مطالعه اثرات پیشگیرانه نارینژنین از آسیب ایسکمی-خون‌رسانی مجدد روده کوچک در موش صحرایی
محورهای موضوعی :
آسیب شناسی درمانگاهی دامپزشکی
غفور موسوی
1
(
استادیار گروه علوم درمانگاهی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز، ایران.
)
تاریخ دریافت : 1393/12/05
تاریخ پذیرش : 1394/02/30
تاریخ انتشار : 1393/12/01
کلید واژه:
موش صحرایی,
روده,
ایسکمی-خون‌رسانی مجدد,
نارینژنین,
چکیده مقاله :
مخاط روده به شدت توسط ایسکمی-خون رسانی مجدد (IR) تحت تاثیر قرار می گیرد. نشان داده شده است که نارینژنین در برابر آسیب ایسکمی-خون رسانی مجدد در ارگان های مختلف دارای اثرات محافظتی می باشد. هدف از این مطالعه این است که آیا نارینژنین در آسیب ایسکمی-خون رسانی مجدد روده موش صحرایی نقش محافظتی دارد. بدین منظور، 40 سر موش صحرایی نر ویستار به طور تصادفی به چهار گروه شاهد (گروه 1)، شاهد جراحی (گروه 2)، ایسکمی-خون رسانی مجدد (گروه 3) و ایسکمی-خون رسانی مجدد به علاوه تیمار با نارینژنین (گروه 4) تقسیم شدند. آسیب ایسکمی-خون رسانی مجدد با 30 دقیقه ایسکمی روده و 60 دقیقه خون رسانی مجدد ایجاد شد. موش های گروه 4 نارینژنین (mg/kg 20) را 120 دقیقه قبل از القاء ایسکمی از طریق تزریق داخل صفاقی دریافت کردند. پس از انجام آزمایشات، ژوژنوم خارج و جهت آسیب شناسی بافتی آماده گردید. فعالیت تام آنتی اکسیدانی سرم و مقادیر مالون دی آلدئید، سوپراکسید دیسموتاز، کاتالاز، گلوتاتیون پراکسیداز و گلوتاتیون ردوکتاز در بافت ژوژنوم اندازه گیری شد. آسیب‌شناسی بافتی، ارتشاح شدید سلول های آماسی، کوتاه و کُند شدگی پرزها، خونریزی لامینا پروپریا و نکروز سلول های بافت پوششی ژوژنوم را در گروه ایسکمی-خون رسانی مجدد نشان داد. مصرف نارینژنین آسیب ژوژنوم را موش های گروه 4 کاهش داد. فعالیت تام آنتی اکسیدانی سرم و مقادیر سوپراکسید دیسموتاز، کاتالاز، گلوتاتیون پراکسیداز و گلوتاتیون ردوکتاز در گروه ایسکمی-خون رسانی مجدد کاهش یافت ولی به طور معنی داری (05/0>p) در گروه ایسکمی-خون رسانی مجدد به علاوه تیمار با نارینژنین افزایش یافت. نارینژنین مقدار مالون دی آلدئید را که در اثر ایسکمی-خون رسانی مجدد افزایش یافته بود به طور معنی داری (05/0>p) کاهش داد. نتایج ما نشان داد نارینژنین روده باریک موش های صحرایی را از آسیب ایسکمی-خون رسانی مجدد محافظت کرد.
چکیده انگلیسی:
The intestinal mucosa is known to be adversely affected by ischemia-reperfusion (I/R). It has been demonstrated that Naringenin has protective effects against ischemia-reperfusion injury in various organs. The aim of this study is to determine whether Naringenin has any protective role in 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 (group 3) and Naringenin plus intestinal IR (group 4). Intestinal IR was produced by 30 minutes of intestinal ischemia followed by a 60 minutes of reperfusion. Rats in group 4 received Naringenin (20 mg/kg) intraperitoneally, 120 minutes before ischemia. After the experiments, the jejunum 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 jejunal tissue. Histopathologically, jejunal tissues of the intestinal IR group showed severe inflammatory cell infiltration, villus shortening and blunting and hemorrhage in lamina propria, as well as epithelial cell necrosis. Administration of Naringenin alleviated the jejunal 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+Naringenin group. Naringenin significantly (p<0.05) decreased MDA levels which was increased by IR. Our results showed that Naringenin treatment protected the rat's intestinal tissue against intestinal ischemia-reperfusion injury.
منابع و مأخذ:
· 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.
· Ahlenstiel, T., Burkhardt, G., Köhler, H. and 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.
· Arul, D. and Subramanian, P. (2013). Inhibitory effect of naringenin (citrus flavonone) on N-nitrosodiethylamine induced hepatocarcinogenesis in rats. Biochemical and Biophysical Research Communications, 434: 203-209.
· Asfar, S., Zhong, R. and Grant, D. (1994). Small bowel transplantation. Surgical Clinics of North America, 74: 1197-1210.
· Berber, I., Aydin, C., Cevahir, N., Yenisey, C., Gumrukcu, G., Kocbil, G., et al. (2009). Tempol reduces bacterial translocation after ischemia/reperfusion injury in a rat model of superior mesenteric artery occlusion. Surgery Today, 39: 407-413.
· Chance, B., Greenstein, D.S. and Roughton, R.J.W. (1952). The mechanism of catalase action. 1. Steady-state analysis. Archives of Biochemistry and Biophysics, 37(2): 301-321.
· Chen, C.F., Hsueh, C.W., Tang, T.S., Wang, D., Shen, C.Y. and Pei, J.S. (2007). Reperfusion liver injury-induced superoxide dismutase and catalase expressions and protective effect of N-acetyl cysteine. Transplantation Proceedings, 39: 858-860.
· Chiou, G.C.Y. and Xu, X. (2004). Effects of some natural flavonoids on retinal function recovery after ischemic insult in the rat. Journal of Ocular Pharmacology and Therapeutics, 20(2): 107-113.
· Choi, E.J. and Ahn, W.S. (2008). Neuroprotective effects of chronic hesperetin administration in mice. Archives of Pharmacal Research, 31(11): 1457-1462.
· Cicales, L., Sileri, P., Green, M., Abu-Elmagd, K., Kocoshis, S. and Reyes, J. (2001). Bacterial translocation in clinical transplantation. Transplantation, 71: 1414-1417.
· Claiborne, A. (1985). Catalase activity In: Boca Raton FL, editor. CRC Handbook of methods for oxygen radical research. Florida: CRC Press, Boca Raton, pp: 283-284.
· Collard, C.D. and Gelman, S. (2001). Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology, 94(6): 1133-1138.
Curtis, S.J., Mortiz, M. and Sondgrass, P.J. (1972). Serum enzymes derived from liver cell fractions. I. The response to carbon tetrachloride intoxication in rats. Gastroentrology, 62(1): 84-92.
· Dembinski, A., Warzecha, Z., Konturek, S.J., Ceranowicz, P., Dembinski, M., Pawlik, W.W., et al. (2004). Extract of grapefruit-seed reduces acute pancreatitis induced by ischemia/reperfusion in rats; possible implication of tissue antioxidants. Journal of Physiology and Pharmacology, 55(4): 811-821.
· Fraga, C.G., Leibovitz, B.E. and Tappel, A.L. (1988). Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: characterization and comparison with homogenates and microsomes. Free Radical Biology and Medicine, 4(3): 155-161.
· Gulgun, M., Erdem, O., Ozta, E., Kesik, V., Balamtekin, N., Vurucu, S., et al. (2010): Proanthocyanidin prevents methotrexate-induced intestinal damage and oxidative stress. Experimental and Toxicologic Pathology, 62(2): 109-115.
· Haidari, F., Keshavarz, S.A., Rashidi, M.R., and Shahi, M.M. (2009). Orange juice and hesperetin supplementation to hyperuricemic rats alter oxidative stress markers and xanthine oxidoreductase activity. Journal of Clinical Biochemistry and Nutrition, 45(3): 285-291.
· Hirai, S., Kim, Y.I., Goto, T., Kang, M.S., Yoshimura, M., Obata, A., et al. (2007). Inhibitory effect of naringenin chalcone on inflammatory changes in the interaction between adipocytes and macrophages. Life Science, 81: 1272-1279.
· Jain, A., Yadav, A., Bozhkov, A.I., Padalko, V.I. and Flora, S.J. (2011). Therapeutic efficacy of silymarin and naringenin in reducing arsenic-induced hepatic damage in young rats. Ecotoxicology and Environmental Safety, 74: 607-614.
· Jong-Hwa, P., Jin-Woo, L., Hyun-Dong, P., Ssang-Goo, C., Seung-Yeol, N., Yong-Sun, P., et al. (2010). Cytotoxic Effects of 7-O-Butyl Naringenin on Human Breast Cancer MCF-7 Cells. Food Science and Biotechnology, 19: 717-724.
· Kara, S., Gencer, B., Karaca, T., Tufan, H.A., Arikan, S., Ersan, I., et al. (2014). Protective Effect of Hesperetin and Naringenin against Apoptosis in Ischemia/Reperfusion-Induced Retinal Injury in Rats. Scientific World Journal, 797824.
· Kawaii, S., Tomono, Y., Katase, E., Ogawa, E. and Yano M. (1999). Quantitation of flavonoid constituents in Citrus fruits. Journal of Agricultural and Food Chemistry, 47(9): 3565-3571.
· Kinoshita, T., Lepp, Z., Kawai, Y., Terao, J. and Chuman H. (2006). An integrated database of flavonoids. BioFactors, 26(3): 179-188.
· Koike, K., Moore, F.A., Moore, E.E., Read, R.A., Carl, V.S. and Banerjee, A. (1993). Gut ischemia mediates lung injury by a xanthine oxidasedependent neutrophil mechanism. Journal of Surgical Research, 54(5): 469-473.
· Kremer, J.M. (2004): Toward a better understanding of methotrexate. Arthritis and Rheumatology, 50:1370-1382.
· Lee, J. and Kim, G. (2010). Evaluation of antioxidant and inhibitory activities for different subclasses flavonoids on enzymes for rheumatoid arthritis. Journal of Food Science, 75(7): H212-H217.
· Lee, G. and Luna, H.T. (1988). Manual of histologic staining methods of the armed forces institute of pathology. Third Edition. The Blakiston Division Mc Graw. Hill Book Company, pp: 32-107.
· Lisa, J., Wilcox, M. and Borradaile, W. (1999). Antiatherogenic Properties of Naringenin, a Citrus Flavonoid. Cardiovascular Drug Reviews, 17:160-178.
· Mallick, J.H., Yang, W.X., Winslet, M.C. and Seifalian, A.M. (2004). Ischemia–reperfusion injury of the intestine and protective strategies against injury. Digestive Diseases and Sciences, 49: 1359-1377.
· Mallick, J.H., Yang, W.X., Winslet, M.C. and Seifalian, A.M. (2005). Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine. World Journal of Gastroenterology 11:7308-7313.
· Miller, N.J., Rice-Evans, C., Davies, M.J., Gopinathan, V. and Milner, A. (1993). A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clinical Science, 84: 407-412.
· Miyazono, Y., Gao, F. and Horie, T. (2004). Oxidative stress contributes to methotrexate-induced small intestinal toxicity in rats. Scand. Journal of Gastroenterology, 39(11): 1119-1127.
· Miyake, Y., Minato, K., Fukumoto, S., Yamamoto, K., Oya-ito, T., Kawakishi, S., et al. (2003). New potent antioxidative hydroxyflavanones produced with Aspergillus saitoi from flavanone glycoside in citrus fruit. Bioscience, Biotechnology and Biochemistry, 67(7): 1443-1450.
· Mohandas, J., Marshall, J.J., Duggin, G.G., Horvath, J.S. and Tiller, D.J. (1984). Low activities of glutathione-related enzymes as factors in the genesis of urinary bladder cancer. Cancer Research, 44(11): 5086-5091.
· Moore, E.E., Moore, F.A., Franciose, R.J., Kim, F.J., Biffl, W.L. and Banerjee, A. (1994). The postischemic gut serves as a priming bed for circulating neutrophils that provoke multiple organ failure. Journal of Trauma, 37(6): 881-887.
· Mulvihill, E.E., Allister, E.M., Sutherland, B.G., Telford, D.E., Sawyez, C.G., Edwards, J.Y., et al. (2009). Markle JM, Hegele RA, Huff MW. Naringenin prevents dyslipidemia, apolipoprotein B overproduction, and hyperinsulinemia in LDL receptor-null mice with diet-induced insulin resistance. Diabetes, 58: 2198-2210.
· Naik, S.R. and Panda, V.S. (2008). Hepatoprotective effect of Ginkgoselect phytosome® in rifampicin induced liver injury in rats: Evidence of antioxidant activity. Fitoterapia, 79(6): 439-445.
· Nalini, N., Aranganathan, S. and Kabalimurthy, J. (2012). Chemopreventive efficacy of hesperetin (citrus flavonone) against 1, 2-dimethylhydrazine-induced rat colon carcinogenesis. Toxicology Mechanisms and Methods, 22: 397-408.
· Nishikimi, M., Appaji, N. and Yagi, K. (1972). The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochemical and Biophysical Research Communications, 46(2): 849-854.
· Okudan, N., Belviranli, M., Gökbel, H., Oz M. and Kumak A. (2013). Protective effects of curcumin supplementation on intestinal ischemia reperfusion injury. Phytomedicine, 20(10): 844-848.
· Oršolić, N., Gajski, G., Garaj-Vrhovac, V., Dikić, D., Prskalo, Z.Š. and Sirovina, D. (2011). DNA-protective effects of quercetin or naringenin in alloxan-induced diabetic mice. European Journal of Pharmacology, 656: 110-118.
· Ortiz-Andrade, R.R., Sánchez-Salgado, J.C., Navarrete-Vázquez, G., Webster, S.P., Binnie, M., García-Jiménez, S., et al. (2008). Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulation. Diabetes, Obesity and Metabolism, 10: 1097-1104.
· Ozkan, O.V., Yuzbasioglu, M.F., Ciralik, H., Kurutas, E.B., Yonden Z., Aydin, M., et al. (2009). Resveratrol, a natural antioxidant, attenuates intestinal ischemia/reperfusion injury in rats. Tohoku Journal of Experimental Medicine, 218: 251-258.
· Pollard, S.E., Whiteman, M. and Spencer, J.P.E. (2006). Modulation of peroxynitrite-induced fibroblast injury by hesperetin: a role for intracellular scavenging and modulation of ERK signalling. Biochemical and Biophysical Research Communications, 347(4): 916-923.
· Rahigude, A., Bhutada, P., Kaulaskar, S., Aswar, M. and Otari, K. (2012). Participation of antioxidant and cholinergic system in protective effect of naringenin against type-2 diabetes-induced memory dysfunction in rats. Neuroscience, 226:62-72.
· Raza, S.S., Khan, M.M., Ahmad, A., Ashafaq, M., Islam, F., Wagner, A.P., et al. (2013). Neuroprotective effect of naringenin is mediated through suppression of NF-κB signaling pathway in experimental stroke. Neuroscience, 230: 157-171.
· Rotruck, J.T., Pope, A.L., Ganther, H.E., Swanson, A.B., Hafeman, D.G. and Hoekstra, W.G. (1973). Selenium: biochemical role as a component of glutathione peroxidase. Science, 179(73): 588-590.
· Sener, G., Eksioglu-Demiralp, E., Cetiner, M., Ercan, F. and Yegen, B.C. (2006). β glucan ameliorates methotrexate induced oxidative organ injury via its antioxidant and immunomodulatory effects. European Journal of Pharmacology, 542: 170-178.
· Swank, G.M. and Deitch, E.A. (1996). Role of the gut in multiple organ failure: Bacterial translocation and permeability changes. World Journal of Surgery, 20(4): 411-417.
· Teke, Z., Kabay, B., Aytekin, F.O., Yenisey, C., Demirkan, N.C., Sacar, M., et al. (2007). Pyrrolidine dithiocarbamate prevents 60 minutes of warm mesenteric ischemia/reperfusion injury in rats. American Journal of Surgical Pathology, 194: 255-262.
· Terzi, A., Coban, S., Yildiz, F., Ates, M., Bitiren, M., Taskin, A., et al. (2010). Protective effects of Nigella sativa on intestinal ischemia-reperfusion injury in rats. Journal of Investigative Surgery, 23(1): 21-27.
· Testai, L., Martelli, A., Cristofaro, M., Breschi, M.C. and Calderone V. (2013). Cardioprotective effects of different flavonoids against myocardial ischaemia/reperfusion injury in Langendorff-perfused rat hearts. Journal of Pharmacology and Pharmacotherapeutics, 65: 750-756.
· Ustundag, B., Kazez, A., Demirbag, M., Canatan, H., Halifeoglu, I. and Ozercan, I.H. (2000). Protective effect of melatonin on antioxidative system in experimental ischemia–reperfusion of rat intestine. Cellular Physiology and Biochemistry, 10: 229-236.
· Viswa, K.K., Premila, A. and Bina, I. (2007). Alteration in antioxidant defense mechanisms in the small intestines of methotrexate treated rat may contribute to its gastrointestinal toxicity. Cancer Therapy, 5: 501-510.
· Yamamoto, S., Tanabe, M., Wakabayashi, G., Shimazu, M., Matsumoto, K. and Kitajima, M. (2001). The role of tumor necrosis factor-alpha and interleukin-1 beta in ischemia–reperfusion injury of the rat small intestine. Journal of Surgical Research, 99: 134-141.
· Yildiz, Y., Kose, H., Cecen, S., Ergin, K., Demir, E.M. and Serter, M. (2010). Protective effect of leflunomide on intestinal ischemia–reperfusion injury: leflunomide against intestinal ischemia–reperfusion. Digestive Diseases and Sciences, 55: 245-252.
· Yildiz, Y., Serter, M., Ek, R.O., Ergin, K., Cecen, S., Demir, E.M. and Yenisey, C. (2009). Protective effect of caffeic acid phenethyl ester on intestinal ischemia–reperfusion injury. Digestive Diseases and Sciences, 54: 738-744.
· Zbarsky, V., Datla K.P., Parkar, S., Rai, D.K., Aruoma, O.I. and Dexter, D.T. (2005). Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and fisetin in a 6-OHDA model of Parkinson’s disease. Free Radical Research, 39: 1119-1125.
