Esendal, B., Prevention of colorectal cancer in inflammatory bowel disease: value of screening and 5-aminosalicylates (2006) Digestion, 73, pp. 11-19

PY - 2008

Y1 - 2008

N2 - The radioprotective effect of 5-aminosalicylic acid (5ASA) was investigated in mouse bone marrow. The present study was aimed at investigating the radioprotective effect of pre-irradiation treatment with 5ASA against a range of whole-body lethal (8-11 Gy) and sublethal (1-4 Gy) doses of gamma-radiation (RT) in adult Swiss albino mice. Protection against lethal irradiation was evaluated from 30-day mouse survival and against sublethal doses was assessed from chromosomal aberrations in the bone marrow 24 h after irradiation. An intraperitoneal injection of 5ASA at a dose of 25 mg/kg body weight (b. wt.) 30 min before lethal RT increased survival, giving a dose modification factor (DMF) of 1.08. Injection of 5ASA (25 mg/kg b. wt.) 60 or 30 min before or within 15 min after 3 Gy whole body RT resulted in a significant decrease in the radiation-induced aberrant metaphases, at 24 h post-irradiation. Maximum effect was seen when the drug was administered 30 min before irradiation. 5ASA (25 mg/kg b. wt.) significantly reduced the number of aberrant metaphases and the different types of aberrations at all the radiation doses (1-4 Gy) tested, giving a DMFs of 1.43 for number of aberrant metaphases. 5ASA pretreatment also significantly enhanced the endogenous spleen colonies in mouse exposed to 11 Gy RT. Pretreatment with 5ASA, protected plasmid DNA (pGEM-7Zf) against breakage induced by RT and Fenton reactants. Using nanosecond pulse radiolysis technique, the bimolecular rate constant of the reaction of 5ASA with hydroxyl radical was found to be 6.7 × 109 M-1 s-1. The p53 and p21 protein levels of bone marrow and spleen were evaluated to identify the specific molecular mechanisms. Both p53 and p21 increased 24 h after 6 Gy irradiation, while treatment with 5ASA inhibited this RT-induced increase. Therefore, the present data suggest that 5ASA pretreatment decreases death caused by RT-induced gastrointestinal and hemopoeitic syndromes. The proposed mechanism of radioprotection by 5ASA is through the inhibition of damage to DNA, lipids, and proteins; and prevention of RT-induced increased expression of p53 and p21. © 2007 Elsevier B.V. All rights reserved.

AB - The radioprotective effect of 5-aminosalicylic acid (5ASA) was investigated in mouse bone marrow. The present study was aimed at investigating the radioprotective effect of pre-irradiation treatment with 5ASA against a range of whole-body lethal (8-11 Gy) and sublethal (1-4 Gy) doses of gamma-radiation (RT) in adult Swiss albino mice. Protection against lethal irradiation was evaluated from 30-day mouse survival and against sublethal doses was assessed from chromosomal aberrations in the bone marrow 24 h after irradiation. An intraperitoneal injection of 5ASA at a dose of 25 mg/kg body weight (b. wt.) 30 min before lethal RT increased survival, giving a dose modification factor (DMF) of 1.08. Injection of 5ASA (25 mg/kg b. wt.) 60 or 30 min before or within 15 min after 3 Gy whole body RT resulted in a significant decrease in the radiation-induced aberrant metaphases, at 24 h post-irradiation. Maximum effect was seen when the drug was administered 30 min before irradiation. 5ASA (25 mg/kg b. wt.) significantly reduced the number of aberrant metaphases and the different types of aberrations at all the radiation doses (1-4 Gy) tested, giving a DMFs of 1.43 for number of aberrant metaphases. 5ASA pretreatment also significantly enhanced the endogenous spleen colonies in mouse exposed to 11 Gy RT. Pretreatment with 5ASA, protected plasmid DNA (pGEM-7Zf) against breakage induced by RT and Fenton reactants. Using nanosecond pulse radiolysis technique, the bimolecular rate constant of the reaction of 5ASA with hydroxyl radical was found to be 6.7 × 109 M-1 s-1. The p53 and p21 protein levels of bone marrow and spleen were evaluated to identify the specific molecular mechanisms. Both p53 and p21 increased 24 h after 6 Gy irradiation, while treatment with 5ASA inhibited this RT-induced increase. Therefore, the present data suggest that 5ASA pretreatment decreases death caused by RT-induced gastrointestinal and hemopoeitic syndromes. The proposed mechanism of radioprotection by 5ASA is through the inhibition of damage to DNA, lipids, and proteins; and prevention of RT-induced increased expression of p53 and p21. © 2007 Elsevier B.V. All rights reserved.

U2 - 10.1016/j.mrgentox.2007.10.005

DO - 10.1016/j.mrgentox.2007.10.005

M3 - Article

VL - 650

SP - 63

EP - 79

JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

SN - 1383-5718

IS - 1

ER -