Skip to main content
Erschienen in: Archives of Gynecology and Obstetrics 3/2012

01.03.2012 | Maternal-Fetal Medicine

Elevated cardiac oxidative stress in newborn rats from mothers treated with atosiban

verfasst von: Yavuz Simsek, Onder Celik, Abdullah Karaer, Ercan Yılmaz, Mehmet Gul, Elif Ozerol, Sedat Bilgic, Nilufer Celik

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 3/2012

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The purpose of this study was to evaluate the cardiac and cerebral oxidative stress in the offspings of pregnant rats treated with oxytocin antagonist atosiban.

Methods

Experimentally naive, adult female Wistar-albino rats (200–250 g) were mated with adult male rats for copulation. After confirming pregnancy, eight gravid rats were then randomly assigned into two equal groups. The animals were treated from days 15 to 20 of gestation. One group acted as a control group, and received intraperitoneal (i.p.) injections of saline in a daily dose volume of 6 mg/kg/day. The second group received 6 mg/kg/day i.p. atosiban. On day 21 of gestation, pups were delivered by cesarean. The heart and brain tissues of the newborn rats were dissected and sent for the measurement of total oxidant status, total antioxitant status and oxidative stress index.

Results

There was no significant difference in birthweight or in the number of pups between two groups. Newborns from atosiban-treated mothers showed significantly increased oxidative stress in the plasma and heart tissue than that of controls which was confirmed by histological examination (P < 0.05). Oxidative stress parameters and histopathological results of the brain tissues of newborns were similar between two groups (P > 0.05).

Conclusion

Oxytocin receptor blockage for the treatment of premature delivery may be associated with increased fetal morbidity and mortality secondary to the elevated oxidative stress in the heart of the newborns.
Literatur
1.
Zurück zum Zitat Ananth CV, Vintzileos AM (2006) Epidemiology of preterm birth and its clinical subtypes. J Matern Fetal Neonatal Med 19:773–782PubMedCrossRef Ananth CV, Vintzileos AM (2006) Epidemiology of preterm birth and its clinical subtypes. J Matern Fetal Neonatal Med 19:773–782PubMedCrossRef
2.
Zurück zum Zitat Sehdev HM, Abbasi S, Robertson P, Fisher L, Marchiano DA, Gerdes JS, Ludmir J (2004) The effects of the time interval from antenatal corticosteroid exposure to delivery on neonatal outcome of very low birth weight infants. Am J Obstet Gynecol 191:1409–1413PubMedCrossRef Sehdev HM, Abbasi S, Robertson P, Fisher L, Marchiano DA, Gerdes JS, Ludmir J (2004) The effects of the time interval from antenatal corticosteroid exposure to delivery on neonatal outcome of very low birth weight infants. Am J Obstet Gynecol 191:1409–1413PubMedCrossRef
3.
Zurück zum Zitat Purdy IB, Wiley DJ (2004) Perinatal corticosteroids: a review of research. Part I: antenatal administration. Neonatal Netw 23:15–30PubMedCrossRef Purdy IB, Wiley DJ (2004) Perinatal corticosteroids: a review of research. Part I: antenatal administration. Neonatal Netw 23:15–30PubMedCrossRef
4.
Zurück zum Zitat Blumenfeld YJ, Lyell DJ (2009) Prematurity prevention: the role of acute tocolysis. Curr Opin Obstet Gynecol 21:136–141PubMedCrossRef Blumenfeld YJ, Lyell DJ (2009) Prematurity prevention: the role of acute tocolysis. Curr Opin Obstet Gynecol 21:136–141PubMedCrossRef
5.
Zurück zum Zitat Moutquin JM, Sherman D, Cohen H, Mohide PT, Hochner-Celnikier D, Fejgin M, Liston RM, Dansereau J, Mazor M, Shalev E, Boucher M, Glezerman M, Zimmer EZ, Rabinovici J (2000) Double-blind, randomized, controlled trial of atosiban and ritodrine in the treatment of preterm labor: a multicenter effectiveness and safety study. Am J Obstet Gynecol 183:1191–1199CrossRef Moutquin JM, Sherman D, Cohen H, Mohide PT, Hochner-Celnikier D, Fejgin M, Liston RM, Dansereau J, Mazor M, Shalev E, Boucher M, Glezerman M, Zimmer EZ, Rabinovici J (2000) Double-blind, randomized, controlled trial of atosiban and ritodrine in the treatment of preterm labor: a multicenter effectiveness and safety study. Am J Obstet Gynecol 183:1191–1199CrossRef
6.
Zurück zum Zitat Romero R, Sibai BM, Sanchez-Ramos L, Valenzuela GJ, Veille JC, Tabor B, Perry KG, Varner M, Goodwin TM, Lane R, Smith J, Shangold G, Creasy GW (2000) An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue. Am J Obstet Gynecol 182:1173–1183PubMedCrossRef Romero R, Sibai BM, Sanchez-Ramos L, Valenzuela GJ, Veille JC, Tabor B, Perry KG, Varner M, Goodwin TM, Lane R, Smith J, Shangold G, Creasy GW (2000) An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue. Am J Obstet Gynecol 182:1173–1183PubMedCrossRef
7.
Zurück zum Zitat Valenzuela GJ, Sanchez-Ramos L, Romero R, Silver HM, Koltun WD, Millar L, Hobbins J, Rayburn W, Shangold G, Wang J, Smith J, Creasy GW (2000) Maintenance treatment of preterm labor with the oxytocin antagonist atosiban. The Atosiban PTL-098 Study Group. Am J Obstet Gynecol 182:1184–1190PubMedCrossRef Valenzuela GJ, Sanchez-Ramos L, Romero R, Silver HM, Koltun WD, Millar L, Hobbins J, Rayburn W, Shangold G, Wang J, Smith J, Creasy GW (2000) Maintenance treatment of preterm labor with the oxytocin antagonist atosiban. The Atosiban PTL-098 Study Group. Am J Obstet Gynecol 182:1184–1190PubMedCrossRef
8.
Zurück zum Zitat French/Australian Atosiban Investigators Group (2001) Treatment of preterm labor with the oxytocin antagonist atosiban: a double-blind, randomized, controlled comparison with salbutamol. Eur J Obstet Gynecol Reprod Biol 98:177–185CrossRef French/Australian Atosiban Investigators Group (2001) Treatment of preterm labor with the oxytocin antagonist atosiban: a double-blind, randomized, controlled comparison with salbutamol. Eur J Obstet Gynecol Reprod Biol 98:177–185CrossRef
9.
Zurück zum Zitat Baumgartner T, Heinrichs M, Vonlanthen A, Fischbacher U, Fehr E (2008) Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron 58:639–650PubMedCrossRef Baumgartner T, Heinrichs M, Vonlanthen A, Fischbacher U, Fehr E (2008) Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron 58:639–650PubMedCrossRef
10.
Zurück zum Zitat Yoshida M, Takayanagi Y, Inoue K, Kimura T, Young LJ, Onaka T, Nishimori K (2009) Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice. J Neurosci 29:2259–2271PubMedCrossRef Yoshida M, Takayanagi Y, Inoue K, Kimura T, Young LJ, Onaka T, Nishimori K (2009) Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice. J Neurosci 29:2259–2271PubMedCrossRef
11.
Zurück zum Zitat Slattery DA, Neumann ID (2008) No stress please! Mechanisms of stress hyporesponsiveness of the maternal brain. J Physiol 586:377–385PubMedCrossRef Slattery DA, Neumann ID (2008) No stress please! Mechanisms of stress hyporesponsiveness of the maternal brain. J Physiol 586:377–385PubMedCrossRef
12.
Zurück zum Zitat Valenzuela GJ, Craig J, Bernhardt MD, Holland ML (1995) Placental passage of the oxytocin antagonist atosiban. Am J Obstet Gynecol 172:1304–1306PubMedCrossRef Valenzuela GJ, Craig J, Bernhardt MD, Holland ML (1995) Placental passage of the oxytocin antagonist atosiban. Am J Obstet Gynecol 172:1304–1306PubMedCrossRef
13.
Zurück zum Zitat Malek A, Blann E, Mattison DR (2006) Human placental transport of oxytocin. J Matern Fetal Med 5:245–255CrossRef Malek A, Blann E, Mattison DR (2006) Human placental transport of oxytocin. J Matern Fetal Med 5:245–255CrossRef
14.
Zurück zum Zitat Zellers JE, Davis CC, Oldham JW, Mackey MJ, Szot RJ (1996) Subcutaneous developmental toxicity study of RWJ-22164-021 (atosiban) in female Crl:CD®B.R., VAF/Plus® rats. Internal report no. 382520:1-DS-94307. RW Johnson Pharmaceutical Research Institute, Raritan, NJ Zellers JE, Davis CC, Oldham JW, Mackey MJ, Szot RJ (1996) Subcutaneous developmental toxicity study of RWJ-22164-021 (atosiban) in female Crl:CD®B.R., VAF/Plus® rats. Internal report no. 382520:1-DS-94307. RW Johnson Pharmaceutical Research Institute, Raritan, NJ
15.
Zurück zum Zitat Moosman B, Behl C (2002) Secretory peptide hormones are biochemical antioxidants: structure–activity relationship. Mol Pharmacol 61:260–268CrossRef Moosman B, Behl C (2002) Secretory peptide hormones are biochemical antioxidants: structure–activity relationship. Mol Pharmacol 61:260–268CrossRef
16.
Zurück zum Zitat Cetinel S, Hancioğlu S, Sener E, Uner C, Kiliç M, Sener G, Yeğen BC (2010) Oxytocin treatment alleviates stress-aggravated colitis by a receptor-dependent mechanism. Regul Pept 25(160):146–152CrossRef Cetinel S, Hancioğlu S, Sener E, Uner C, Kiliç M, Sener G, Yeğen BC (2010) Oxytocin treatment alleviates stress-aggravated colitis by a receptor-dependent mechanism. Regul Pept 25(160):146–152CrossRef
17.
Zurück zum Zitat Dusunceli F, Iseri SO, Ercan F, Gedik N, Yegen C, Yegen BC (2008) Oxytocin alleviates hepatic ischemia–reperfusion injury in rats. Peptides 29:1216–1222PubMedCrossRef Dusunceli F, Iseri SO, Ercan F, Gedik N, Yegen C, Yegen BC (2008) Oxytocin alleviates hepatic ischemia–reperfusion injury in rats. Peptides 29:1216–1222PubMedCrossRef
18.
Zurück zum Zitat Tugtepe H, Sener G, Biyikli NK, Yuksel M, Cetinel S, Gedik N, Yegen BC (2007) The protective effect of oxytocin on renal ischemia/reperfusion injury in rats. Regul Pept 140:101–108PubMedCrossRef Tugtepe H, Sener G, Biyikli NK, Yuksel M, Cetinel S, Gedik N, Yegen BC (2007) The protective effect of oxytocin on renal ischemia/reperfusion injury in rats. Regul Pept 140:101–108PubMedCrossRef
19.
Zurück zum Zitat Iseri SO, Gedik IE, Erzik C, Uslu B, Arbak S, Gedik N, Yegen BC (2008) Oxytocin ameliorates skin damage and oxidant gastric injury in rats with thermal trauma. Burns 34:361–369PubMedCrossRef Iseri SO, Gedik IE, Erzik C, Uslu B, Arbak S, Gedik N, Yegen BC (2008) Oxytocin ameliorates skin damage and oxidant gastric injury in rats with thermal trauma. Burns 34:361–369PubMedCrossRef
20.
Zurück zum Zitat Iseri SO, Sener G, Sağlam B, Gedik N, Ercan F, Yeğen BC (2005) Oxytocin ameliorates oxidative colonic inflammation by a neutrophil-dependent mechanism. Peptides 26:483–491PubMedCrossRef Iseri SO, Sener G, Sağlam B, Gedik N, Ercan F, Yeğen BC (2005) Oxytocin ameliorates oxidative colonic inflammation by a neutrophil-dependent mechanism. Peptides 26:483–491PubMedCrossRef
21.
Zurück zum Zitat Biyikli NK, Tugtepe H, Sener G, Velioglu-Ogünç A, Cetinel S, Midillioglu S, Gedik N, Yegen BC (2006) Oxytocin alleviates oxidative renal injury in pyelonephritic rats via a neutrophil-dependent mechanism. Peptides 27:2249–2257PubMedCrossRef Biyikli NK, Tugtepe H, Sener G, Velioglu-Ogünç A, Cetinel S, Midillioglu S, Gedik N, Yegen BC (2006) Oxytocin alleviates oxidative renal injury in pyelonephritic rats via a neutrophil-dependent mechanism. Peptides 27:2249–2257PubMedCrossRef
22.
Zurück zum Zitat Houshmand F, Faghihi M, Zahediasl S (2009) Biphasic protective effect of oxytocin on cardiac ischemia/reperfusion injury in anaesthetized rats. Peptides 30:2301–2308PubMedCrossRef Houshmand F, Faghihi M, Zahediasl S (2009) Biphasic protective effect of oxytocin on cardiac ischemia/reperfusion injury in anaesthetized rats. Peptides 30:2301–2308PubMedCrossRef
23.
Zurück zum Zitat Erel O (2005) A new automated colorimetric method for measuring total oxidant status. Clin Biochem 38:1103–1111PubMedCrossRef Erel O (2005) A new automated colorimetric method for measuring total oxidant status. Clin Biochem 38:1103–1111PubMedCrossRef
24.
Zurück zum Zitat Erel O (2004) A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 37:112–119PubMedCrossRef Erel O (2004) A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 37:112–119PubMedCrossRef
25.
Zurück zum Zitat Harma M, Harma M, Erel O (2003) Increased oxidative stress in patients with hydatidiform mole. Swiss Med Wkly 133:563–566PubMed Harma M, Harma M, Erel O (2003) Increased oxidative stress in patients with hydatidiform mole. Swiss Med Wkly 133:563–566PubMed
26.
Zurück zum Zitat Jankowski M, Hajjar F, Kawas SA, Mukaddam-Daher S, Hoffman G, McCann SM, Gutkowska J (1998) Rat heart: a site of oxytocin production and action. Proc Natl Acad Sci USA 24(95):14558–14563CrossRef Jankowski M, Hajjar F, Kawas SA, Mukaddam-Daher S, Hoffman G, McCann SM, Gutkowska J (1998) Rat heart: a site of oxytocin production and action. Proc Natl Acad Sci USA 24(95):14558–14563CrossRef
27.
Zurück zum Zitat Gutkowska J, Jankowski M, Mukaddam-Daher S, McCann SM (2000) Oxytocin is a cardiovascular hormone. Braz J Med Biol Res 33:625–633PubMedCrossRef Gutkowska J, Jankowski M, Mukaddam-Daher S, McCann SM (2000) Oxytocin is a cardiovascular hormone. Braz J Med Biol Res 33:625–633PubMedCrossRef
28.
Zurück zum Zitat Jankowski M, Wang D, Hajjar F, Mukaddam-Daher S, McCann SM, Gutkowska J (2000) Oxytocin and its receptors are synthesized in the rat vasculature. Proc Natl Acad Sci USA 97:6207–6211PubMedCrossRef Jankowski M, Wang D, Hajjar F, Mukaddam-Daher S, McCann SM, Gutkowska J (2000) Oxytocin and its receptors are synthesized in the rat vasculature. Proc Natl Acad Sci USA 97:6207–6211PubMedCrossRef
29.
Zurück zum Zitat Iseri SO, Sener G, Saglam B, Gedik N, Ercan F, Yegen BC (2005) Oxytocin protects against sepsis-induced multiple organ damage: role of neutrophils. J Surg Res 126:73–81PubMedCrossRef Iseri SO, Sener G, Saglam B, Gedik N, Ercan F, Yegen BC (2005) Oxytocin protects against sepsis-induced multiple organ damage: role of neutrophils. J Surg Res 126:73–81PubMedCrossRef
30.
Zurück zum Zitat Houshmand F, Faghihi M, Saleh Z (2009) Biphasic protective effect of oxytocin on cardiac ischemia/reperfusion injury in anaesthetized rats. Peptides 30:2301–2308PubMedCrossRef Houshmand F, Faghihi M, Saleh Z (2009) Biphasic protective effect of oxytocin on cardiac ischemia/reperfusion injury in anaesthetized rats. Peptides 30:2301–2308PubMedCrossRef
31.
Zurück zum Zitat Gutkowska J, Jankowski M, Lambert C, Mukaddam-Daher S, Zingg H, McCann S (1997) Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors in the heart. Proc Natl Acad Sci USA 94:11704–11709PubMedCrossRef Gutkowska J, Jankowski M, Lambert C, Mukaddam-Daher S, Zingg H, McCann S (1997) Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors in the heart. Proc Natl Acad Sci USA 94:11704–11709PubMedCrossRef
32.
Zurück zum Zitat Christian MS, Hoberman AM, Foss JA (1995) Perinatal and postnatal reproduction study of RWJ-22164–021 administered subcutaneously to Crl:CD®BR, VAF/Plus® rats (Segment III evaluation). Includes postnatal “behavioral/functional” evaluation. Argus Research Laboratories Inc., Horsham Christian MS, Hoberman AM, Foss JA (1995) Perinatal and postnatal reproduction study of RWJ-22164–021 administered subcutaneously to Crl:CD®BR, VAF/Plus® rats (Segment III evaluation). Includes postnatal “behavioral/functional” evaluation. Argus Research Laboratories Inc., Horsham
33.
Zurück zum Zitat Fuchs AR, Romero R, Keefe D, Parra M, Oyarzun E, Behnke E (1991) Oxytocin secretion and human parturition: pulse frequency and duration increase during spontaneous labor in women. Am J Obstet Gynecol 165(5 Pt 1):1515–1523PubMed Fuchs AR, Romero R, Keefe D, Parra M, Oyarzun E, Behnke E (1991) Oxytocin secretion and human parturition: pulse frequency and duration increase during spontaneous labor in women. Am J Obstet Gynecol 165(5 Pt 1):1515–1523PubMed
34.
Zurück zum Zitat de Geest K, Thiery M, Piron-Possuyt G, Vanden Driessche R (1985) Plasma oxytocin in human pregnancy and parturition. J Perinat Med 13:3–13PubMedCrossRef de Geest K, Thiery M, Piron-Possuyt G, Vanden Driessche R (1985) Plasma oxytocin in human pregnancy and parturition. J Perinat Med 13:3–13PubMedCrossRef
35.
36.
Zurück zum Zitat Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E (2005) Oxytocin increases trust in humans. Nature 435:673–676PubMedCrossRef Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E (2005) Oxytocin increases trust in humans. Nature 435:673–676PubMedCrossRef
37.
Zurück zum Zitat Uvnas-Moberg K (1998) Antistress pattern induced by oxytocin. News Physiol Sci 13:22–25PubMed Uvnas-Moberg K (1998) Antistress pattern induced by oxytocin. News Physiol Sci 13:22–25PubMed
38.
Zurück zum Zitat Dawood MY, Wang CF, Gupta R, Fuchs F (1978) Fetal contribution to oxytocin in human labor. Obstet Gynecol 52:205–209PubMed Dawood MY, Wang CF, Gupta R, Fuchs F (1978) Fetal contribution to oxytocin in human labor. Obstet Gynecol 52:205–209PubMed
39.
Zurück zum Zitat Tyzio R, Cossart R, Khalilov I, Minlebaev M, Hübner CA, Represa A, Ben-Ari Y, Khazipov R (2006) Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery. Science 314:1788–1792PubMedCrossRef Tyzio R, Cossart R, Khalilov I, Minlebaev M, Hübner CA, Represa A, Ben-Ari Y, Khazipov R (2006) Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery. Science 314:1788–1792PubMedCrossRef
Metadaten
Titel
Elevated cardiac oxidative stress in newborn rats from mothers treated with atosiban
verfasst von
Yavuz Simsek
Onder Celik
Abdullah Karaer
Ercan Yılmaz
Mehmet Gul
Elif Ozerol
Sedat Bilgic
Nilufer Celik
Publikationsdatum
01.03.2012
Verlag
Springer-Verlag
Erschienen in
Archives of Gynecology and Obstetrics / Ausgabe 3/2012
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-011-2069-5

Weitere Artikel der Ausgabe 3/2012

Archives of Gynecology and Obstetrics 3/2012 Zur Ausgabe

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.