Mitigation of azathioprine-induced oxidative hepatic injury by the flavonoid quercetin in Wistar rats

Toxicology Mechanisms and Methods

Volumn 18, Issue 8, 2008, Pages 653-660

  Shanmugarajan, T S ^a   Prithwish, N ^a   Somasundaram, I ^a   Arunsundar, M ^a   Niladri, M ^a   Lavande, J P ^a   Ravichandiran, V ^a  

^a VELS INSTITUTE OF SCIENCE   (India)

Author keywords

Antioxidants; Azathioprine; DNA damage; Hepatotoxicity; Oxidative stress; Quercetin

Indexed keywords

ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; AZATHIOPRINE; CATALASE; GAMMA GLUTAMYLTRANSFERASE; GLUTATHIONE; GLUTATHIONE PEROXIDASE; GLUTATHIONE REDUCTASE; LACTATE DEHYDROGENASE; MALONALDEHYDE; QUERCETIN; SUPEROXIDE DISMUTASE;

ADULT ANIMAL; AGAR GEL ELECTROPHORESIS; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALKALINE PHOSPHATASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIOXIDANT ACTIVITY; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CONTROL GROUP; CONTROLLED STUDY; DNA DAMAGE; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; LACTATE DEHYDROGENASE BLOOD LEVEL; LIPID PEROXIDATION; LIVER INJURY; LIVER PROTECTION; LIVER TOXICITY; MALE; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTECTION; RAT; WISTAR RAT;

RATTUS; RATTUS NORVEGICUS;

EID: 53149151870     PISSN: 15376516     EISSN: 15376524     Source Type: Journal    
DOI: 10.1080/15376510802205791     Document Type: Article

References (83)

1. Abu-Shakra, M., and Shenfeld, Y. 2001. Azathioprine therapy for patients with systemic lupus erythematosus. Lupus 10:152-153.
2. Afanas'eve, J. B., Dorozhko, A. J., Brodskii, A.V., Kostyuk, U. A., and Potapovich, A. J. 1989. Chelating and free radical scavenging mechanism of inhibitory action of rutin quercetin in lipid peroxidation. Biochem. Pharmacol. 38:1763-1769.
3. Ahmed, S., Rahman, A., Saleem, M., Athar, M., and Sultana, S. 1999. Ellagic acid ameliorates nickel induced biochemical alterations: diminution of oxidative stress. Hum. Exp. Toxicol. 18:691-698.
4. Alice, U. L., and Geoffrey, C. F. 2001. Mechanism of azathioprine-induced injury to hepatocytes: roles of glutathione depletion and mitochondrial injury. J. Hepatol. 6:756-764.
5. Amin, A., and Hamza, A. A. 2005. Hepatoprotective effects of Hibiscus, Rosmarinus and Salvia on azathioprine-induced toxicity in rats. Life Sci. 77:266-278.
6. Bonnesen, C., Eggleston, I. M., and Hayes, J. D. 2001. Dietary indoles and isothiocyanates that are generated from cruciferous vegetables can both stimulate apoptosis and confer protection against DNA damage in human colon cell lines. Cancer Res. 61:6120-6130.
7. Borges, L. P., Brandao, R., Godoi, B., Nogueira, C. W., and Zeni, G. 2008. Oral administration of diphenyl diselenide protects against cadmium-induced liver damage in rats. Chem. Biol. Interact. 171:15-25.
8. Bors, W., Heller, W., Michel, C., and Saran, M. 1990. Flavonoids as antioxidants: determination of radical-scavenging efficiencies. Methods Enzymol. 186:343-355.
9. Chenoweth, M., and Hake, C. 1962. The smaller halogenated aliphatic hydrocarbons. Ann. Rev. Pharmacol. 2:363-398.
10. Chitra, S., Devipriya, S., and Devi, C. S. S. 2001. Modulatory effect of quercetin on azathioprine induced membrane changes in the mouse spleen. Indian J. Exp. Biol. 39:132-136.
11. Clamers, A. H., Knight, P. R., and Atkinson, M. R. 1969. 6-thiopurines as substrates and inhibitors of purine oxidases: A pathway for conversion of azathioprine into 6-thiouric acid without release of 6-mercaptopurine. Aust. J. Exp. Biol. Med. Sci. 47:263-273.
12. Connell,W. R., Kamm, M. A., Ritchie, K. J., and Lennard-Jones, J. E. 1993. Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience: Gut 34:1081-1085.
13. Coskun, O., Kanter, M., Ahmet Korkmaz, A., and Sukru Oter, S. 2005. Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and β-cell damage in rat pancreas. Pharmacol. Res. 51:117-123.
14. Csokay, B., Prajda, N., Weber, G., and Olah, E. 1997. Molecular mechanisms in the antiproliferative action of quercetin. Life Sci. 60:2157-2163.
15. Daniel, F., Cadranel, J. F., Seksik, P., Cazier, A., Duong, V. H. J. P., Ziol, M., Coutarel, P., Loison, P., Jian, R., and Marteau, P. 2005. Azathioprine induced nodular regenerative hyperplasia in IBD patients. Gastroenterol. Clin. Biol. 29:600-603.
16. Duarte, J., Galisteo, M., Ocete, M. A., Pirez-Vizca?no, F., Zarzuelo, A., and Tamargo, J. 2001. Effects of chronic quercetin treatment on hepatic oxidative status of spontaneously hypertensive rats. Mol. Cell. Biochem. 221:155-160.
17. Ellman, G. L. 1959. Tissue sulfhydryl groups. Arch. Biochem. Biophys. 17:214-226.
18. Elsing, C., Placke, J., and Thomas Herrmann, T. 2007. Alcohol binging causes peliosis hepatis during azathioprine therapy in Crohn's disease. World J. Gastroenterol. 13:4646-4648.
19. Ferry, D. R., Smith, A.,Malkhandi, J., Fyfe, D.W., De, T. P. G., Anderson, D., Baker, J., and Kerr, D. J. 1996. Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin. Cancer Res. 2:659-668.
20. Fiorani, M., DeSanctis, R., Menghinello, P., Cucchiarini, L., Cellini, B., and Dacha, M. 2001. Quercetin prevents glutathione depletion induced by dehydroascorbic acid in rabbit red blood cells. Free Radic. Res. 34:639-648.
21. Formica, J. W., and Regelson, W. 1995. Review of the biology of quercetin and related bioflavonoids. Food Chem. Toxicol. 33:1061-1080.
22. Gabor, S. 1969. A kinetic photometric method for serum γ-glutamyl transpeptidase. Clin. Chem. 15:124-136.
23. Ghosh, A., and Sil, P. C. 2007. Anti-oxidative effect of a protein from Cajanus indicus L against acetaminophen-induced hepato-nephro toxicity. J. Biochem. Mol. Biol. 40:1039-1049.
24. Hanan, M., El-Gawad, A. B. D., and Khalifa, A. E. 2001. Quercetin, coenzyme q10, and l-canavanine as protective agents against lipid peroxidation and nitric oxide generation in endotoxin-induced shock in rat brain. Pharmacol. Res. 43:257-263.
25. Heim, K. E., Tagliaferro, A. R., and Bobilya, D. J. 2002. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J. Nutr. Biochem. 13:572-584.
26. Heneghan, M. A., and McFarlane, I. G. 2002. Current and novel immunosuppressive therapy for autoimmune hepatitis. Hepatology 35:7-13.
27. Hertog, M. G., Feskens, E. J., Hollman, P. C., Katan, M. B., and Kromhout, D. 1993. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 342:1007-1011.
28. Higuchi, Y. 2004. Glutathione depletion-induced chromosomal DNA fragmentation associated with apoptosis and necrosis. J. Cell. Mol. Med. 8:455-464.
29. Hollman, P. C., Van, T. J. M.,Mengelers,M. J., de Vries, J. H., and Katan, M. B. 1997. Bioavailability of the dietary antioxidant flavonol quercetin in man. Cancer Lett. 114: 139-140.
30. Husain, S. R., Cillard, J., and Cillard, P. 1987. Hydroxyl radical scavenging activity of flavonoids. Phytochemistry 26:2489-2491.
31. Inal, M. E., and Kahraman, A. 2000. The protective effect of flavonol quercetin against ultraviolet a induced oxidative stress in rats. Toxicology 154:21-29.
32. Irvine, D. S. 1996. Glutathione as a treatment for male infertility. Rev. Reprod. 1:6-12.
33. Janbaza, K. H., Saeedb, S. A., and Gilanib, A. H. 2004. Studies on the protective effects of caffeic acid and quercetin on chemical-induced hepatotoxicity in rodents. Phytomedicine 11:424-430.
34. Kaskas, B. A., Louis, E., Hindorf, U., Schaeffeler, E., Deflandre, J., Graepler, F. K., Schmiegelow, K., Gregor, M., Zanger, U. M., Eichelbaum, M., and Schwab, M. 2003. Safe treatment of thiopurine S-methyltransferase deficient Crohn's disease patients with azathioprine. Gut 52:140-142.
35. Katzka, D. A., Saul, S. H., Jorkasky, D., Sigal, H., Reynolds, J. C., and Soloway, R. D. 1986. Azathioprine and hepatic veno-occlusive disease in renal transplant recipients. Gastroenterology 90:446-454.
36. Kawai, M., Hirano, T., Higa, S., Arimitsu, J., Maruta, M., Kuwahara, Y., Ohkawara, T., Hagihara, K., Yamadori, T., Shima, Y., Ogata, A., Kawase, I., and Tanaka, T. 2007. Flavonoids and related compounds as anti-allergic substances. Allergol. Int. 56:113-123.
37. Kim, H., Jeong, K., and Jung, S. 2006. Molecular dynamics simulations on the coplanarity of quercetin backbone for the antioxidant activity of quercetin-3-monoglycoside. Bull. Korean Chem. Soc. 27:325-328.
38. Kim, H. P., Son, K. H., Chang, H. W., and Kang, S. S. 2004. Antiinflammatory plant flavonoids and cellular action mechanisms. J. Pharmacol. Sci. 96:229-245.
39. Kim, K. A., Lee, W. K., Kim, J. K., Seo, M. S., Lim, Y., Lee, K. H., Chae, G., Lee, S. H., and Chung, Y. 2001. Mechanism of refractory ceramic bre- and rock wool induced cytotoxicity in alveolar macrophages. Arch. Occup. Environ. Health 74:9-15.
40. Kind, P. R. N., and King, E. J. 1954. Estimation of plasma phosphatase by determination of hydrolysed phenol with amino-antipyrine. J. Clin. Pathol. 7:322-326.
41. King, J. 1965. The dehydrogenases or oxidoreductases-lactacte dehydrogenase. In: Van, D. (Ed.), Practical Clinical Enzymology, Nostrand Company Limited, London, p. 83-93.
42. Korkina, L. G., and Afanas'ev, I. B. 1997. Antioxidant and chelating properties of flavonoids. Adv. Pharmacol. 38:151-163.
43. Kunz, R., and Neumayer, H. H. 1997. Maintenance therapy with triple versus double immunosuppressive regimen in renal transplantation: a meta-analysis. Transplantation 63:386-392.
44. Kuo, S.-M. 1997. Dietary flavonoid and cancer prevention: evisence and potential mechanism. Crit. Rev. Oncog. 8:47-69.
45. Lee, D. H., and Jacobs, D. R. 2005. Association between serum gamma glutamyltransferase and C-reactive protein. Atherosclerosis 178:327-330.
46. Leibovitz, B. E., and Siegel, B. V. 1980. Aspects of free radical reactions in biological systems: aging. J. Gerontol. 35:45-56.
47. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193:265-275.
48. Marklund, S., and Marklund, G. 1997. Involvement of superoxide anion radical in the autooxidation of pyrogallol and a convenient assay of superoxide dismutase. Eur. J. Biochem. 47:469-474.
49. Martin, M. J., Motilva, V., and Lastra, A. D. L. 1993. Quercetin and naringenin; effects on ulcer formation and gastric secretion in rats. Phytother. Res. 7:150-153.
50. Mates, M. 2000. Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology. Toxicology 153:83-104.
51. Middleton, E., Kandaswami, C., and Theoharides, T. C. 2000. The effects of flavonoids on mammalian cells: implications for inflammation, heart disease and cancer. Pharmacol. Rev. 52:673-751.
52. Molina, M. F., Sanchez-Reus, I., Iglesias, I., and Benedi, J. 2003. Quercetin, a flavonoid antioxidant, prevents and protects against ethanol-induced oxidative stress in mouse Liver. Biol. Pharm. Bull. 26:1398-1402.
53. Morand, C., Crespy, V., Manach, C., Besson, C., Demign'e, C., and R'em'esy, C. 1998. Plasma metabolites of quercetin and their antioxidant properties. Am. J. Physiol. 275:212-219.
54. Morel, I., Lescoat, G., Cogrel, P., Sergent, O., Pasdeloup, N., Brissot, P., Cillard, P., and Cillard, J. 1993. Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem. Pharmacol. 45:13-19.
55. Muthukumaran, S., Sudheer, A. R., Menon, V. P., and Nalini, N. 2008. Protective effect of quercetin on nicotine-induced prooxidant and antioxidant imbalance and DNA damage in Wistar rats. Toxicology 243:207-215.
56. Nagafuchi, K., and Miyazaki, K. 1991. Modulation of genotoxicity of azathioprine by intracellular glutathione in hepatocytes. J. Cancer Res. Clin. Oncol. 117:321-325.
57. Naganuma, A., Anerson, M. E., and Meister, A. 1990. Cellular glutathione as a determinant of sensitivity tomercuric chlorine toxicity. Biochem. Pharmacol. 40:693-697.
58. Navasumrit, P., Ward, T. H., Dodd, N. J., and O'Connor, P. J. 2000. Ethanol-induced free radicals and hepatic DNA strand breaks are prevented in vivo by antioxidants: effects of acute and chronic ethanol exposure. Carcinogenesis 21:93-99.
59. Ohkawa, H., Ohishi, N., and Nagi, K. 1979. Assay of lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal. Biochem. 95:351-358.
60. Opelz, G. 1995. Influence of treatment with cyclosporine, azathioprine and steroids on chronic allograft failure. The Collaborative Transplant Study. Kidney Int. 52:89-92.
61. Puglia, C. D., and Powell, S. R. 1984. Inhibition of cellular antioxidants: a possible mechanism of toxic cell injury. Environ. Health Perspect. 57:307-311.
62. Rana, S. V. S., Allen, T., and Singh, R. 2002. Inevitable glutathione, then and now. Indian J. Exp. Biol. 40:706-716.
63. Raza, M., Ahmad, M., Gado, A., and Al-shabanah, O. 2003. A comparison of hepatoprotective activities of amino guanidine and N-acetylcysteine in rat against the toxic damage induced by azathioprine. Compa. Biochem. Physiol. 134:451-456.
64. Reitman, S., and Frankel, S. 1957. Colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transminases. Am. J. Clin. Pathol. 28:56-63.
65. Rice-Evans, C., Miller, N. J., and Paganga, G. 1997. Antioxidant properties of phenolic compounds. Trends Plant Sci. 2:152-159.
66. Robak, J., and Gryglewski, R. J. 1998. Flavonoids are scavengers of superoxide anions. Biochem. Pharmacol. 37:837-841.
67. Rotruck, J. T., Pope, A. L., Ganther, H. E., Swanson, A. B., Hafeman, D. G., and Hoekstra, W. G. 1973. Selenium: biochemical roles as components of glutathione peroxidase. Science 179:588-590.
68. Russmann, S., Zimmermann, A., Krahenbuhl, S., Kern, B., and Reichen, J. 2001. Venoocclusive disease, nodular regenerative hyperplasia and hepatocellular carcinoma after azathioprine treatment in a patient with ulcerative colitis. Eur. J. Gastroenterol. Hepatol. 13:287-290.
69. Sallie, R., Tredger, J., andWilliam, R. 1991. Drugs and the liver. Biopharm. Drug Dispos. 12:251-259.
70. Sen, C. K. 1997. Nutritional biochemistry of cellular glutathione. J. Nutr. Biochem. 8:660-672.
71. Senthilkumar, S., Devaki, T., Manohar, B. M., and Babu, M. S. 2006. Effect of squalene on cyclophosphamide-induced toxicity. Clin. Chim. Acta 364:335-342.
72. Sinet, P. M., and Garba, P. 1981. Inactivation of the human Cu Zn SOD during exposure to O2 and H2O2. Arch. Biochem. Biophys. 212:411-416.
73. Singh, D., Chander, V., and Chopra, K. 2004. The effect of quercetin, a bioflavonoid on ischemia/reperfusion induced renal injury in rats. Arch. Med. Res. 35:484-494.
74. Sinha, A. K. 1972. Colorimetric assay of catalase. Anal. Biochem. 47:389-394.
75. Smith, I. K., Vierheller, T. L., and Thorne, C. A. 1988. Assay of glutathione reductase in crude tissue homogenates using 5,5′-dithiobis (2-nitrobenzoic acid). Anal. Biochem. 175:408-413.
76. Sterneck, M., Wiesner, R., Ascher, N., Roberts, J., Ferrell, L., Ludwig, J., and Lake, J. 1991. Azathioprine hepatotoxicity after liver transplantation. Hepatology 14:806-810.
77. Thampi, H. B. S., Manoj, G., Leelamma, S., and Menon, V. P. 1991. Dietary fiber and lipid peroxidation: effect of dietary fiber on levels of lipids and lipid peroxides in high fat diet. Ind. J. Exp. Biol. 29:563-567.
78. Uhlig, S., and Wendel, A. 1992. The physiological consequences of glutathione variations. Life Sci. 51:1083-1094.
79. Vernier-Massouille, G., Cosnes, J., Lemann, M., Marteau, P., Reinisch, W., Laharie, D., Cadiot, G., Bouhnik, Y., Vos, M. D., Boureille, A., Duclos, B., Seksik, P., Mary, J.-Y., and Colombel, J.-F. 2007. Nodular regenerative hyperplasia in patients with inflammatory bowel disease treated with azathioprine. Gut 56:1404-1409.
80. Vijayakumar, M., Govindarajan, R., Rao, G. M. M., Rao, C. V., Shirwaikar, A., Mehrotra, S., and Pushpangadan, P. 2006. Action of Hygrophila auriculata against streptozotocin-induced oxidative stress. J. Ethnopharmacol. 104:356-361.
81. Webster, R. P., Gawde, M. D., and Bhattacharya, R. K. 1996. Protective effect of rutin, a flavonol glycoside, on the carcinogen-induced DNA damage and repair enzymes in rats. Cancer Lett. 109:185-191.
82. Whisnant, J. K., and Pelkey, J. 1982. Rheumatoid arthritis: treatment with azathioprine (IMURAN (R)). Clinical sideeffects and laboratory abnormalities. Ann. Rheum. Dis. 41:44-47.
83. Yoshida, M., Sakai, T., Hosokawa, N., Marui, N., Matsumoto, K., Fujioka, A., Nishino, H., and Aoike, A. 1990. The effect of quercetin on cell cycle progression and growth of human gastric cancer cells. FEBS Lett. 260:10-13.