Oxidative stress in dogs during mid-gestation abortion: Fetal and maternal antioxidant alterations with clinical and hematological features

Published: Jul 10, 2022
Pregnancy termination Malondialdehyde Reduced Glutathione Prostaglandin Aglepristone Dog
Gozde Özalp
Z Gül
N Seyidoglu
L Büyükuysal

The present study aimed to evaluate the GSH and MDA levels in dog’s serum and vital organs of aborted fetuses, after application of two abortifacient. Animals of group I (n = 6) were treated twice with subcutaneous injection of 10 mg/kg aglepristone and group II (n = 3) received prostaglandin F2α at a dose of 125 μg/kg every 12 hours until abortion process completed. Hematologic examinations and sedimentation rates were performed of bitches. The duration between first occurrence of vaginal discharge to first expulsion of fetuses ranged between 14-29 hours (mean: 22.6±5.5 h) and 24-33 hours in group I and II, respectively. Both treatments significantly increased the serum MDA levels (P<0.01); however aglepristone increased the MDA levels throughout the study, prostaglandin enhanced plasma MDA levels only on day 1. GSH levels were significantly lower in aglepristone-treated bitches than prostaglandin-treated animals (P<0.05). The treatments resulted similar MDA levels in liver and heart tissues (P>0.05). GSH levels in kidney, muscle and heart tissues did not differ between groups (P>0.05), aglepristone resulted reduced GSH levels in liver tissue (P<0.05). High MDA levels could be evaluated as a useful marker for fetal suffering in pregnancy controls. The MDA and GSH levels, measured in vital organs of fetuses, could suggest possible toxic effects of abortifacients in newborns, as both medical agents are being used in parturition induction.

Article Details
  • Section
  • Research Articles
Download data is not yet available.
Acaroz U, Ince S, Arslan-Acaroz D, Gurler Z, Kucukkurt I, Demirel HH,
Ozancan Arslan H, Varol N, Zhu K (2018) The ameliorative effects
of boron against acrylamide-induced oxidative stress, inflammatory
response, and metabolic changes in rats. Food and Chemical Toxicology
: 745-52.
Arslan HO, Herrera C, Malama E, Siuda M, Leiding C, Bollwein H
(2019) Effect of the addition of different catalase concentrations to
a TRIS-egg yolk extender on quality and in vitro fertilization rate of
frozen-thawed bull sperm. Cryobiology. 91:40-52.
Athar M, Abdulla H, Sultana S, Favier A, Pero R (1993) Free radicals and
trace elements. J Trace Elem Exp Med 6:65-73.
Baan M, Taverne MA, Kooistra HS, De Gier J, Dieleman SJ, Okkens AC
(2005) Induction of parturition in the bitch with the progesterone receptor
blocker aglépristone. Theriogenology 63: 1958-72.
Casanueva E, Viteri FE (2003) Iron and oxidative stress in pregnancy.
Journal of Nutrition 133: 1700-8.
Cetin Y, Macun HC, Beceriklisoy HB, Schӓfer-Somi S, Aslan S (2000)
Intravaginal application of misoprostol improves pregnancy termination
with cabergoline and alfaprostol in dogs. Berl Munch Tierarztl
Wochensch 123: 236-42.
Cindriva - Davies T, Yung HW, Johns J, Spatic-Boskovic O, Korolchuk S,
Jauniaux E, Burton GJ, Charnock-Jones DS (2007) Oxidative stress,
gene expression, and protein changes induced in the human placenta
during labor. Am J Pathol 171: 1168-79.
Concannon PW, Hansel W (1997) Prostaglandin F2alpha induced luteolysis,
hypothermia, and abortions in beagle bitches. Prostaglandins
Corrada Y, García P, De La Sota PE, Huzman M, Landoni MF, Gobello
C (2005) Decrease of body temperature after aglepristone in bitches.
Anim Reprod Sci 87: 295-99.
Corrada Y, Rodríguez R, Tortora M, Arias D, Gobello C (2006) A combination
of oral cabergoline and double cloprostenol injections to
produce third-quarter gestation termination in the bitch. J Am Anim
Hosp Assoc 42:366-70.
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:
Feldman EC, Davidson AP, Nelson RW, Nyland TG, Munro C (1993)
Prostaglandin induction of abortion in pregnant bitches after misalliance.
J Am Vet Med Assoc 202: 1855-58.
Fieni F, Marnet PG, Martal J, Siliart B, Touzeau N, Bruyas JF, Tainturier
D. Comparison of two protocols with a progesterone antagonist aglepristone
(RU534) to induce parturition in bitches (2001) J Reprod
Fertil Suppl 57: 237-42.
Fontbonne A, Fontaine E, Lévy X, Bachellerie R, Bernex F, Atam-Kas-sigadou S, Guffroy M, Leblond E, Briant E (2009) Induction of parturition
with aglepristone in various sized bitches of different breeds.
Reprod Domest Anim 44: 170-73.
Forman HJ, Zhang H, Rinna A (2009). Glutathione: overview of its protective
roles, measurement, and biosynthesis. Mol Aspects Medicine
: 1-12.
Galac S, Kooistra HS, Butinar J, Bevers MM, Dieleman SJ, Voorhout G,
Okkens AC (2000) Termination of mid-gestation pregnancy in bitches
with aglepristone, a progesterone receptor antagonist. Theriogenology
Georgiev P, Wehrend A (2006) Mid-gestation pregnancy termination by
the progesterone antagonist aglepristone in queens. Theriogenology
: 1401-06.
Gleich GJ (2000) Mechanisms of eosinophil-associated inflammation. J
Allergy Clin Immunol 105:651-63.
Gleich GJ, Adolphson CR, Leiferman KM (1993) The biology of the eosinophilic
leukocyte. Annu Rev Med 44: 85-101.
Gobello C, Castex G, Corrada Y, Klima L, De La Sota RL, Rodriguez R
(2002) Use of prostaglandins and bromocriptine mesylate for pregnancy
termination in bitches. J Am Vet Med Assoc 220: 1017-19.
Gouon-Evans V, Rothenberg ME, Pollard JW (2000) Postnatal mammary
gland development requires macrophages and eosinophils. Development
: 2269-82.
Halliwell B (1997) Antioxidants and human disease. A general introduction.
Nutr Rev 55: 49-52.
Hameed MA, Waqas S (2006) Physiological basis and clinical utility of
erythrocyte sedimentation rate. Pak J Med Sci 22: 214-18.
Harma M, Harma M, Kocyigit A (2004) Comparison of protein carbonyl
and total plasma thiol concentrations in patients with complete hydatidiform
mole with those in healthy pregnant women. Acta Obstetricia
et Gynecologica Scandinavica 83: 857-60.
Hayden RE, Paniello RC, Yeung CS, Bello SL, Dawson SM (1987) The
effect of glutathione and vitamins A, C, and E on acute skin flap survival.
Laryngoscope 97: 1176-79.
Hori T, Akikawa T, Kawakami E, Tsutsui T (2002) Fenprostalene-induced
abortion in bitches. J Vet Med Sci 64:993-98.
Issa AM, Hassan BG, Gatea AK (2012) Relationship of Nitric Oxide and
Malondialdehyde to Miscarriage. Medical Journal of Babylon 9: 777-
Jackson AL, Chen R, Loeb LA (1998) Induction of microsatellite instability
by oxidative DNA damage. Proc Natl Acad Sci 12468-473.
Jain NC (1986) Schalm’s Veterinary heamatology. Lea and Febiger: Philadelphia;
Kaya D, Küçükaslan I, Ağaoğlu AR, Ay SS, Schäfer-Somi S, Emre B, Bal
Y, Einspanier A,Gürcan IS, Gültiken N, Aslan S (2014) The effects of
aglepristone alone and in combination with cloprostenol on hormonal
values during termination of mid-term pregnancy in bitches. Anim
Reprod Sci 146:210-17.
Khan S, Khan S, Khan MM, Alam R, Khan A (2019) Estimation of the
status of MDA levels and SOD activity in pregnant women. Biochem
Cell Arch 19: 169-81.
Kolusarı A, Kurdoglu M, Yıldızhan R, Adalı E, Edirne T, Cebi A, Demir
H, Yörük IH (2008) Catalase activity, serum trace element and heavy
metal concentrations, and vitamin A, D and E levels in pre-eclampsia.
J Int Med Res 36: 1335 - 41.
Konuk T (1981) Pratik Fizyoloji. Ankara Üniversitesi Veteriner Fakültesi
Yayınları: Ankara Üniversitesi Basımevi; Ankara.
Kowalewski MP, Beceriklisoy HB, Pfarrer C, Aslan S, Kindahl H,
Küçükarslan İ, Hoffmann B (2009) Canine Placenta: A source of
prepartal prostaglandins during normal and antiprogestin-induced
parturition. Reproduction 139: 655-64.
Krieger TR, Loch-Caruso R (2001) Antioxidants prevent gamma- hexachlorocyclohexane-
induced inhibition of rat myometrial gap junctions
and contractions. Biol Reprod 64: 537-47.
Lewis SM (1980) Erythrocyte sedimentation rate and plasma viscosity.
Association of Clinical Pathologists Broadsheet 94: 1-7.
Liu AX, He WH, Yin LJ, Lv PP, Zhang Y, Sheng JZ, Leung PCK, Huang
HF (2011) Sustained endoplasmic reticulum stress as a cofactor of
oxidative stress in decidual cells from patients with early pregnancy
loss. J Clin Endocrinol Metab 96:493-97.
Luvoni GC, Grioni A (2000) Determination of gestational age in medium
and small size bitches using ultrasonographic fetal measurements.
Journal of Small Animal Practice 41: 292-94.
Lowlier EA, Sovereign JHM, Helleman PW (1977) Het mechanisme van
de bezinkingssnelheid van erythrocyten. Ned T Geneeskunde 121:
Mehmetoglu I, Kart A, Caglayan O, Çapar M, Gökçe R (2002) Oxidative
stress mothers and their newborns in different types of labour. Turk J
Med Sci 32: 427-29.
Mongelli M, Wang CC, Wang W (1997) Oxygen free radical activity in
the second stage of labour. Acta Obstet Gynecol Scand 76: 765-68.
Oettlé EE (1982) Clinical experience with prostaglandin F2 alpha THAM
as a luteolytic agent in pregnant and non-pregnant bitches. J S Afr Vet
Assoc 53: 239-42.
Onclin K, Silva LDM, Verstegen JP (1995) Termination of unwanted
pregnancy in dogs with the dopamine agonist, cabergoline, combination
with a synthetic analog of PGF2α, either cloprostenol or alphaprostol.
Theriogenology 43: 813-22.
Onclin K, Verstegen JP (1996) Practical use of a combinatton of a dopamine
agonist and a synthetic prostaglandin analogue to terminate
unwanted pregnancy in dogs. J Small Anim Prac 37:211-16.
Onclin K, Verstegen JP (1999) Comparisons of different combinations of
analogues of PGF2 α and dopamine agonists for the termination of
pregnancy in dogs. Vet Rec 144: 416-19.
Papa PC, Hoffmann B (2011) The corpus luteum of the dog: Source and
target of steroid hormones? Reprod Dom Anim 46: 750-56.
Perrone S, Laschi E, Buonocore G (2019) Biomarkers of oxidative stress
in the fetus and in the newborn. Free Radic Biol Med 142: 23-31.
Petterson CH, Tidholm A (2009) Safety and efficacy of mid-term pregnancy
termination using aglepristone in dogs. J Small Anim Pract 50:
Pilz J, Meineke I, Gleiter CH (2000) Measurement of free and bound
malondialdehyde in plasma by high-performance liquid chromatography
as the 2,4-dinitrophenylhydrazine derivative. J Chromatogr B
Biomed Sci Appl 742: 315-25.
Romagnoli SE, Cela M, Camillo F (1991) Use of prostaglandin F2 α for
early pregnancy termination in the mismated bitch. Vet Clin North
Am Small Anim Pract 21: 487-99.
Ross R, Klebanoff SJ (1966) The eosinophilic leukocyte. Fine structure
studies of changes in the uterus during the estrous cycle. J Exp Med
: 653-60.
Rogers MS, Mongelli M, Tsang KH, Wang CC (1999) Fetal and maternal
levels of lipid peroxides in term pregnancies. Acta Obstet Gynecol
Scand 78: 120-24.
Shille VM, Dorsey D, Thatcher MJ (1984) Induction of abortion in the
bitch with a synthetic prostaglandin analog. Am J Vet Res 45:1295-
Soma-Pillay P, Nelson-Piercy C, Tolppanen H, Mebazaa A (2016) Physiological
changes in pregnancy. Cardiovasc J Afr 27: 89-94.
Szczubiał M, Kankofer M, Dąbrowski R, Bochniarz M, Urban-Chmiel
R (2015) Assessment of lipid and protein peroxidation markers in
non-pregnant and pregnant female dogs. Polish Journal of Veterinary
Sciences 18: 171-79.
Turgut G, Enli Y, Kaptanoğlu B, Turgut S, Genç O (2006) Changes in the
levels of MDA and GSH in mice serum, liver and spleen after aluminum
administration. Eastern Journal of Medicine 11: 7-12.
Van Bladeren PJ (2000) Glutathione conjugation as a bioactivation reaction.
Chem Biol Interact 129:61-76.
Vannucchi CI, Jordao AA, Vannucchi H (2007) Antioxidant compounds
and oxidative stress in female dogs during pregnancy. Research in
Veterinary Science 83: 188-93.
Vatan Ö, Bağdaş D, Cinkiliç N, Wehrend A, Özalp GR (2015) Genotoxic
and cytotoxic effects of the aglepristone, a progesteron antagonist, in
mid-gestation pregnancy termination in rabbits. Kafkas Univ Vet Fak
Derg 21: 241-46.
Yusrawati, Pebrina M, Herman RB (2017) Differences in Malondialdehyde
and Catalase Activity Levels Between Abortion and Normal Pregnancy.
J Med Sci 17: 22-5.
Wanke M, Loza ME, Monachesi N, Concannon P (1997) Clinical use of
dexamethasone for termination of unwanted pregnancy in dogs. J Reprod
Fertil Suppl 51: 233-38.
Zone M, Wanke M, Rebuelto M, Loza M, Mestre J, Duchene A, Concannon
P (1995) Termination of pregnancy in dogs by oral administration
of dexamethasone. Theriogenology 43: 487-94.
Most read articles by the same author(s)