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Endotoxin-induced Abortion in Early Pregnant Gilts and its Prevention by Flunixin Meglumine

Endotoxin-inducerad abort hos tidigt dräktiga gyltor och hur den kan förebyggas med flunixin meglumin

Acta Veterinaria Scandinavica volume 31, pages 347–358 (1990)Cite this article

Abstract

The objective of the study was to examine the effect of endotoxin on early pregnancy in gilts and to test the potential of flunixin meglumine (FM), a cyclooxygenase inhibitor, to counteract abortifacient action of the endotoxin. Ten gilts at 30 days gestation were used in the experiment. Eight were injected with lipopolysaccharide (LPS) of Salmonella typhimurium, while 2 were treated with 500 µg cloprostenol (CP). Six of the LPS-injected gilts were treated with a total of 4 mg/kg body weight FM in 2 different dose regimens. Clinical observations were recorded and plasma levels of 15-keto-13, 14-dihydro-PGF2α, progesterone and estrone sulfate (ES) were determined with radioimmunoassay.

LPS induced typical signs of endotoxemia and a monophasic fever in all LPS-treated gilts. No antipyretic effect of FM was observed. The CP-treated gilts aborted within 34 h as did the gilts treated by LPS only. Of the 6 LPS + FM-treated gilts, 1 aborted within 34 h, while 5 maintained gestation. These were aborted about a week later by CP and the aborted fetuses anatomically examined. Two of the litters were lost (devoured by the dams), 2 showed no signs of earlier death and 1 showed extensive fetal death.

The PGF2α metabolite concentrations increased at least 10 fold immediately after the LPS injection. Progesterone plasma concentration decreased rapidly. A 5–10 fold increase in the plasma metabolite levels accompanied all abortions. CP caused no immediate change in the PGF2α metabolite levels, but the abortion-related response was similar to that in LPS-injected gilts. In the FM-treated gilts, the LPS-induced PGF2α metabolite response was rudimentary and the progesterone decrease temporary in nonaborting gilts. The elevated concentrations of ES decreased within 48 h in gilts aborting at 30 days gestation, while in nonaborting gilts a slow, graduate decrease of ES occurred within 3–5 days of the LPS injection. These results indicate that FM apparently suppressed LPS-induced prostaglandin synthesis and thus prevented luteolysis and abortion in early pregnant gilts.

Sammanfattning

Målsattningen med denna studie var att undersöka effekten av endotoxin på tidigt dräktiga gyltor och flunixin meglumins (FM) förmåga att motverka endotoxinets abortframkallande egenskaper. Flunixin är en hämmare av enzymet cyclooxygenas, som syntetiserar prostaglandiner och närstående föreningar. Tio gyltor som var i 30 dagars dräktighet användes i detta försök. Åtta djur injicerades med endotoxin (lipopolysackarid, LPS) från Salmonella typhimurium och 2 djur behandlades med 500 μg cloprostenol (CP). Sex av de LPS-behandlade djuren erhöll en total dos av flunixin om 4 mg/kg kroppsvikt via 2 olika behandlingsstrategier. Kliniska förändringar observerades och plasmanivåer av 15-keto-13, 14-dihydroprostaglandin (PG) PGF2α, progesteron och östronsulfat (ES) bestämdes med radioimmunologisk metodik.

LPS framkallade typiska tecken på endotoxinemi och en monofasisk feber hos alla LPS-behandlade djur. Ingen febernedsättande effekt av FM observerades. Djuren som behandlades med CP eller enbart LPS aborterade inom 34 tim. Av de 6 djuren som kombinationsbehandlades med LPS och FM, aborterade ett djur inom 34 tim, medan 5 vidmakthöll dräktigheten. Dessa fem djur aborterades en vecka senare med CP för att möjliggöra en makroskopisk undersökning av fostren. Två kullar förlorades pga att modern åt upp dem, 2 aborterades utan tecken på fosterskador och 1 kull uppvisade tydlig fosterdöd tydande på att endotoxinet hade haft negativ inverkan.

Blodplasmanivåerna av prostaglandinmetaboliten ökade 10-faldigt omedelbart efter LPS-injektionerna hos de 2 djur som erhöll enbart LPS och progesteron sjönk snabbt. I samband med aborterna syntes vidare end 5–10 faldig ökning i plasmanivåerna av prostaglandinmetaboliten. CP medförde inte någon omedelbar förändring i prostaglandinmetabolitnivåerna, men ett liknande svar syntes i samband med aborten som hos de LPS-inducerade djuren. I den FM-behandlade gruppen syntes endast en smärre ökning i prostaglandinmetaboliten och progesteronnivåerna uppvisade en overgående sänkning. Östronsulfat, som normalt ligger högt vid 30 dagars dräktighet, sjönk snabbt inom 48 tim hos gyltor som aborterade till skillnad mot icke-aborterade djur som uppvisade en langsam sankning av ES under loppet av 3–5 dagar.

Detta resultat tyder på att FM hämmar den LPS-inducerade prostaglandinsyntesen och således förhindras luteolys och abort hos tidigt dräktiga gyltor.

References

  • Bazer FW, First NL: Pregnancy and parturition. J. Anim. Sci. 1983, 57, suppl. 2, 425–460.

    Article  CAS  Google Scholar 

  • Bosu WTK, Edqvist L-E, Martinsson K, Johansson EDB: The effect of various dosages of lynesterol on the plasma levels of oestrogens and progesterone during the menstrual cycle in the rhesus monkey. Contraception 1976, 13, 677–684.

    Article  CAS  Google Scholar 

  • Bottoms GD, Fessier JF, Roesel DF, Moore AB, Frauenfelder HC: Endotoxin-induced hemodynamic changes in ponies: Effects of flunixin meglumine. Amer. vet. Res. 1981, 42, 1514–1518.

    CAS  Google Scholar 

  • Burrows GE: Therapeutic effect of phenylbutazone on experimental acute Escherichia coli endotoxemia in ponies. Amer. J. vet. Res. 1981, 142, 94–99.

    Google Scholar 

  • Cort N: A clinical study on the effect of a Gramnegative bacterial endotoxin and cloprostenol in nonpregnant and 60 days pregnant gilts. Anim. Reprod. Sci. 1986, 10, 133-145.

  • Cort N, Kindahl: The effect of a bacterial endotoxin or cloprostenol on the clinical status and hormonal levels in 80–100 days pregnant gilts. Acta vet. scand. 1986, 27, 145–158.

    Article  CAS  Google Scholar 

  • Cort N, Kindahl H, Einarsson S: The effect of a Gramnegative bacterial endotoxin and cloprostenol on the plasma levels of 15-keto-13, 14-dihy-dro-PGF2α progesterone, oestradiol-17β, oestrone sulphate and luteinizing hormone in non-pregnant and 60 days pregnant gilts. Anim. Reprod. Sci. 1986,10, 147–162.

  • Culbertson Jr R, Osburn BI: The biologic effects of bacterial endotoxin: A short review. Vet. Sci. Commun. 1980, 4, 3–13.

    CAS  Google Scholar 

  • Dennis SM: The effect of bacterial endotoxin on pregnancy. Vet. Bulletin 166, 36, 123–128.

  • First NL, Bosc M J: Proposed mechanisms controlling parturition and the induction of parturition in swine. J. Anim. Sci. 1979, 48, 1407–1421.

    Article  CAS  Google Scholar 

  • Fletcher JR, Herman CR, Remwell PW: Improved survival in endotoxemia with aspirin and indomethacin pretreatment. Surg Forum, 1976, 27, 11–12.

    CAS  PubMed  Google Scholar 

  • Flower RJ: Drugs which inhibit prostaglandin biosynthesis. Pharmacological Reviews 1974, 26, 33–67.

    CAS  PubMed  Google Scholar 

  • Guthrie HD, Polge C: Treatment of pregnant gilts with a prostaglandin analogue, cloprostenol, to control oestrus and fertility. J. Reprod. Fert. 1978, 52, 271–273.

    Article  CAS  Google Scholar 

  • Hardie EM, Rowlings CA, Shotts EB, Waltman DW, Rakich PM: Escherichia coli-induced lung and liver dysfunction in dogs: Effects of flunixin meglumine treatment. Amer. J. vet. Res. 1987, 48, 56–62.

    CAS  PubMed  Google Scholar 

  • Harper MJK, Skarnes RC: Inhibition of abortion and fetal death produced by endotoxin or prostaglandin F2α. Prostaglandins 1972, 2, 295–308.

    Article  CAS  Google Scholar 

  • Houdeshell GD, Hennessey PW: A new nonsteroidal, antiinflammatory analgesic for horses. J. Equine Med. surg. 1977, 1, 57–63.

    CAS  Google Scholar 

  • Kindahl H, Edqvist L-E, Granström E, Bane A: The release of prostaglandin F2α as reflected by 15-keto-13, 14-dihydroprostaglandin F2α in the peripheral circulation during normal luteolysis in heifers. Prostaglandins 1976, 11, 871–878.

    Article  CAS  Google Scholar 

  • Linderg AA, Sheldon GE, Svensson SB: Induction of endotoxin tolerance with nonpyrogenic 0-antigenic oligosaccharide-protein conjugates. Infect. Immun. 1983, 41, 888–895.

    Article  Google Scholar 

  • Moore JN, Hardee MM, Hardee GE: Modulation of arachidonic acid metabolism in endotoxic horses: Comparison of flunixin meglumine, phenylbutazone and a selective thromboxane synthetase inhibitor. Amer. J. vet. Res. 1986, 47, 110–113.

    CAS  PubMed  Google Scholar 

  • Odensvik K, Cort N, Basu S, Kindahl H: Effect of flunixin meglumine on prostaglandin F2α synthesis and metabolism in the pig. J. vet. Pharmacol. Therap. 1989, 12, (in press).

  • Podany J, Vanicek J, Stejskal J, Selének L: Induction of abortion with prostaglandin F2α in gilts and their subsequent fertility. Theriogenology 1982, 17, 393–400.

    Article  CAS  Google Scholar 

  • Rieder RF, Thomas L: Studies on the mechanisms involved in the production of abortion by endotoxin. J. Immunol. 1960, 84, 189–193.

    Google Scholar 

  • Roberts JS, Barcikowski B, Wilson L, Skarnes RC, McCracken JA: Hormonal and related factors affecting the release of prostaglandin F2α from the uterus. J. Ster. Biochem. 1975, 6, 1092–1097.

    Article  Google Scholar 

  • Robertson HA, King CJ: Plasma concentrations of progesterone, oestrone, oestradiol-17β and of oestrone sulphate in the pig at implantation, during pregnancy and at parturition. J. Reprod. Fert. 1974, 40, 133–141.

    Article  CAS  Google Scholar 

  • Rodriguez-Martinez H, Kunavongkrit A: Chronic venous catheterization for frequent blood sampling in unrestrained pigs. Acta vet. scand. 1983, 24, 318–320.

    Article  Google Scholar 

  • Skarnes RC, Brown SK, Huss SS, McCraken JA: Role of prostaglandin E in the biphasic fever response to endotoxin. J. exp. Med. 1981, 154, 1212–1224.

    Article  CAS  Google Scholar 

  • Svensson SB, Lindberg AA: Immunochemistry of Salmonella 0-antigens: Preparations of an octa-saccharide-bovine serum albumin immunogen representative of Salmonella serogroup B 0-antigen and characterization of the antibody response. J. Immunol. 1978, 120, 1750–1757.

    Google Scholar 

  • Turek JJ, Templeton B, Bottoms GD, Fessler JF: Flunixin meglumine attenuation of endotoxin-induced damage to the cardiopulmonary vascular endothelium of the pony. Amer. J. vet. Res. 1985, 46, 591–596.

    CAS  PubMed  Google Scholar 

  • Vernimb GD, Hennessey PW: Clinical studies on flunixin meglumine in the treatment of equine colic. J. Equine Med. Surg. 1977, 1, 111–116.

    Google Scholar 

  • Wang JT, Dunne HW, Griel LC, Hokanson JF, Murphy DM: Mortality, antibody development and viral persistence in porcine fetuses incubated in utero with SMEDI (Entero-) virus. Amer. J. vet. Res. 1973, 34, 785–788.

    CAS  PubMed  Google Scholar 

  • Wrathall AE, Wray C, Bailey J, Wells DE: Experimentally induced bacterial endotoxaemia and abortion in pigs. Brit. vet. J. 1978, 134, 225–230.

    Article  CAS  Google Scholar 

  • Wrathall AE: Mechanisms of porcine reproductive failure. Vet. Annual 1980, 20, 265–274.

    Google Scholar 

  • Wright K, Collins DC, Musey PI, Preedy JRK: A specific radioimmunoassay for estrone sulphate in plasma and urine without hydrolysis. J. clin. Endocr. Metab. 1978, 47, 1092–1098.

    Article  CAS  Google Scholar 

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  1. Department of Obstetrics and Gynaecology, College of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden

    Nicholas Cort & Hans Kindahl

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  1. Nicholas Cort
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  2. Hans Kindahl
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Cort, N., Kindahl, H. Endotoxin-induced Abortion in Early Pregnant Gilts and its Prevention by Flunixin Meglumine. Acta Vet Scand 31, 347–358 (1990). https://doi.org/10.1186/BF03547547

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Acta Veterinaria Scandinavica

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