نقش ویتامین‌A در پیشگیری از صدمات جنینی ناشی از تزریق لیپوپلی‌ساکارید باکتری اشریشیا کولای در موش صحرایی

آسیب‌شناسی درمانگاهی دامپزشکی

مقاله 7، دوره 13، 1 (49) بهار، اردیبهشت 1398، صفحه 77-90   

نوع مقاله: مقاله علمی پژوهشی

شناسه دیجیتال (DOI): 10.30495/jvcp.2019.664904

نویسندگان

عارف دلخوش¹؛ مسعود دل آشوب^{* 2}؛ منصور خاکپور³

¹دانش‌آموخته دکترای حرفه‌ای دامپزشکی، دانشکده دامپزشکی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز، ایران.

²استادیار گروه علوم پایه، دانشکده دامپزشکی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز، ایران.

³استادیار گروه پاتوبیولوژی، دانشکده دامپزشکی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز، ایران.

چکیده

لیپوپلی‌ساکارید­ها 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  لیپوپلی‌ساکارید­ها مرتبط می­باشد. 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 موش­های گروه­های اول و دوم، مقدار 75 میکروگرم به ازای هر ­کیلوگرم وزن بدن از لیپوپلی­ساکارید باکتری اشریشیاکولای به صورت داخل صفاقی تزریق شد. همچنین موش­های­ گروه­های دوم و سوم یک هفته قبل از تزریق لیپوپلی­ساکارید، روزانه مقدار 100 میلی­گرم بر کیلوگرم وزن بدن، ویتامین ­A به صورت داخل عضلانی دریافت کردند. به موش­هایگروه چهارم به عنوان شاهد­، برای مشابه‌سازی استرس تزریق، دارونما تزریق شد. در روز 18 تمامی موش­ها آسان­کشی شدند. تعداد جنین‌های زنده و مرده شمارش شده، سپس جنین­های زنده وزن گردیده و طول تاج­-کفل، متا­کارپ، متاتارس، بندهای انگشتان دست و پا و جناغ اندازه­گیری شد. همچنین در کبد­­ مادر،کبد جنین و جفت، میزان مالونیل­دی­آلدئید و گلوتاتیون اندازه­گیری شد. تجویز لیپوپلی‌ساکارید به­طور معنی‌داری موجب افزایش تلفات جنینی، کاهش وزن جنین و طول تاج­-کفل در جنین‌های زنده و کاهش استخوانی شدن اسکلت در متا­کارپ، 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 نشان­دهنده قدرت حفاظتی ویتامین ­Aدر برابر عوارض ناشی از لیپوپلی­ساکارید­ها در جنین می­باشد.

کلیدواژه‌ها

ویتامین ‌A؛ لیپوپلی‌ساکارید؛ اشریشیا‌کولای؛ آسیب جنینی؛ آنتی‌اکسیدان

مراجع

• Alfonso, L., Arnaiz, A., Alvarez, F., Qi, B., Diez-Pardo, J., Vallis-I-Soler, A., et al. (1996). Lung hypoplasia and surfactant system immaturity induced in the fetal rat by prenatal exposure to nitrofen. Neonatology, 69­(2): 94-100.
• 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.
  • Rondo, P., Ferreira, R., Nogueira, F., Ribeiro, M., Lobert, H. and Artes, R. (2003). Maternal psychological stress and distress as predictors of low birth weight, prematurity and intrauterine growth retardation. European Journal of Clinical Nutrition, 57­(2): 266-272.
    • Savitha, S., Tamilselvan, J., Anusuyadevi, M. and Panneerselvam, C. (2005). Oxidative stress on mitochondrial antioxidant defense system in the aging process: role of DL-alpha-lipoic acid and L-carnitine. Internationla Journal of Clinical Chemistry, 355(1-2): 173-180.
• Silver, R.M., Edwin, S.S., Trautman, M.S., Simmons, D.L., Branch, D.W., Dudley, D.J., et al. (1995). Production of a newly recognized form of inducible cyclooxygenase (COX-2) in murine decidua in response to lipopolysaccharide. Journal of Clinical Investigation, 95(2): 725-731.
• Silver, R.M., Edwin, S.S., Umar, F., Dudley, D.J., Branch, D.W. and Mitchell, M.D. (1997). Bacterial lipopolysaccharide-mediated murine fetal death: The role of interleukin-1. American Journal of Obstetrics and Gynecology, 176­(3): 544-549.
• Talge, N.M., Neal, C. and Glover, V. (2007). Antenatal maternal stress and long-term effects on child neurodevelopment: How and why? Journal of Child Psychology and Psychiatry, 48(3-4): 245-261.
• Thébaud, B., Tibboel, D., Rambaud, C., Mercier, J.C., Bourbon, J.R., Dinh-Xuan, A.T., et al. (1999). Vitamin A decreases the incidence and severity of nitrofen-induced congenital diaphragmatic hernia in rats. American Journal of Physiology-Lung Cellular and Molecular Physiology, 277­(2): L423-L429.
• Welberg, L.A. and Seckl, J.R. (2001). Prenatal Stress, Glucocorticoids and the programming of the brain. Journal of Neuroendocrinology, 13­(2): 113-128.
• Xu, D.X., Chen, Y.H., Wang, H., Zhao, L., Wang, J.P. and Wei, W. (2006). Tumor necrosis factor alpha partially contributes to lipopolysaccharide-induced intra-uterine fetal growth restriction and skeletal development retardation in mice. Toxicology Letters, 163­(1): 20-29.
• Xu, D.X., Chen, Y.H., Zhao, L., Wang, H. and Wei, W. (2006). Reactive oxygen species are involved in lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation in mice. American Journal of Obstetrics and Gynecology, 196(6): 1714-1707.
• Yuan-Hua, C.H., De-Xiang, X., Lei, Z.H., Hua, W., Jian-Ping, W., Wei, W., et al. (2006). Ascorbic acid protects against lipopolysaccharide-induced intra-uterine fetal death and intra-uterine growth retardation in mice. Toxicology, 217(1): 39-45.
• Zobali, F., Avci, A., Canbolat, O. and Karasu, Ç. (2002). Effects of vitamin A and insulin on the antioxidative state of diabetic rat heart: A comparison study with combination treatment. Cell Biochemistry and Function, 20­(2): 75-80.