مطالعه اثر عصاره هیدروالکلی ریشه گیاه شلغم بر مسمومیت کبدی ناشی از متوترکسات در موش صحرایی
محورهای موضوعی :
آسیب شناسی درمانگاهی دامپزشکی
سعید خداداد
1
(دانش آموخته دکترای حرفه ای دامپزشکی، دانشکده دامپزشکی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز، ایران.)
داریوش مهاجری
2
(استاد، گروه پاتوبیولوژی، دانشگاه آزاد اسلامی واحد تبریز، تبریز، ایران)
رامین کفاشی الهی
3
(گروه علوم درمانگاهی، دانشکده دامپزشکی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز، ایران.)
تاریخ دریافت : 1396/08/08
تاریخ پذیرش : 1397/03/23
تاریخ انتشار : 1397/06/01
کلید واژه:
موش صحرایی,
مسمومیت کبدی,
متوترکسات,
ریشه گیاه شلغم,
چکیده مقاله :
متوترکسات به عنوان یک داروی ضدسرطان، در دوزهای بالا برای کبد سمّی است. معلوم گردیده است که استرس اکسیداتیو در سمّیت متوترکسات دخیل است. با توجه به خواص آنتی اکسیدانی ریشه گیاه شلغم، این مطالعه، برای ارزیابی اثرات محافظتی عصاره هیدروالکلی ریشه شلغم در برابر سمیّت کبدی ناشی از متوترکسات در موش صحرایی انجام شد. بدین منظور 40 سر موش صحرایی نر ویستار به طور تصادفی در چهار گروه مساوی تقسیم گردیدند. گروه 1 به عنوان شاهد انتخاب شد. به گروه های 2 و 4، ریشه گیاه شلغم (mg/kg 200) به مدت 15 روز متمادی گاواژ گردید. گروه های 3 و 4 تک دوز متوترکسات (mg/kg 20)را در دهمین روز آزمایش به طور داخل صفاقی دریافت کردند. در پایان، سطوح سرمی آنزیم‌های آسپارتات آمینوترانسفراز، آلانین آمینوترانسفراز و آلکالین فسفاتاز و بیلی روبین تام، آلبومین و پروتئین تام گروه ها اندازه گیری شد. میزان مالون دی آلدئید و فعالیت آنزیم های سوپراکسید دیسموتاز، کاتالاز، گلوتاتیون پراکسیداز و گلوتاتیون ردوکتاز نیز در هموژنات بافت کبد اندازه گیری شد. از بافت کبد موش ها مقاطع بافتی تهیه و در نهایت، یافته های بیوشیمیایی با نتایج هیستوپاتولوژی تطبیق داده شد. در گروه 4، عصاره ریشه شلغم به طور معنی داری (05/0p<) میزان افزایش یافته آنزیم‌های شاخص آسیب کبد و بیلی روبین تام را کاهش و سطوح کاهش یافته آلبومین و پروتئین تام سرم را به طور معنی داری (05/0p<) افزایش داد. در این گروه، عصاره ریشه شلغمبه طور معنی داری (05/0p<) میزان پراکسیداسیون لیپیدی را کاهش و سطوح آنتی اکسیدان های کبد را افزایش داد. از لحاظ هیستوپاتولوژی نیز تغییرات بافتی شامل آماس، تغییرات دژنراتیو و نکروز، همراستا با یافته های بیوشیمیایی بودند. نتایج نشان داد عصاره ریشه شلغمبا خواص آنتی‌اکسیدانی خود، کبد موش‌های صحرایی را در برابر سمّیت ناشی از متوترکسات محافظت می کند.
چکیده انگلیسی:
Methotrexate as an anticancer drug is hepatotoxic at high doses. It has been proven that oxidative stress is involved in methotrexate induced toxicity. Because of antioxidant potential of Brassica rapa. L root, this study was undertaken to examine the protective effect of hydroalcoholic extract of Brasscia rapa L. (BR) root on methotrexate induced hepatotoxicity in the rat. For this purpose, forty male Wistar rats were randomly divided into four equal groups. Group 1 was used as control; groups 2 and 4 were orally treated with BR root extract (200 mg/kg) for 15 consecutive days. Groups 3 and 4 received a single intraperitoneal dose of methotrexate (20 mg/kg) on the 10th day of the experiment. At the end of the experiment, serumic levels of AST and ALT, ALP and total bilirubin, albumin and total proteins were assessed. Malondialdehyde and activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase were assayed in liver homogenates. Tissue sections were prepared from the liver and finally, the biochemical findings were compared with histopathological results. In group 4, BR root extract significantly (p<0.05) decreased the levels of serum biomarkers of hepatic injury and total bilirubin, and significantly increased the levels of serum albumin and total proteins (p<0.05). Also BR root extract significantly (p<0.05) decreased the lipid peroxidation and elevated the decreased values of hepatic antioxidants in this group. Histopathologic changes including degeneration, inflammation and necrosis were in agreement with biochemical findings. The results indicated that BR root extract, because of its antioxidant potential, exerts a protective effect against methotrexate induced hepatotoxicity in rats.
منابع و مأخذ:
Choi, H.J., Han, M.J., Baek, N.I., Kim, D.H., Jung, H.G. and Kim, N.J. (2006). Hepatoprotective effects of Brassica rapa (Turnip) on d-Galactosamine induced liver injured rats. Korean Journal of Pharmacognosy, 37(4): 258-265.
Claiborne, A. (1985). Catalase activity. In: CRC Handbook of Methods for Oxygen Radical Research. Boca Raton, F.L. editor. Florida: CRC Press, Boca Raton, pp: 283-284.
Fernandes, F., Valentão, P., Sousa, C., Pereira, J.A., Seabra, R.M. and Andrade, P.B. (2007). Chemical and antioxidative assessment of dietaryturnip (Brassica rapa var. rapa L.). Food Chemistry, 105(3): 1003-1010.
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.
Franciscoa, M., Morenob, D.A., Carteaa, M.E., Ferreresb, F., Viguerab, C.G. and Velascoa, P. (2009). Simultaneous identification of glucosinolates and phenolic compounds in a representative collection of vegetable Brassica rapa. Journal of Chromatography A, 1216(38): 6611-6619.
Frei, A., Zimmermann, A. and Weigand, K. (1984). The N-terminal propeptide of collagen type III in serum reflects activity and degree of fibrosis in patients with chronic liver disease. Hepatology, 4(5): 830-834.
Ghaffari, A.R., Noshad, H., Ostadi, A., Ghojazadeh, M. and Asadi, P. (2011). The effects of milk thistle on hepatic fibrosis due to methotrexate in rat. Hepatitis Monthly, 11(6): 464-468.
Hemeida, R.A.M. and Mohafez, O.M. (2008). Curcumin attenuates methotraxate-induced hepatic oxidative damage in rats. Journal of the Egyptian National Cancer Institute, 20(2): 141-148.
Jouyban, A., Shaghaghi, M., Manzoori, J., Soleymani, J. and Jalilvaez-Gharamaleki, J. (2011). Determination of methotrexate in biological fluids and a parenteral injection using terbium-sensitized method. Iranian Journal of Pharmaceutical Research, 10(4): 695-704.
Jung, U.J., Baek, N.I., Chung, H.G., Bang, M.H., Jeong, T.S., Lee, K.T., et al. (2008). Effects of the ethanol extract of the roots of Brassica rapa on glucose and lipid metabolism in C57BL/KsJ-db/db mice. Clinical Nutrition, 27(1): 158-167.
Kim, Y.H., Kim, Y.W., Oh, Y.J., Back, N.I., Chung, S.A., Chung, H.G., et al. (2006). Protective effect of the ethanol extract of the roots of Brassica rapa on cisplatin-induced nephrotoxicity in LLC-PK1 cells and rats. Biological and Pharmaceutical Bulletin, 29(12): 2436-2441.
Kind, P.R. and King, E.J. (1954). Estimation of plasma phosphates by determination of hydrolyzed phenol with antipyrin. Journal of Clinical Pathology, 7(4): 322-326.
Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951). Protein measurement with the folin phenol reagent. Journal of Biological Chemistry, 193: 265-275.
Malloy, H.T. and Evelyn, K.A. (1937). The determination of bilirubin level with the photoelectric colorimeter. Journal of Biological Chemistry, 119: 481-484.
Mithen, R., Faulkner, K., Magrath, R., Rose, P., Williamson, G. and Marquez, J. (2003). Development of isothiocyanate-enriched broccoli, and its enhanced ability to induce phase 2 detoxification enzymes in mammalian cells. Theoretical and Applied Genetics, 106(4): 727-734.
Mohandas, J., Marshal, J.J., Duggin, G.G., Horvath, J.S. and Tiller, D.G. (1984). Low activities of glutathione-related enzymes as factors in the genesis of urinary bladder cancer. Cancer Research, 44(11): 5086-5091.
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.
Rafatullah, S., Al-Yahya, M., Mossa, J., Galal, A. and El-Tahir, K. (2006). Preliminary phytochemical and hepatoprotective studies on turnip Brassica rapa L. International Journal of Pharmacology, 2(6): 670-673.
Reitman, S. and Frankel, S. (1957). A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminase. American Journal of Clinical Pathology, 28: 56-63.
Rezaei Moghadam, A., Mohajeri, D., Namvaran-Abbas-Abad, A., Manafi, H. and Mazani, M. (2013). Protective effect of turmeric extract on methotrexate-induced intestinal damage and oxidative stress. Chinese Journal of Natural Medicines, 11(5): 477-483.
Rezaei Moghadam, A., Tutunchi, S., Namvaran-Abbas-Abad, A., Yazdi, M., Bonyadi, F., Mohajeri, D., et al. (2015). Pre-administration of turmeric prevents methotrexate-induced liver toxicity and oxidative stress. BMC Complementary and Alternative Medicine, 15(246): 1-13.
Rotruck, I.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: 588-590.
Russo, V.M. (2008). Vegetable Brassicas and Related Crucifers. Crop production science in horticulture 14. International Journal of Vegetable Science, 14(1): 93.
Shukia, R., Sharma, S.B., Puri, D., Prabhu, K.M. and Murthy, P.S. (2000). Medicinal plants for treatment of diabetes mellitus. Indian Journal of Clinical Biochemistry, 15(Suppl 1): 169-177.
Thabrew, M.I., Joice, P.D. and Rajatissa, W. (1987). A comparative study of the efficacy of Pavetta indica and Osbeckia octanda in the treatment of liver dysfunction. Planta Medica, 53(3): 239-241.
Traka, M. and Mithen, R. (2008). Glucosinolates, isothiocyanates and human health. Phytochemistry Reviews, 8(1): 269-282.
Venkatesan, N., Punithavathi, D. and Arumugam, V. (2000). Curcumin prevents adriamycin nephrotoxicity in rats. British Journal of Pharmacology, 129(2): 231-234.
Yüncü, M., Eralp, A. and Celõk, A. (2006). Effect of aged garlic extract against methotrexate induced damage to the small intestine in rats. Phytotherapy Research, 20(6): 504-510.
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Choi, H.J., Han, M.J., Baek, N.I., Kim, D.H., Jung, H.G. and Kim, N.J. (2006). Hepatoprotective effects of Brassica rapa (Turnip) on d-Galactosamine induced liver injured rats. Korean Journal of Pharmacognosy, 37(4): 258-265.
Claiborne, A. (1985). Catalase activity. In: CRC Handbook of Methods for Oxygen Radical Research. Boca Raton, F.L. editor. Florida: CRC Press, Boca Raton, pp: 283-284.
Fernandes, F., Valentão, P., Sousa, C., Pereira, J.A., Seabra, R.M. and Andrade, P.B. (2007). Chemical and antioxidative assessment of dietaryturnip (Brassica rapa var. rapa L.). Food Chemistry, 105(3): 1003-1010.
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.
Franciscoa, M., Morenob, D.A., Carteaa, M.E., Ferreresb, F., Viguerab, C.G. and Velascoa, P. (2009). Simultaneous identification of glucosinolates and phenolic compounds in a representative collection of vegetable Brassica rapa. Journal of Chromatography A, 1216(38): 6611-6619.
Frei, A., Zimmermann, A. and Weigand, K. (1984). The N-terminal propeptide of collagen type III in serum reflects activity and degree of fibrosis in patients with chronic liver disease. Hepatology, 4(5): 830-834.
Ghaffari, A.R., Noshad, H., Ostadi, A., Ghojazadeh, M. and Asadi, P. (2011). The effects of milk thistle on hepatic fibrosis due to methotrexate in rat. Hepatitis Monthly, 11(6): 464-468.
Hemeida, R.A.M. and Mohafez, O.M. (2008). Curcumin attenuates methotraxate-induced hepatic oxidative damage in rats. Journal of the Egyptian National Cancer Institute, 20(2): 141-148.
Jouyban, A., Shaghaghi, M., Manzoori, J., Soleymani, J. and Jalilvaez-Gharamaleki, J. (2011). Determination of methotrexate in biological fluids and a parenteral injection using terbium-sensitized method. Iranian Journal of Pharmaceutical Research, 10(4): 695-704.
Jung, U.J., Baek, N.I., Chung, H.G., Bang, M.H., Jeong, T.S., Lee, K.T., et al. (2008). Effects of the ethanol extract of the roots of Brassica rapa on glucose and lipid metabolism in C57BL/KsJ-db/db mice. Clinical Nutrition, 27(1): 158-167.
Kim, Y.H., Kim, Y.W., Oh, Y.J., Back, N.I., Chung, S.A., Chung, H.G., et al. (2006). Protective effect of the ethanol extract of the roots of Brassica rapa on cisplatin-induced nephrotoxicity in LLC-PK1 cells and rats. Biological and Pharmaceutical Bulletin, 29(12): 2436-2441.
Kind, P.R. and King, E.J. (1954). Estimation of plasma phosphates by determination of hydrolyzed phenol with antipyrin. Journal of Clinical Pathology, 7(4): 322-326.
Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951). Protein measurement with the folin phenol reagent. Journal of Biological Chemistry, 193: 265-275.
Malloy, H.T. and Evelyn, K.A. (1937). The determination of bilirubin level with the photoelectric colorimeter. Journal of Biological Chemistry, 119: 481-484.
Mithen, R., Faulkner, K., Magrath, R., Rose, P., Williamson, G. and Marquez, J. (2003). Development of isothiocyanate-enriched broccoli, and its enhanced ability to induce phase 2 detoxification enzymes in mammalian cells. Theoretical and Applied Genetics, 106(4): 727-734.
Mohandas, J., Marshal, J.J., Duggin, G.G., Horvath, J.S. and Tiller, D.G. (1984). Low activities of glutathione-related enzymes as factors in the genesis of urinary bladder cancer. Cancer Research, 44(11): 5086-5091.
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.
Rafatullah, S., Al-Yahya, M., Mossa, J., Galal, A. and El-Tahir, K. (2006). Preliminary phytochemical and hepatoprotective studies on turnip Brassica rapa L. International Journal of Pharmacology, 2(6): 670-673.
Reitman, S. and Frankel, S. (1957). A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminase. American Journal of Clinical Pathology, 28: 56-63.
Rezaei Moghadam, A., Mohajeri, D., Namvaran-Abbas-Abad, A., Manafi, H. and Mazani, M. (2013). Protective effect of turmeric extract on methotrexate-induced intestinal damage and oxidative stress. Chinese Journal of Natural Medicines, 11(5): 477-483.
Rezaei Moghadam, A., Tutunchi, S., Namvaran-Abbas-Abad, A., Yazdi, M., Bonyadi, F., Mohajeri, D., et al. (2015). Pre-administration of turmeric prevents methotrexate-induced liver toxicity and oxidative stress. BMC Complementary and Alternative Medicine, 15(246): 1-13.
Rotruck, I.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: 588-590.
Russo, V.M. (2008). Vegetable Brassicas and Related Crucifers. Crop production science in horticulture 14. International Journal of Vegetable Science, 14(1): 93.
Shukia, R., Sharma, S.B., Puri, D., Prabhu, K.M. and Murthy, P.S. (2000). Medicinal plants for treatment of diabetes mellitus. Indian Journal of Clinical Biochemistry, 15(Suppl 1): 169-177.
Thabrew, M.I., Joice, P.D. and Rajatissa, W. (1987). A comparative study of the efficacy of Pavetta indica and Osbeckia octanda in the treatment of liver dysfunction. Planta Medica, 53(3): 239-241.
Traka, M. and Mithen, R. (2008). Glucosinolates, isothiocyanates and human health. Phytochemistry Reviews, 8(1): 269-282.
Venkatesan, N., Punithavathi, D. and Arumugam, V. (2000). Curcumin prevents adriamycin nephrotoxicity in rats. British Journal of Pharmacology, 129(2): 231-234.
Yüncü, M., Eralp, A. and Celõk, A. (2006). Effect of aged garlic extract against methotrexate induced damage to the small intestine in rats. Phytotherapy Research, 20(6): 504-510.
