Parasetamolün Sıçanlarda In Vitro Uterus Spontan Kasılmaları Üzerindeki Gevşetici Etkileri

Year 2022, Volume: 4 Issue: 2, 166 - 70, 01.05.2022

Zübeyde Ercan , Gökhan Zorlu , Özgür Bulmuş , İhsan Serhatlıoğlu , Abdullah Yaşar , Emine Kacar

https://doi.org/10.37990/medr.1027201

Abstract

Amaç: Parasetamol akut ve kronik ağrıda yaygın olarak kullanılan bir ilaçtır. Ağrı kesici ve ateş düşürücü bir ilaç olan parasetamolün gebelikte kullanımının güvenli olduğu bilinmektedir. Bu çalışmanın amacı, diöstrustaki dişi sıçanlarda parasetamolün uterus düz kas kasılma gevşeme mekanizması üzerindeki etkilerini araştırmaktır.
Materyal ve Metot: Çalışmada Wistar-albino intak dişi sıçanlar kullanıldı. Longitudinal miyometriyum şeritleri diöstrustaki hayvanlardan elde edildi. Şeritler, 1 g pasif gerilim altında krebs solüsyonu içeren izole organ banyosuna asıldı. Regülasyon periyodundan sonra, parasetamol 1000μM ve 2000μM konsantrasyonlarda kümülatif olmayan şekilde eklendi. Uygulama öncesi ve sonrası eğri altında kalan alan (AUC) ve zirveden zirveye (p-p) değerleri % değişim olarak normalize edilmiştir.
Bulgular: Parasetamol spontan uterus kontraksiyonlarının p-p ve eğri altında kalan alan parametrelerinde 1000 ve 2000 μM dozlarda istatistiksel olarak anlamlı azalmaya neden oldu (p <0.001).
Sonuçlar: Parasetamol uterus kasılmasını inhibe ederek uterus gevşemesine neden olur. Klinik kullanımında bu etki göz önünde bulundurulmalıdır.

Keywords

Parasetamol , uterus , izometrik kontraksiyon , sıçan

Relaxing Effects of Paracetamol on Uterine Spontaneous Contraction in Rats in Vitro

Abstract

Aim: Paracetamol is a commonly used drug in acute and chronic pain. It is known that paracetamol, which is a pain reliever and antipyretic drug, is safe to use during pregnancy. The aim of this study was to investigate the effects of paracetamol on the uterine smooth muscle contraction- relaxation mechanism in female rats in diestrus.
Material and Methods: Wistar-albino intact female rats were used in the study. Longitudinal strips of myometrium obtained from animals at the diestroeus stage. Stripes were suspended in an isolated organ bath containing crebs solution under 1 g passive tension. After the regulation period, paracetamol were added non-cumulatively at 1000μM and 2000μM concentrations. Before and after the application, the area under the curve (AUC) and peak to peak (p-p) values were normalized as % change.
Results: Paracetamol caused a statistically significant decrease in p-p and area under the curve parameters of spontaneous uterine contractions at 1000 and 2000 μM doses (p <0.001).
Conclusion: Paracetamol causes uterine relaxation by inhibiting uterine contraction. This effect should be taken into account in clinical use.

Keywords

Paracetamol , Uterus , Isometric Contraction , Rat

References

• 1. Roberts E, Nunes VD, Buckner S, Latchem S, Constanti M, Miller P, et al. Paracetamol: not as safe as we thought? A systematic literature review of observational studies. Annals of the rheumatic diseases. 2016;75(3):552-9.
• 2. Przybyła GW, Szychowski KA, Gmiński J. Paracetamol–An old drug with new mechanisms of action. Clinical and Experimental Pharmacology and Physiology. 2021;48(1):3-19.
• 3. Graham GG, Scott KF. Mechanism of action of paracetamol. American journal of therapeutics. 2005;12(1):46-55.
• 4. Anderson BJ. Paracetamol (Acetaminophen): mechanisms of action. Pediatric Anesthesia. 2008;18(10):915-21.
• 5. Ottani A, Leone S, Sandrini M, Ferrari A, Bertolini A. The analgesic activity of paracetamol is prevented by the blockade of cannabinoid CB1 receptors. European journal of pharmacology. 2006;531(1-3):280-1.
• 6. Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P, et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2003;62(12):1145-55.
• 7. Saragiotto BT, Machado GC, Ferreira ML, Pinheiro MB, Shaheed CA, Maher CG. Paracetamol for low back pain. Cochrane Database of Systematic Reviews. 2016(6).
• 8. Towheed T, Maxwell L, Judd M, Catton M, Hochberg MC, Wells GA. Acetaminophen for osteoarthritis. Cochrane Database of Systematic Reviews. 2006(1).
• 9. Zhang W, Nuki G, Moskowitz R, Abramson S, Altman R, Arden N, et al. OARSI recommendations for the management of hip and knee osteoarthritis: part III: Changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis and cartilage. 2010;18(4):476-99.
• 10. Zhang W, Jones A, Doherty M. Does paracetamol (acetaminophen) reduce the pain of osteoarthritis?: a meta-analysis of randomised controlled trials. Annals of the rheumatic diseases. 2004;63(8):901-7.
• 11. Burdan F, Starosławska E, Szumiło J. Prenatal tolerability of acetaminophen and other over-the-counter non-selective cyclooxygenase inhibitors. Pharmacological Reports. 2012;64(3):521-7.
• 12. Collins E. Maternal and fetal effects of acetaminophen and salicylates in pregnancy. Obstetrics and gynecology. 1981;58(5 Suppl):57S-62S.
• 13. Stergiakouli E, Thapar A, Davey Smith G. Association of Acetaminophen Use During Pregnancy With Behavioral Problems in Childhood: Evidence Against Confounding. JAMA pediatrics. 2016;170(10):964-70.
• 14. Thiele K, Solano ME, Huber S, Flavell RA, Kessler T, Barikbin R, et al. Prenatal acetaminophen affects maternal immune and endocrine adaptation to pregnancy, induces placental damage, and impairs fetal development in mice. The American journal of pathology. 2015;185(10):2805-18.
• 15. Rayburn W, Shukla U, Stetson P, Piehl E. Acetaminophen pharmacokinetics: comparison between pregnant and nonpregnant women. American journal of obstetrics and gynecology. 1986;155(6):1353-6.
• 16. O'Brien WF, Krammer J, O'Leary TD, Mastrogiannis DS. The effect of acetaminophen on prostacyclin production in pregnant women. American journal of obstetrics and gynecology. 1993;168(4):1164-9.
• 17. Aleixo JF, Pereira MRF, Montagnini BG, Pereira MJD, Forcato S, Moreira EG, et al. Effect of paracetamol treatment on maternal care and reproductive outcomes in female rat offspring. Reproduction, fertility, and development. 2020;32(18):1311-25.
• 18. Rebordosa C, Kogevinas M, Horváth-Puhó E, Nørgård B, Morales M, Czeizel AE, et al. Acetaminophen use during pregnancy: effects on risk for congenital abnormalities. American journal of obstetrics and gynecology. 2008;198(2):178. e1-. e7.
• 19. Rebordosa C, Kogevinas M, Bech BH, Sørensen HT, Olsen J. Use of acetaminophen during pregnancy and risk of adverse pregnancy outcomes. International journal of epidemiology. 2009;38(3):706-14.
• 20. Koehn L, Habgood M, Huang Y, Dziegielewska K, Saunders N. Determinants of drug entry into the developing brain. F1000Research. 2019;8.
• 21. Fisher BG, Thankamony A, Hughes IA, Ong KK, Dunger DB, Acerini CL. Prenatal paracetamol exposure is associated with shorter anogenital distance in male infants. Human reproduction (Oxford, England). 2016;31(11):2642-50.
• 22. Czeizel AE, Dudás I, Puhó E. Short‐term paracetamol therapy during pregnancy and a lower rate of preterm birth. Paediatric and perinatal epidemiology. 2005;19(2):106-11.
• 23. Beroyz G, Casale R, Farreiros A, Palermo M, Margulies M, Voto L, et al. CLASP-A randomized trial of low-dose aspirin for the prevention and treatment of preeclampsia among 9364 pregnant-women. Lancet. 1994;343(8898).
• 24. Thulstrup AM, Sørensen HT, Nielsen GL, Andersen L, Barrett D, Vilstrup H, et al. Fetal growth and adverse birth outcomes in women receiving prescriptions for acetaminophen during pregnancy. American journal of perinatology. 1999;16(07):321-6.
• 25. McCormick MC. The contribution of low birth weight to infant mortality and childhood morbidity. New England journal of medicine. 1985;312(2):82-90.
• 26. Hack M, Fanaroff AA. Outcomes of extremely immature infants--a perinatal dilemma. Mass Medical Soc; 1993.
• 27. Tucker JM, Goldenberg RL, Davis RO, Copper RL, Winkler CL, Hauth JC. Etiologies of preterm birth in an indigent population: is prevention a logical expectation? Obstetrics and gynecology. 1991;77(3):343-7.
• 28. Pastore LM, Hertz-Picciotto I, Beaumont JJ. Risk of stillbirth from medications, illnesses and medical procedures. Paediatric and perinatal epidemiology. 1999;13(4):421-30.
• 29. Li D-K, Liu L, Odouli R. Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study. Bmj. 2003;327(7411):368.
• 30. Yalcin N, Uzun ST, Reisli R, Borazan H, Otelcioglu S. A comparison of ketamine and paracetamol for preventing remifentanil induced hyperalgesia in patients undergoing total abdominal hysterectomy. International journal of medical sciences. 2012;9(5):327.
• 31. Arici S, Gurbet A, Türker G, Yavaşcaoğlu B, Sahin S. Preemptive analgesic effects of intravenous paracetamol in total abdominal hysterectomy. Agri : Agri (Algoloji) Dernegi'nin Yayin organidir = The journal of the Turkish Society of Algology. 2009;21(2):54-61.
• 32. Açmaz G, Aksoy H, Özoğlu N, Aksoy Ü, Albayrak E. Effect of paracetamol, dexketoprofen trometamol, lidocaine spray, and paracervical block application for pain relief during suction termination of first-trimester pregnancy. BioMed research international. 2013;2013:869275.