The protective role of silymarin against methotrexate-induced gastrointestinal injury

DOI: 10.18805/ijar.10767    | Article Id: B-470 | Page : 401-405
Citation :- The protective role of silymarin against methotrexate-induced gastrointestinal injury .Indian Journal Of Animal Research.2017.(51):401-405

Duygu Durna Çorum and Asim Kart*

asimkart@hotmail.com
Address :

Department of Pharmacology and Toxicology, Veterinary Faculty, Mehmet Akif Ersoy University, Burdur, Turkey.

Submitted Date : 27-02-2016
Accepted Date : 9-05-2016

Abstract

The protective effect of silymarin was investigated against methotrexate-induced GI injury. Forty Swiss-Albino mice were divided into 4 groups as control (Normal saline), methotrexate (15 mg/kg), silymarin (100 mg/kg) and methotrexate+silymarin (100 mg/kg + 15 mg/kg respectively). Blood and tissue samples were collected from the animals for biochemical and pathological examinations. Plasma, intestinal and gastric tissue malondialdehyde and TSA levels in methotrexate group were significantly higher than in control whereas whole blood glutathione concentration was lower in methotraxe group than in control. Plasma, intestinal and gastric TSA levels in methotrexate group were significantly increased compared to control and methotrexate+silymarin groups. Gastric tissue of methotrexate treated mice showed degeneration, necrosis, desquamation and widespread edema. However, these alterations were less severe in methotrexate+silymarin group. In conclusion, silymarin could be of therapeutic value against methotrexate-induced GI injury.

Keywords

GI injury GSH MDA Methotrexate Sialic acid Silymarin.

References

  1. Asghar, Z. and Masood, Z. (2008). Evaluation of antioxidant properties of silymarin and its potential to inhibit peroxyl radicals in vitro. Pak J Pharm Sci 21: 249-254.
  2. Basiglio, C.L., Pozzi, E.J.S., Mottino, A.D. and Roma, M.G. (2009). Differential effects of silymarin and its active component silibinin on plasma membrane stability and hepatocellular lysis. Chem-Biol Interact 179: 297-303.
  3. Beutler, E., Duran, O. and Kelley, B.M. (1986). Improved method for the determination of blood glutathione. J Lab Clin Med 28: 882–888.
  4. Chlopcikova, A., Psotova, J., Miketova, P. and Simanek, V. (2004). Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part I. Silymarin and its flavonolignans. Phytother Res 18: 107-110.
  5. Dadhania, V.P., Tripathi, D.N., Vikram, A., Ramarao, P. and Jena, G.B. (2010). Intervention of alpha-lipoic acid ameliorates methotrexate-induced oxidative stress and genotoxicity: A study in rat intestine. Chem-Biol Interact 183: 85-97.
  6. Devrim, E., Cetin, R., Kilicoglu, B., Erguder, B.I., Avci, A. and Durak, I. (2005). Methotrexate causes oxidative stress in rat kidney tissues. Renal Failure 27: 771-773.
  7. Gazak, R., Walterova, D. and Kren, V. (2007). Silybin and silymarin - New and emerging applications in medicine. Curr Med Chem 14: 315-338.
  8. Jahovic, N., Sener, G., Cevik, H., Ersoy, Y., Arbak, S. and Yegen, B.C. (2004). Amelioration of methotrexate-induced enteritis by melatonin in rats. Cell Biochem Funct 22: 169-178.
  9. Jolivet, J., Cowan, K.H., Curt, G.A., Clendeninn, N.J. and Chabner, B.A. (1983). The Pharmacology and Clinical Use of Methotrexate. New Engl J Med 309: 1094-1104.
  10. Jubeh, T.T., Antler, S., Haupt, S., Barenholz, Y. and Rubinstein, A. (2005). Local prevention of oxidative stress in the intestinal epithelium of the rat by adhesive liposomes of superoxide dismutase and tempamine. Mol Pharmaceut 2: 2-11.
  11. Kane, D., Gogarty, M., O’Leary, J., Silva, I., Bermingham, N., Bresnihan, B. and FitzGerald, O. (2004). Reduction of synovial sublining layer inflammation and proinflammatory cytokine expression in psoriatic arthritis treated with methotrexate. Arthritis Rheum-Us 50: 3286-3295.
  12. Koksal, E., Gulcin, I., Beyza, S., Sarikaya, O. and Bursal, E. (2009). In vitro antioxidant activity of silymarin. J Enzym Inhib Med Ch 24: 395-405.
  13. Kuralay, F., Yildiz, C., Ozutemiz, O., Islekel, H., Caliskan, S., Bingol, B. and Ozkal, S. (2003). Effects of trimetazidine on acetic acid-induced colitis in female Swiss rats. J Toxicol Env Heal A 66: 169-179.
  14. Mansour, H.H., Hafez, H.F. and Fahmy, N.M. (2006). Silymarin modulates cisplatin-induced oxidative stress and hepatotoxicity in rats. J Biochem Mol Biol 39: 656-661.
  15. Miyazono, Y., Gao, F. and Horie, T. (2004). Oxidative stress contributes to methotrexate-    induced small intestinal toxicity in rats. Scand J Gastroentero 39: 1119-1127.
  16. Nagakubo, J., Tomimatsu, T., Kitajima, M., Takayama, H., Aimi, N. and Horie, T. (2001). Characteristics of transport of fluoresceinated methotrexate in rat small intestine. Life Sci 69: 739-747.
  17. Pliskova, M., Vondracek, J., Kren, V., Gazak, R., Sedmera, P., Walterova, D., Psotova, J., Simanek, V. and Machala, M. (2005). Effects of silymarin flavonolignans and synthetic silybin derivatives on estrogen and aryl hydrocarbon receptor activation. Toxicology 215: 80-89.
  18. Ramasamy, K. and Agarwal, R. (2008). Multitargeted therapy of cancer by silymarin. Cancer Lett 269: 352-362.
  19. Sener, G., Eksioglu-Demiralp, E., Cetiner, M., Ercan, F. and Yegen, B.C. (2006). beta-glucan ameliorates methotrexate-    induced oxidative organ injury via its antioxidant and immunomodulatory effects. Eur J Pharmacol 542: 170-178.
  20. Siegers, C.P., Riemann, D., Thies, E. and Younes, M. (1988). Glutathione and Gsh-Dependent Enzymes in the Gastrointestinal Mucosa of the Rat. Cancer Lett 40: 71-76.
  21. Sillanaukee, P., Ponnio, M., and Jaaskelainen, I.P. (1999a). Occurrence of sialic acids in healthy humans and different disorders. Eur J Clin Invest 29: 413-425.
  22. Sillanaukee, P., Ponnio, M. and Seppa, K. (1999b). Sialic acid: New potential marker of alcohol abuse. Alcohol Clin Exp Res 23: 1039-1043.
  23. Sydow, G. (1985). A Simplified Quick Method for Determination of Sialic-Acid in Serum. Biomed Biochim Acta 44: 1721-1723.
  24. Uslu, I., Uslu, E., Belet, A., Kologlu, E. and Altuð, T (1995). Yaþlanmanýn sialik asit metabolizmasý üzerine etkisi. Endokron. Yön. Derg 4: 23-25.
  25. Uz, E., Oktem, F., Yilmaz, H., Uzar, E. and Ozguner, F. (2005). The activities of purine-    catabolizing enzymes and the level of nitric oxide in rat kidneys subjected to methotrexate: Protective effect of caffeic acid phenethyl ester. Mol Cell Biochem 277: 165-170.
  26. Yoshioka, T., Kawada, K., Shimada, T. and Mori, M. (1979). Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood. Am J Obstet Gynecol 135: 372-376.
     

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