Iranian Journal of Veterinary Surgery

Iranian Journal of Veterinary Surgery

Evaluation of Possible Effects of Hyoscine in Xylazine-Induced Fetal Death in Pregnant Rats

Document Type : Original Article

Authors
Mona Zohani-Ghayeni 1
Siamak Kazemi-Darabadi 1
Abolfazl Hajibemani 1
Ghasem Akbari 2
1 Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
2 Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
10.30500/ivsa.2023.379508.1330
Abstract
Although xylazine is widely used in domestic animals as a sedative, analgesic, and muscle relaxant, its side effects on the uterus prevent its utilization in pregnant animals or in embryo transfer. Although the effects of xylazine on increasing uterine contractions have been confirmed, no reliable report of fetal death due to xylazine administration has been published. Hyoscine is an anticholinergic medication that has antimuscarinic and antispasmodic effects in the uterine tissue of pregnant cattle during in vitro studies, therefore, we investigated if administration of xylazine in the last third of pregnancy could increase fetal death and if hyoscine could prevent its adverse effects. Twenty adult female rats, after mating with four adult male rats and confirming pregnancy, were randomly divided into two equal control and treatment groups. On the 18th day of pregnancy, the number of fetuses per rat was determined using ultrasonography. Rats in the treatment group received hyoscine (1 mg/kg, intraperitoneally) for 3 days. Subsequently, all rats were administered xylazine (10 mg/kg, intraperitoneally) for 3 days. On the 21st day of pregnancy, the number of living and dead fetuses was counted after laparotomy. Also, the weight and dimensions of the fetuses were measured. The results showed that although more fetuses lost their lives in the treatment group compared to the control group, the statistical difference in the percentage of fetal mortality in the two groups was not significant (p  0.05). In addition, the comparison of the mean weight, body length, and body width of living and dead fetuses in both groups showed that there was no statistically significant difference between these groups (p  0.05). It could be concluded that maternal xylazine intake in rats could cause about 18-25% of fetal mortality. However, the use of hyoscine to prevent fetal death induced by xylazine is not recommended.
Keywords
Xylazine
Fetal death
Rat
Hyoscine
Subjects
  1. Zeiler GE. A review of clinical approaches to antagonism of alpha2‐adrenoreceptor agonists in the horse. Equine Veterinary Education 2015; 27(1): 48-54.
  2. Perez R, Garcia M, Arias P, Gallardo M, Valenzuela S, Rudolph MI. Inhibition of xylazine induced uterine contractility by clenbuterol and nifedipine. Research in Veterinary Science. 1997; 63(1):73-76.
  3. Piccinno M, Rizzo A, Mutinati M, D'Onghia G, Sciorsci RL. Lidocaine decreases the xylazine-evoked contractility in pregnant cows. Research in Veterinary Science. 2016; 107: 267-272.
  4. Sakamoto H, Misumi K, Nakama M, AOKI Y. The effects of xylazine on intrauterine pressure, uterine blood flow, maternal and fetal cardiovascular and pulmonary function in pregnant goats. Journal of Veterinary Medical Science. 1996; 58(3): 211-217.
  5. Tsatsaris V, Cabrol D, Carbonne B. Pharmacokinetics of tocolytic agents. Clinical Pharmacokinetics. 2004; 43(13): 833-844.
  6. Jang HY, Lee KM, Park YS, Moon MJ, Hahn WB, Ahn EH. Clostridium botulinum toxin A significantly inhibits uterine contractions in rats undergoing mifepristone-induced preterm labor. Korean Journal of Obstetrics and Gynecology. 2012; 55(9): 629-635.
  7. Kido A, Togashi K, Hatayama H, Nakayama T, Yamamoto A, Kataoka M, Tulandi T. Uterine peristalsis in women with repeated IVF failures: possible therapeutic effect of hyoscine bromide. Journal of Obstetrics and Gynaecology Canada. 2009; 31(8): 732-735.
  8. Sciorsci RL, Piccinno M, Rizzo A. Scopolamine butylbromide decreases the xylazine-mediated contractility in bovine pregnant uteri. Theriogenology. 2018; 108: 348-353.
  9. Kirberger RM, Bester EG, Schulman ML, van Rensburg IJ, Hartman MJ. Ultrasonographic evaluation of fetal development in the rat. Theriogenology. 2019; 125: 24-29.
  10. Inaba T, Inoue A. Use of echography in rats for pregnancy diagnosis. Japanese Journal of Veterinary Science. 1985; 47(3): 523-525.
  11. Gomar A, Hosseini A, Mirazi N, Gomar M. Effect of Alcoholic Salvia officinale Extract on Analgesia Induced by Hyoscine in Adult Male Wistar Rats. Journal of Ardabil University of Medical Sciences. 15(3): 237-245.
  12. Enginar N, Nurten A, Türkmen AZ, Çağla B. Scopolamine-induced convulsions in fasted animals after food intake: Sensitivity of C57BL/6J mice and Sprague-Dawley rats. Epilepsy Research. 2015; 112: 150-153.
  13. Stickrod G. Ketamine/xylazine anesthesia in the pregnant rat. Journal of the American Veterinary Medical Association. 1979; 175(9): 952-953.
  14. Knight AP. Xylazine. Journal of American Veterinary Medical Association. 1980; 176: 454-455
  15. LeBlanc MM, Hubbell JA, Smith HC. The effects of xylazine hydrochloride on intrauterine pressure in the cow. Theriogenology. 1984; 21(5): 681-690.
  16. Yasuda K, Sumi G, Kanamori C, Nakajima T, Tsuzuki T, Cho H, Nishigaki A, Okada H, Kanzaki H. Effects of ovarian hormone treatment on the gene expression of muscarinic acetylcholine receptors in the ovariectomized rat myometrium. The Journal of Steroid Biochemistry and Molecular Biology. 2014; 143: 81-89.
  17. Taneike T, Kitazawa T, Funakura H, Asanuma K, Tsuji S, Yamada M, Teraoka H, Ohga A. Smooth muscle layer-specific variations in the autonomic innervation of bovine myometrium. General Pharmacology: The Vascular System. 1999; 32(1): 91-100.
  18. Kitazawa T, Hirama R, Masunaga K, Nakamura T, Asakawa K, Cao J, Teraoka H, Unno T, Komori SI, Yamada M, Wess J. Muscarinic receptor subtypes involved in carbachol-induced contraction of mouse uterine smooth muscle. Naunyn-Schmiedeberg's Archives of Pharmacology. 2008; 377(4): 503-513.
  19. Hodgson DS, Dunlop CI, Chapman PL, Smith JA. Cardiopulmonary effects of xylazine and acepromazine in pregnant cows in late gestation. American Journal of Veterinary Research. 2002; 63(12): 1695-1699.
  20. J Eesa M. The clinical evaluation of the effect of xylazine in pregnant buffaloes and cattle. Basrah Journal of Veterinary Research. 2007; 6(2): 37-41.
  21. Blanchard TL, Thompson JA, Brinsko SP, Varner DD, Love CC, Ramsey J, O'Meara A. Pregnancy rates in tranquilized maiden Thoroughbred mares. Journal of Equine Veterinary Science. 2010; 30(4): 187-190.
  22. Holden JE, Schwartz EJ, Proudfit HK. Microinjection of morphine in the A7 catecholamine cell group produces opposing effects on nociception that are mediated by α1-and α2-adrenoceptors. Neuroscience. 1999; 91(3): 979-990.
  23. Peričić D, Švob D, Jazvinšćak Jembrek M, Mirković Kos K. The involvement of α2-adrenoceptors in the anticonvulsive effect of swim stress in mice. Psychopharmacology. 2001; 158(1): 87-93.
  24. Paris A, Philipp M, Tonner PH, Steinfath M, Lohse M, Scholz J, Hein L. Activation of α2B-adrenoceptors mediates the cardiovascular effects of etomidate. The Journal of the American Society of Anesthesiologists. 2003; 99(4): 889-895.
  25. Prieto M, Gómez FM, Teresa Giralt M. Effects of acute, repeated and chronic variable stress on in vivo tyrosine hydroxylase activity and on α2-adrenoceptor sensitivity in the rat brain. Stress. 2003; 6(4): 281-287.
  26. Finn DP, Hudson AL, Kinoshita H, Coventry TL, Jessop DS, Nutt DJ, Harbuz MS. Imidazoline2 (I2) receptor-and α2-adrenoceptor-mediated modulation of hypothalamic-pituitary-adrenal axis activity in control and acute restraint stressed rats. Journal of Psychopharmacology. 2004; 18(1): 47-53.
  27. Marnet PG, Garcia-Villar R, Laurentie MP, Toutain PL. In vivo pharmacological characterization of alpha adrenergic receptors in sheep myometrium and their physiological meaning. Biology of Reproduction. 1987; 37(1): 241-248.
  28. Rodriguez-Martinez H, McKenna D, Weston PG, Gustafsson BK, Whitmore HL. Uterine motility in the cow during the estrous cycle. III. Effects of oxytocin, xylazine, and adrenoceptor blockers. Theriogenology. 1987; 27(2): 359-368.
  29. Pirnik Z, Jezova D, Mikkelsen JD, Kiss A. Xylazine activates oxytocinergic but not vasopressinergic hypothalamic neurons under normal and hyperosmotic conditions in rats. Neurochemistry International. 2005; 47(7): 458-465.
  30. Ko JC, Smith BE, Hsu WH. Xylazine enhances porcine myometrial contractility in vitro: possible involvement of α2-adrenoceptors and Ca2+ channels. Biology of Reproduction. 1990; 43(4): 614-618.
  31. Gibbs III HM, Troedsson MH. Effect of acepromazine, detomidine, and xylazine on myometrial activity in the mare. Biology of Reproduction. 1995; 52: 489-493.
  32. De Lille AJ, Silvers ML, Cadario ME, Tran TQ, Cage CL, LeBlanc MM. Interactions of xylazine and acepromazine with oxytocin and the effects of these interactions on intrauterine pressure in normal mares and mares with delayed uterine clearance. Journal of Reproduction and fertility. Supplement. 2000; (56): 373-379.
  33. Ko JC, Hsu WH, Evans LE. The effects of xylazine and alpha-adrenoreceptor antagonists on bovine uterine contractility in vitro. Theriogenology. 1990; 33(3): 601-611.
  34. Thaete LG, Levin SI, Dudley AT. Impact of anaesthetics and analgesics on fetal growth in the mouse. Laboratory Animals. 2013; 47(3): 175-183.
  35. Waldvogel D, Bleul U. Effect of xylazine, isoxsuprine, and lidocaine on Doppler sonographic uterine and umbilical blood flow measurements in cows during the last month of pregnancy. Theriogenology. 2014; 81(7): 993-1003.
  36. Toma VA, Filip A, Farcas A, Mirescu C, Rosioru C. Effect of hyoscine N-butylbromide on the skeletal muscle contraction in Wistar rat. Annals of the Romanian Society for Cell Biology. 2013; 18(2): 123.
  37. Tytgat GN. Hyoscine butylbromide. Drugs. 2007; 67(9): 1343-1357.
  38. Renner UD, Oertel R, Kirch W. Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. Therapeutic Drug Monitoring. 2005; 27(5): 655-665.
  39. Sato Y, Hotta H, Nakayama H, Suzuki H. Sympathetic and parasympathetic regulation of the uterine blood flow and contraction in the rat. Journal of the Autonomic Nervous System. 1996; 59(3): 151-158.
  40. Braun U, Gansohr B, Hässig M. Ultrasonographic evaluation of reticular motility in cows after administration of atropine, scopolamine and xylazine. Journal of Veterinary Medicine Series A. 2002; 49(6): 299-302.
  41. Rizzo A, Gazza C, Silvestre A, Maresca L, Sciorsci RL. Scopolamine for uterine involution of dairy cows. Theriogenology. 2018; 122: 35-40.
  42. Romański KW. Characteristics of phase 3-like activity and rebound excitation triggered by hexamethonium and atropine administration in the ovine small bowel. Indian Journal of Experimental Biology. 2010; 48(2): 124-132.

  • Receive Date 03 January 2023
  • Revise Date 17 January 2023
  • Accept Date 06 March 2023
  • First Publish Date 06 March 2023