نقش ویتامینA در پیشگیری از صدمات جنینی ناشی از تزریق لیپوپلی‌ساکارید باکتری اشریشیا کولای در موش صحرایی
الموضوعات :عارف دلخوش 1 , مسعود دل آشوب 2 , منصور خاکپور 3
1 - دانش‌آموخته دکترای حرفه‌ای دامپزشکی، دانشکده دامپزشکی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز، ایران.
2 - استادیار گروه علوم پایه، دانشکده دامپزشکی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز، ایران.
3 - استادیار گروه پاتوبیولوژی، دانشکده دامپزشکی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز، ایران.
الکلمات المفتاحية: آنتی‌اکسیدان, لیپوپلی‌ساکارید, ویتامین A, اشریشیاکولای, آسیب جنینی,
ملخص المقالة :
لیپوپلی‌ساکارید ها از عوامل آسیب‌‌رسان به جنین در طی مراحل رشد می‌باشند. تاخیر در رشد جنین ، مرگ داخل رحمی جنین، جذب جنینی و زایمان زودرس، با استرس اکسیداتیو ناشی از لیپوپلی‌ساکارید ها مرتبط می باشد. در تحقیق حاضر اثر محافظتی ویتامین Aدر برابر صدمات جنینی ناشی از لیپوپلی‌ساکاریدها در موش صحرایی بررسی شد. در این مطالعه تجربی تعداد 48 سر موش صحرایی آبستن به 4 گروه تقسیم و در روزهای 15 تا 17 آبستنی، به موش های گروه های اول و دوم، مقدار 75 میکروگرم به ازای هر کیلوگرم وزن بدن از لیپوپلی ساکارید باکتری اشریشیاکولای به صورت داخل صفاقی تزریق شد. همچنین موش های گروه های دوم و سوم یک هفته قبل از تزریق لیپوپلی ساکارید، روزانه مقدار 100 میلی گرم بر کیلوگرم وزن بدن، ویتامین A به صورت داخل عضلانی دریافت کردند. به موش هایگروه چهارم به عنوان شاهد ، برای مشابه‌سازی استرس تزریق، دارونما تزریق شد. در روز 18 تمامی موش ها آسان کشی شدند. تعداد جنین‌های زنده و مرده شمارش شده، سپس جنین های زنده وزن گردیده و طول تاج -کفل، متا کارپ، متاتارس، بندهای انگشتان دست و پا و جناغ اندازه گیری شد. همچنین در کبد مادر،کبد جنین و جفت، میزان مالونیل دی آلدئید و گلوتاتیون اندازه گیری شد. تجویز لیپوپلی‌ساکارید به طور معنی‌داری موجب افزایش تلفات جنینی، کاهش وزن جنین و طول تاج -کفل در جنین‌های زنده و کاهش استخوانی شدن اسکلت در متا کارپ، متاتارس، بندهای انگشتان دست و پا و جناغ شد (05/0p <). تجویز همزمان ویتامین A و لیپوپلی‌ساکارید موجب کاهش آسیب‌های ناشی از لیپوپلی‌ساکارید و بهبود صدمات مربوطه شد که نشان دهنده قدرت حفاظتی ویتامین Aدر برابر عوارض ناشی از لیپوپلی ساکارید ها در جنین می باشد.
المصادر:
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Altavilla, D., Squadrito, G., Minutoli, L., Deodato, B., Bova, A., Sardella, A., et al. (2002). Inhibition of nuclear factor-κb Activation by Irfi 042, protects against endotoxin-induced shock. Cardiovascular Research, 54(3): 684-693.
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Cadenas, E. and Packer, L. (1996): Handbook of Antioxidants. Marcel Dekker Inc, 3(6): 205-284.
Carey, L.C., Berbée, P.L., Coyle, P., Philcox, J.C. and Rofe, A.M. (2003). Zinc treatment prevents lipopolysaccharide-induced teratogenicity in mice. Birth Defects Research Part A: Clinical and Molecular Teratology, 67(4): 240-245.
Chaouat, G., Menu, E., Clark, D., Dy, M., Minkowski, M. and Wegmann, T. (1990). Control of fetal survival in Cba× Dba/2 mice by lymphokine therapy. Journal of Reproduction and Fertility, 89(2): 447-458.
Chen, Y.H., Wang, J.P., Wang, H., Sun, M.F., Wei, L.Z., Wei, W., et al. (2005). Lipopolysaccharide treatment downregulates the expression of the pregnane X receptor, Cyp3a11 and Mdr1a genes in mouse placenta. Toxicology, 211(3): 242-252.
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Fukui, H., Brauner, B., Bode, J.C. and Bode, C. (1991). Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay. Journal of Hepatology, 12(2): 162-169.
Gendron, R., Nestel, F., Lapp, W. and Baines, M. (1990). Lipopolysaccharide-Induced fetal resorption in mice is associated with the intrauterine production of tumour necrosis factor-alpha. Journal of Reproduction and Fertility, 90(2): 395-402.
Gibbs, R.S. and Duff, P. (1991). Progress in Pathogenesis and management of clinical intraamniotic infection. American Journal of Obstetrics and Gynecology, 164(5): 1317-1326.
Gonzalez-Reyes, S., Martinez, L., Martinez-Calonge, W., Fernandez-Dumont, V. and Tovar, J.A. (2006). Effects of antioxidant vitamins on molecular regulators involved in lung hypoplasia induced by nitrofen. Journal of Pediatric Surgery, 41(8): 1446-1452.
Griffith, O.W. (1980). Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Analytical Biochemistry, 106(1): 207-212.
Haddad, E., Duclos, A. and Baines, M. (1995). Early embryo loss is associated with local production of nitric oxide by decidual mononuclear cells. The Journal of experimental Medicine, 182(4): 1143-1151.
Hillier, S., Martius, J., Krohn, M., Kiviat, N., Holmes, K. and Eschenbach, D. (1989). A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity. International Journal of Gynecology and Obstetrics, 29(1): 96-97.
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Lanning, J., Hilbelink, D. and Chen, L. (1983). Teratogeneic effects of endotoxin on the golden hamster. Teratogenesis, Carcinogenesis and Mutagenesis, 3(2): 145-149.
Li, X.J., Zhang, G.X., Sun, N., Sun, Y., Yang, L.Z. and Du, Y.J. (2013). Protective effects of erythropoietin on endotoxin-related organ injury in rats. Journal of Huazhong University of Science and Technology, 33(5): 680-686.
Nordberg, J. and Arner, E.S. (2001). Reactive oxygen species, ntioxidants and the mammalian thioredoxin system. Free Radical Biology and Medicine, 31(11): 1287-1312.
Ogando, D.G., Paz, M. and Franchi, A.M. (2003). The functional role of increased production of nitric oxide in lipopolysaccharide induced embryonic resorption in mice. Reproduction, 125(1): 95-110.
O'sullivan, A., Dore, C., Boyle, S., Coid, C. and Johnson, A. (1988). The effect of campylobacter lipopolysaccharide on fetal development in the mouse. Journal of Medical Microbiology, 26(2): 101-105.
Parra, T., de Arriba, G., Conejo, J.R., Cantero, M., Arribas, I., Rodríguez-Puyol, D., et al. (1998). Effect of vitamin E on cyclosporine nephrotoxicity. Transplantation, 66(10): 1325-1329.
Parant, M. and Chedid, L. (1964). Protective Effect of Chlorpromazine against endotoxin-induced abortion. Experimental Biology and Medicine, 116(4): 906-909.
Raetz, C.R., Ulevitch, R.J., Wright, S., Sibley, C., Ding, A. and Nathan, C. (1991). Gram-negative endotoxin: An extraordinary lipid with profound effects on eukaryotic signal transduction. The FASEB Journal, 5(12): 2652-2660.
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Aliverti, V., Bonanomi, L., Giavini, E., Leone, V. and Mariani, L. (1979). The extent of fetal ossification as an index of delayed development in teratogenic studies on the rat. Teratology, 20(2): 237-242.
Altavilla, D., Squadrito, G., Minutoli, L., Deodato, B., Bova, A., Sardella, A., et al. (2002). Inhibition of nuclear factor-κb Activation by Irfi 042, protects against endotoxin-induced shock. Cardiovascular Research, 54(3): 684-693.
Barker, D.J., Godfrey, K.M., Gluckman, P.D., Harding, J.E., Owens, J.A. and Robinson, J.S. (1993). Fetal nutrition and cardiovascular disease in adult life. The Lancet, 341(8850): 938-941.
Bautista, A.P., Meszaros, K., Bojta, J. and Spitzer, J.J. (1990). Superoxide anion generation in the liver during the early stage of endotoxemia in rats. Journal of Leukocyte Biology, 48(2): 123-128.
Ben-Shaul, V., Lomnitski, L., Nyska, A., Zurovsky, Y., Bergman, M. and Grossman, S. (2001). The effect of natural antioxidants, nao and apocynin, on oxidative stress in the rat heart following LPS challenge. Toxicology Letters, 123(1): 1-10.
Biswas, S.K. and Lopez-Collazo, E. (2009). Endotoxin tolerance: New mechanisms, molecules and clinical Significance. Trends in Immunology, 30(10): 475-487.
Block, G., Jensen, C.D., Morrow, J.D., Holland, N., Norkus, E.P., Milne, G.L., et al. (2008). The effect of vitamins C and E on biomarkers of oxidative stress depends on baseline level. Free Radical Biology and Medicine, 45(4): 377-384.
Buhimschi, I.A., Buhimschi, C.S. and Weiner, C.P. (2003). Protective effect of N-acetylcysteine against fetal death and preterm labor induced by maternal inflammation. American Journal of Obstetrics And Gynecology, 188(1): 203-208.
Cadenas, E. and Packer, L. (1996): Handbook of Antioxidants. Marcel Dekker Inc, 3(6): 205-284.
Carey, L.C., Berbée, P.L., Coyle, P., Philcox, J.C. and Rofe, A.M. (2003). Zinc treatment prevents lipopolysaccharide-induced teratogenicity in mice. Birth Defects Research Part A: Clinical and Molecular Teratology, 67(4): 240-245.
Chaouat, G., Menu, E., Clark, D., Dy, M., Minkowski, M. and Wegmann, T. (1990). Control of fetal survival in Cba× Dba/2 mice by lymphokine therapy. Journal of Reproduction and Fertility, 89(2): 447-458.
Chen, Y.H., Wang, J.P., Wang, H., Sun, M.F., Wei, L.Z., Wei, W., et al. (2005). Lipopolysaccharide treatment downregulates the expression of the pregnane X receptor, Cyp3a11 and Mdr1a genes in mouse placenta. Toxicology, 211(3): 242-252.
Coe, C.L., Kramer, M., Kirschbaum, C., Netter, P. and Fuchs, E. (2002). Prenatal stress diminishes the cytokine response of leukocytes to endotoxin stimulation in juvenile rhesus monkeys. The Journal of Clinical Endocrinology and Metabolism, 87(2): 675-681.
Coid, C. (1976). Bacterial endotoxin and impaired fetal development. Experientia, 32(6): 735-736.
Collins, J., Smith, M., Arnold, R.R. and Offenbacher, S. (1994). Effects of Escherichia coli and Porphyromonas gingivalis lipopolysaccharide on pregnancy outcome in the golden hamster. Infection and Immunity, 62(10): 4652-4655.
Cottrell, E.C. and Seckl, J. (2009). Prenatal Stress, glucocorticoids and the programming of adult disease. Frontiers in Behavioral Neuroscience, 3: 19.
Coyle, P., Tran, N., Fung, J.N., Summers, B.L. and Rofe, A.M. (2009). Maternal dietary zinc supplementation prevents aberrant behaviour in an object recognition task in mice offspring exposed to LPS in early pregnancy. Behavioural brain research, 197(1): 210-218.
Delashoub, M. and Khojasteh, S.M.B. (2012). An Investigation on protective effects of vitamin E against Lipopolysaccharide-induced fetal injuries in rat. Advances in Environmental Biology, 6(8): 2274-2279.
Fukui, H., Brauner, B., Bode, J.C. and Bode, C. (1991). Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay. Journal of Hepatology, 12(2): 162-169.
Gendron, R., Nestel, F., Lapp, W. and Baines, M. (1990). Lipopolysaccharide-Induced fetal resorption in mice is associated with the intrauterine production of tumour necrosis factor-alpha. Journal of Reproduction and Fertility, 90(2): 395-402.
Gibbs, R.S. and Duff, P. (1991). Progress in Pathogenesis and management of clinical intraamniotic infection. American Journal of Obstetrics and Gynecology, 164(5): 1317-1326.
Gonzalez-Reyes, S., Martinez, L., Martinez-Calonge, W., Fernandez-Dumont, V. and Tovar, J.A. (2006). Effects of antioxidant vitamins on molecular regulators involved in lung hypoplasia induced by nitrofen. Journal of Pediatric Surgery, 41(8): 1446-1452.
Griffith, O.W. (1980). Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Analytical Biochemistry, 106(1): 207-212.
Haddad, E., Duclos, A. and Baines, M. (1995). Early embryo loss is associated with local production of nitric oxide by decidual mononuclear cells. The Journal of experimental Medicine, 182(4): 1143-1151.
Hillier, S., Martius, J., Krohn, M., Kiviat, N., Holmes, K. and Eschenbach, D. (1989). A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity. International Journal of Gynecology and Obstetrics, 29(1): 96-97.
Jacob, A.L., Goldberg, P.K., Bloom, N., Degenshein, G.A. and Kozinn, P.J. (1997). Endotoxin and bacteria in portal blood. Gastroenterology, 42(2): 359-365.
Kaya, H., Sezik, M., Ozkaya, O., Dittrich, R., Siebzehnrubl, E. and Wildt, L. (2004). Lipid peroxidation at various estradiol concentrations in human circulation during ovarian stimulation with exogenous gonadotropins. Hormone and Metabolic Research, 36(10): 693-695.
Lanning, J., Hilbelink, D. and Chen, L. (1983). Teratogeneic effects of endotoxin on the golden hamster. Teratogenesis, Carcinogenesis and Mutagenesis, 3(2): 145-149.
Li, X.J., Zhang, G.X., Sun, N., Sun, Y., Yang, L.Z. and Du, Y.J. (2013). Protective effects of erythropoietin on endotoxin-related organ injury in rats. Journal of Huazhong University of Science and Technology, 33(5): 680-686.
Nordberg, J. and Arner, E.S. (2001). Reactive oxygen species, ntioxidants and the mammalian thioredoxin system. Free Radical Biology and Medicine, 31(11): 1287-1312.
Ogando, D.G., Paz, M. and Franchi, A.M. (2003). The functional role of increased production of nitric oxide in lipopolysaccharide induced embryonic resorption in mice. Reproduction, 125(1): 95-110.
O'sullivan, A., Dore, C., Boyle, S., Coid, C. and Johnson, A. (1988). The effect of campylobacter lipopolysaccharide on fetal development in the mouse. Journal of Medical Microbiology, 26(2): 101-105.
Parra, T., de Arriba, G., Conejo, J.R., Cantero, M., Arribas, I., Rodríguez-Puyol, D., et al. (1998). Effect of vitamin E on cyclosporine nephrotoxicity. Transplantation, 66(10): 1325-1329.
Parant, M. and Chedid, L. (1964). Protective Effect of Chlorpromazine against endotoxin-induced abortion. Experimental Biology and Medicine, 116(4): 906-909.
Raetz, C.R., Ulevitch, R.J., Wright, S., Sibley, C., Ding, A. and Nathan, C. (1991). Gram-negative endotoxin: An extraordinary lipid with profound effects on eukaryotic signal transduction. The FASEB Journal, 5(12): 2652-2660.
Rauscher, F.M., Sanders, R.A. and Watkins, J.B. (2001). Effects of coenzyme Q10 treatment on antioxidant pathways in normal and streptozotocin-induced diabetic rats. Journal of Biochemical and Molecular Toxicology, 15(1): 41-46.
Rietschel, E.T., Kirikae, T., Schade, F.U., Mamat, U., Schmidt, G., Loppnow, H., et al. (1994). Bacterial endotoxin: Molecular relationships of structure to activity and function. The FASEB Journal, 8(2): 217-225.
Rivera, D., Olister, S., Liu, X., Thompson, J., Zhang, X., Pennline, K., et al. (1998). Interleukin-10 attenuates experimental fetal growth restriction and demise. The FASEB Journal, 12(2): 189-197.
Rizzardini, M., Carelli, M., Porras, M.C. and Cantoni, L. (1994). Mechanisms of endotoxin-induced haem oxygenase M-RNA accumulation in mouse liver: Synergism by glutathione depletion and protection by N-acetylcysteine. Biochemical Journal, 304(2): 477-483.
Rizzardini, M., Zappone, M., Villa, P., Gnocchi, P., Sironi, M., Diomede, L., et al. (1998). Kupffer cell depletion partially prevents hepatic heme oxygenase 1 messenger RNA accumulation in systemic inflammation in mice: Role of interleukin 1β. Hepatology, 27(3): 703-710.
Romero, R., Roslansky, P., Oyarzun, E., Wan, M., Emamian, M., Novitsky, T.J., et al. (1988). Labor and infection. II. Bacterial endotoxin in amniotic fluid and its relationship to the onset of preterm labor. Labor and Infection, 158(5): 1044-1049.
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