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

نوع مقاله: علمی پژوهشی

نویسندگان

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.

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


عنوان مقاله [English]

The role of vitamin A in preventing fetal injuries caused by injection of Escherichia coli lipopolysaccharide in the rat

نویسندگان [English]

  • Aref Delkhosh 1
  • masoud delashoub 2
  • M. Khakpour 3
1 - D.V.M. Graduate, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
2 Assistant Professor, Department of Basic Sciences , Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
3 Assistant Professor, Department of Pathobiology, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
چکیده [English]

Lipopolysaccharides (LPS) induce adverse fetal development including intrauterine growth retardation (IUGR), intrauterine fetal death (IUFD), embryonic resorption and preterm delivery which are all related to LPS-induced oxidative stress.  This study aimed to investigate the protective role of vitamin A against LPS induced fetal defects in the rat. In this study, 48 pregnant female rats were divided into 4 groups. On days 15 to 17 of pregnancy, 75 mg/kg of E. coli LPS was injected intraperitoneally in groups 1 and 2 the second and third groups received 100 mg/kg of vitamin A intramuscularly a week before injection of LPS. The fourth group was the control group and placebo was injected to simulate injection stress. On the 18th day, all rats were euthanized. The number of live and dead fetuses and resorption sites was counted. Live fetuses in each litter were weighed, crown-rump and tail lengths measured and skeletal development was evaluated. In addition, maternal liver, placenta, and fetal liver samples were excised for measurement of MDA and GSH contents. The results showed that administration of LPS significantly increased fetal mortality, decreased fetal weight and crown-rump and tail lengths of live fetuses and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges and supraoccipital bone. Our study showed that co-treatment of vitamin A and LPS could decrease LPS induced defects and improve injuries indicating the preventive effects of vitamin A against LPS induced injuries during fetal development.

کلیدواژه‌ها [English]

  • Vitamin A
  • Lipopolysaccharide
  • Escherichia coli‌
  • Fetal injury
  • Antioxidant
  • 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.