Experimental study on protective effects of Hesperetin against intestinal ischemia–reperfusion injury in rats

Subject Areas : Journal of Comparative Pathobiology

Golkar, Sh., Mohajeri, D., Kaffash Elahi, R. . ¹ ( . )

Received: 2018-12-20 Accepted : 2018-12-20 Published : 2018-12-22

Keywords: Hesperetin, Ischemia-reperfusion, Intestine, Rat,

Abstract :

The intestinal mucosa is known to be adversely affected by ischemia-reperfusion (I/R). It has been demonstrated that Hesperetin has protective effects against ischemia-reperfusion injury on various organs. The aim of this study is to determine protective effects of Hesperetin on I/R injury of the intestine in rats. For this purpose, forty male Wistar rats were randomly divided into four groups as control (group 1), sham IR (group 2), intestinal IR (group 3) and Hesperetin plus intestinal IR (group 4). Intestinal IR was produced by 30 min of intestinal ischemia followed by a 60 min of reperfusion. Rats in the group 4 received Hesperetin (1000 U/kg) subcutaneously, 120 minutes before ischemia. After the experiments, the colon was removed and the tissues were processed for histopathological examination. Serum total antioxidant activity (TAA), and levels of Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were measured in colon tissue. Histopathology show that, severe inflammatory cell infiltration, hyperemia and hemorrhage in lamina propria, as well as epithelial cell necrosis and reduction of mucosal thickening in colon tissues of the intestinal IR group. Administration of Hesperetin alleviated the colon damage in group 4. Levels of TAA, SOD, CAT, GPx and GR decreased in the intestinal IR group, but increased significantly (p<0.05) in the IR+ Hesperetin group. Hesperetin significantly (p<0.05) decreased MDA levels which was increased by IR. The results of this study, showed that Hesperetin treatment protected the rat's intestinal tissue against intestinal ischemia-reperfusion injury.

References:

1. Abdeen, S.M., Mathew, T.C., Dashti, H.M., and Asfar, S. (2011): Protective effects of green tea on intestinal ischemia-reperfusion injury. Nutrition. 27(5): 598-603.

2. Ahlenstiel, T., Burkhardt, G., Köhler, H., Kuhlmann, M.K. (2006): Improved cold preservation of kidney tubular cells by means of adding bioflavonoids to organ preservation solutions. Transplantation. 81(2): 231-239.
3. Aranganathan S1, Nalini N. (2009): Efficacy of the potential chemopreventive agent, hesperetin (citrus flavanone), on 1,2-dimethylhydrazine induced colon carcinogenesis. Food Chem. Toxicol. 47(10): 2594-600.
4. Arul, D., Subramanian, P. (2013): Inhibitory effect of naringenin (citrus flavonone) on N-nitrosodiethylamine induced hepatocarcinogenesis in rats. Biochem. Biophys. Res. Commun. 434: 203-209.
5. Berber, I., Aydin, C., Cevahir, N., Yenisey, C., Gumrukcu, G., Kocbil, G. (2009): Tempol reduces bacterial translocation after ischemia/reperfusion injury in a rat model of superior mesenteric artery occlusion. Surg. Today. 39: 407-413.
6. Chance, B., Greenstein, D.S., Roughton, R.J.W. (1952): The mechanism of catalase action. 1. Steady-state analysis. Arch. Biochem. Biophys. 37(2): 301-321.
7. Claiborne, A. (1985): Catalase activity. In: CRC Handbook of methods for oxygen radical research, 3rd Edition (ed. Robert A.). CRC Press: Florida; 273-284.
8. Collard, C.D., Gelman, S. (2001): Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology. 94(6): 1133-1138.
9. Curtis, S.J., Mortiz, M., Sondgrass, P.J. (1972): Serum enzymes derived from liver cell fractions. I. The response to carbon tetrachloride intoxication in rats. Gastroenterology. 62(1): 84-92.
10. Fraga, C.G., Leibovitz, B.E., Tappel, A.L. (1988): Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: characterization and comparison with homogenates and microsomes. Free. Radic. Biol. Med. and Med. 4(3): 155-161.
11. Gulgun, M., Erdem, O., Ozta, E., Kesik, V., Balamtekin, N., Vurucu, S. (2010): Proanthocyanidin prevents methotrexate-induced intestinal damage and oxidative stress. Exp. Toxicol. Pathol. 62(2): 109-115.
  12. Haidari, F., Keshavarz, S.A., Rashidi, M.R., Shahi, M.M. (2009): Orange juice and hesperetin supplementation to hyperuricemic rats alter oxidative stress markers and xanthine oxidoreductase activity. J. Clin. Biochem. Nutr. 45(3): 285-291.
13. Kara, S., Gencer, B., Karaca, T., Tufan, H.A., Arikan, S., Ersan, I. (2014): Protective Effect of Hesperetin and Naringenin against Apoptosis in Ischemia/Reperfusion-Induced Retinal Injury in Rats.Sci. World. J. 14: 797-804.
14. Kinoshita, T., Lepp, Z., Kawai, Y., Terao, J., Chuman H. (2006): An integrated database of flavonoids. Biofactors. 26(3): 179-188.
15. Koike, K., Moore, F.A., Moore, E.E., Read, R.A., Carl, V.S., Banerjee, A. (1993): Gut ischemia mediates lung injury by a xanthine oxidasedependent neutrophil mechanism. J. Surg. Res. 54(5): 469-473.
16. Lee, G., Luna, H.T. (1988): Manual of histologic staining methods of the armed forces institute of pathology 3rd Edition. The Blakiston Division, Michigan. P: 32-107.
17. Mallick, J.H., Yang, W.X., Winslet, M.C., Seifalian, A.M. (2004): Ischemia–reperfusion injury of the intestine and protective strategies against injury. Dig. Dis. Sci. 49: 1359-1377.
18. Miller, N.J., Rice-Evans, C., Davies, M.J., Gopinathan, V., Milner, A. (1993): A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin. Sci. 84: 407-412.
19. Mohandas, J., Marshall, J.J., Duggin, G.G., Horvath, J.S., Tiller, D.J. (1984): Low activities of glutathione-related enzymes as factors in the genesis of urinary bladder cancer. Cancer Res. 44(11): 5086-5091.
20. Naik, S.R., Panda, V.S. (2008): Hepatoprotective effect of Ginkgoselectphytosome® in rifampicin induced liver injury in rats: Evidence of antioxidant activity. Fitoterapia. 79(6): 439-45.
21. Nalini, N., Aranganathan, S., Kabalimurthy, J. (2012): Chemopreventive efficacy of hesperetin (citrus flavonone) against 1, 2-dimethylhydrazine-induced rat colon carcinogenesis. Toxicol. Mech. Methods. 22: 397-408.
22. Nishikimi, M., Appaji, N., Yagi, K. (1972): The occurrence of superoxide anion in the reaction of reduced phenazinemethosulfate and molecular oxygen. Biochem. Biophys. Res. Commun. 46(2): 849-854.
23. Okudan, N., Belviranli, M., Gökbel, H., Oz M., Kumak A. (2013): Protective effects of curcumin supplementation on intestinal ischemia reperfusion injury.Phytomedicine. 20(10): 844-848.
24. Ozkan, O.V., Yuzbasioglu, M.F., Ciralik, H., Kurutas, E.B., Yonden Z., Aydin, M. (2009): Resveratrol, a natural antioxidant, attenuates intestinal ischemia/reperfusion injury in rats. Tohoku J. Exp. Med. 218: 251-258.
25. Pollard, S.E., Whiteman, M., Spencer, J.P.E. (2006): Modulation of peroxynitrite-induced fibroblast injury by hesperetin: a role for intracellular scavenging and modulation of ERK signalling. Biochem. Biophys. Res. Commun. 347(4): 916-923.
26. Raza SS, Khan MM, Ahmad A, Ashafaq M, Khuwaja G, Tabassum R, Javed H, Siddiqui MS, Safhi MM, Islam F. (2011): Hesperidin ameliorates functional and histological outcome and reduces neuroinflammation in experimental stroke. Brain Res. 1420: 93-105.
27. Rotruck, J.T., Pope, A.L., Ganther, H.E., Swanson, A.B., Hafeman, D.G., Hoekstra, W.G. (1973): Selenium: biochemical role as a component of glutathione peroxidase. Science. 179(73): 588-590.
28. Sener, G., Eksioglu-Demiralp, E., Cetiner, M., Ercan, F., Yegen, B.C. (2006): β glucan ameliorates methotrexate induced oxidative organ injury via its antioxidant and immunomodulatory effects. Eur. J. Pharmacol. 542: 170-178.
29. Swank, G.M., Deitch, E.A. (1996): Role of the gut in multiple organ failure: Bacterial translocation and permeability changes. World J. Surg. 20(4): 411-417.
30. Testai, L., Martelli, A., Cristofaro, M., Breschi, M.C., Calderone V. (2013): Cardioprotective effects of different flavonoids against myocardial ischaemia/reperfusion injury in Langendorff-perfused rat hearts. J. Pharm. Pharmacol. 65: 750-756.
31. Viswa, K.K., Premila, A., Bina, I. (2007): Alteration in antioxidant defense mechanisms in the small intestines of methotrexate treated rat may contribute to its gastrointestinal toxicity. J. Cancer Ther. 5: 501-510.
32. Yamamoto, S., Tanabe, M., Wakabayashi, G., Shimazu, M., Matsumoto, K., Kitajima, M. (2001): The role of tumor necrosis factor-alpha and interleukin-1 beta in ischemia–reperfusion injury of the rat small intestine. J. Surg. Res. 99: 134-141.
33. Yildiz, Y., Kose, H., Cecen, S., Ergin, K., Demir, E.M., Serter, M. (2010): Protective effect of leflunomide on intestinal ischemia–reperfusion injury: leflunomide against intestinal ischemia–reperfusion. Dig. Dis. Sci. 55: 245-252.