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The Effect of Paracetamol on The Development of Chicken Embryos
Abstract
Paracetamol (N-Acetylaminophenol) is the most widely used over-the-counter drug in the world. Although considered safe for pregnant mothers, there is a concern regarding the teratogenic effect of paracetamol. This study aims to observe the teratogenic effect of paracetamol developing embryos. Using chicken embryos, the embryos were incubated for 48 hours and then injected with paracetamol in 3 concentrations, namely 10 ppm, 15 ppm, and 20 ppm. The control group and treatment group consisted of 3 replicates of fertile embryos. Then, the embryos were incubated again for 48 hours in the incubator. Data analysis was carried out qualitatively by observing any developmental alterations. Results showed that paracetamol caused enlargement of the head and heart edema. Exposure to paracetamol at concentrations of 15 ppm and 20 ppm affects the morphology of chicken embryos, especially the formation of the head and disrupts the process of angiogenesis and normal heart formation, causing bleeding and edema at higher concentrations.
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Abassi, Z., Khoury, E. E., Karram, T., & Aronson, D. (2022). Edema formation in congestive heart failure and the underlying mechanisms. In Frontiers in Cardiovascular Medicine (Vol. 9). Frontiers Media S.A. doi:https://doi.org/10.3389/fcvm.2022.933215
Aldridge, D. R., Tranah, E. J., & Shawcross, D. L. (2015). Pathogenesis of hepatic encephalopathy: Role of ammonia and systemic inflammation. Journal of Clinical and Experimental Hepatology, 5. doi:https://doi.org/10.1016/j.jceh.2014.06.004
Alhouayek, M., & Muccioli, G. G. (2014). COX-2-derived endocannabinoid metabolites as novel inflammatory mediators. Trends in pharmacological sciences, 35(6), 284-292. doi:http://dx.doi.org/10.1016/j.tips.2014.03.001
Alwan, S., Conover, E. A., Harris-Sagaribay, L., Lamm, S. H., Lavigne, S. V., Lusskin, S. I., Obican, S. G., Romeo, A. N., Scialli, A. R., & Wisner, K. L. (2022). Paracetamol use in pregnancy—Caution over causal inference from available data. Nature Reviews Endocrinology, 18(3), 190–190. doi:https://doi.org/10.1038/s41574-021-00606-x
Andrade, C. (2016). Use of Acetaminophen (Paracetamol) During Pregnancy and the Risk of Attention-Deficit/Hyperactivity Disorder in the Offspring: (Clinical and Practical Psychopharmacology). The Journal of Clinical Psychiatry, 77(03), e312–e314. doi:https://doi.org/10.4088/JCP.16f10721
Athersuch, T. J., Antoine, D. J., Boobis, A. R., Coen, M., Daly, A. K., Possamai, L., Nicholson, J. K., & Wilson, I. D. (2018). Paracetamol metabolism, hepatotoxicity, biomarkers and therapeutic interventions: A perspective. Toxicology Research, 7(3), 347–357. doi:https://doi.org/10.1039/c7tx00340d
Bauer, A. Z., Kriebel, D., Herbert, M. R., Bornehag, C.-G., & Swan, S. H. (2018). Prenatal paracetamol exposure and child neurodevelopment: A review. Hormones and Behavior, 101, 125–147. doi:https://doi.org/10.1016/j.yhbeh.2018.01.003
Bauer, A. Z., Swan, S. H., Kriebel, D., Liew, Z., Taylor, H. S., Bornehag, C.-G., Andrade, A. M., Olsen, J., Jensen, R. H., Mitchell, R. T., Skakkebaek, N. E., Jégou, B., & Kristensen, D. M. (2021). Paracetamol use during pregnancy—A call for precautionary action. Nature Reviews Endocrinology, 17(12), 757–766. doi: https://doi.org/10.1038/s41574-021-00553-7
Becker, W. J. (2015). Acute Migraine Treatment in Adults. Headache: The Journal of Head and Face Pain, 55(6), 778–793. doi:https://doi.org/10.1111/head.12550
Cha, Y.I., Solnica-Krezel, L., DuBois, R.N., (2006). Fishing for prostanoids: Deciphering the developmental functions of cyclooxygenase-derived prostaglandins. Developmental Biology 289, 263–272. doi:https://doi.org/10.1016/j.ydbio.2005.10.013
Chung, W., & Lin, C. (2018). Increased risk of congestive heart failure in patients with acetaminophen poisoning: A nationwide cohort study. Journal of Applied Toxicology, 38(5), 766–772. doi:https://doi.org/10.1002/jat.3586
Damkier, P., Cleary, B., Weber-Schoendorfer, C., Shechtman, S., Cassina, M., Panchaud, A., & Diav-Cirtin, O. (2022). Handle with care—Interpretation, synthesis, and dissemination of data on paracetamol in pregnancy. Nature Reviews Endocrinology, 18(3), 191–191. doi:https://doi.org/10.1038/s41574-021-00605-y
Duggan, K. C., Hermanson, D. J., Musee, J., Prusakiewicz, J. J., Scheib, J. L., Carter, B. D., ... & Marnett, L. J. (2011). (R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2. Nature Chemical Biology, 7(11), 803-809. doi:https://doi.org/10.1038/nchembio.663
European Medicines Agency. (2019). PRAC recommendations on safety signals | European Medicines Agency. https://www.ema.europa.eu/en/human-regulatory-overview/post-authorisation/pharmacovigilance-post-authorisation/signal-management/prac-recommendations-safety-signals
Food and Drug Administration, C. for D. E. and. (2019). FDA Drug Safety Communication: The FDA has reviewed possible risks of pain medicine use during pregnancy. FDA. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-has-reviewed-possible-risks-pain-medicine-use-during-pregnancy
Graham, G. G., & Scott, K. F. (2003). Mechanisms of action of paracetamol and related analgesics. Inflammopharmacology, 11, 401-413. doi:https://doi.org/10.1163/156856003322699573
Graham, G. G., Davies, M. J., Day, R. O., Mohamudally, A., & Scott, K. F. (2013). The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity, and recent pharmacological findings. Inflammopharmacology, 21, 201-232. doi:https://doi.org/10.1007/s10787-013-0172-x
Gutiérrez-Noya, V.M., Gómez-Oliván, L.M., Ramírez-Montero, M.D.C., Islas-Flores, H., Galar-Martínez, M., García-Medina, S., 2021. Survival and malformations rates, oxidative status in early life stages of Cyprinus carpio due to exposure to environmentally realistic concentrations of paracetamol. Science of The Total Environment 768, 144585. doi:https://doi.org/10.1016/j.scitotenv.2020.144585
Lee, Y. S., Kim, H., Brahim, J. S., Rowan, J., Lee, G., & Dionne, R. A. (2007). Acetaminophen selectively suppresses peripheral prostaglandin E2 release and increases COX-2 gene expression in a clinical model of acute inflammation. Pain, 129(3), 279-286. doi:https://doi.org/10.1016/j.pain.2006.10.020
Lupattelli, A., Spigset, O., Twigg, M. J., Zagorodnikova, K., Mårdby, A. C., Moretti, M. E., Drozd, M., Panchaud, A., Hämeen-Anttila, K., Rieutord, A., Gjergja Juraski, R., Odalovic, M., Kennedy, D., Rudolf, G., Juch, H., Passier, A., Björnsdóttir, I., & Nordeng, H. (2014). Medication use in pregnancy: A cross-sectional, multinational web-based study. BMJ Open, 4(2), e004365. doi:https://doi.org/10.1136/bmjopen-2013-004365
Mazaleuskaya LL, Sangkuhl K, Thorn CF, FitzGerald GA, Altman RB, & Klein TE. (2015). Pharm GKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics, 25: 416–26.
McCrae, J. C., Morrison, E. E., MacIntyre, I. M., Dear, J. W., & Webb, D. J. (2018). Long?term adverse effects of paracetamol–a review. British journal of clinical pharmacology, 84(10), 2218-2230. doi:https://doi.org/10.1111/bcp.13656
Moore, R. A., & Moore, N. (2016). Paracetamol and pain: The kiloton problem. European Journal of Hospital Pharmacy, 23(4), 187–188. doi:https://doi.org/10.1136/ejhpharm-2016-000952
Moungmaithong, S., Leung, B. W., Sahota, D. S., Wang, C. C., Leung, T. Y., & Poon, L. C. (2022). Assessment of embryo morphology following perinatal exposure to aspirin, ibuprofen, and paracetamol using whole embryo culture system. The Journal of Maternal-Fetal & Neonatal Medicine, 35(25), 8786–8793. doi:https://doi.org/10.1080/14767058.2021.2005020
Nilsen, K., Staff, A. C., & Krogsrud, S. K. (2023). Paracetamol use in pregnancy: Not as safe as we may think? Acta Obstetricia et Gynecologica Scandinavica, 102(6), 652–656. doi:https://doi.org/10.1111/aogs.14557
Ohlsson, A., & Shah, P. S. (2020). Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database of Systematic Reviews, 2020(1). doi:https://doi.org/10.1002/14651858.CD010061.pub4
Pawlikowski, B., Vogler, T. O., Gadek, K., & Olwin, B. B. (2017). Regulation of skeletal muscle stem cells by fibroblast growth factors. Developmental Dynamics, 246(5), 359-367. doi:https://doi.org/10.1002/dvdy.24495
Pini, L. A., Del Bene, E., Zanchin, G., Sarchielli, P., Di Trapani, G., Prudenzano, M. P., LaPegna, G., Savi, L., Di Loreto, G., Dionisio, P., & Granella, F. (2008). Tolerability and efficacy of a combination of paracetamol and caffeine in the treatment of tension-type headache: A randomized, double-blind, double-dummy, cross-over study versus placebo and naproxen sodium. The Journal of Headache and Pain, 9(6), 367–373. doi:https://doi.org/10.1007/s10194-008-0071-5
Radi, Z. A., Meyerholz, D. K., & Ackermann, M. R. (2010). Pulmonary cyclooxygenase-1 (COX-1) and COX-2 cellular expression and distribution after respiratory syncytial virus and parainfluenza virus infection. Viral immunology, 23(1), 43-48. doi:https://doi.org/10.1089/vim.2009.004
Rayburn, W., Shukla, U., Stetson, P., & Piehl, E. (1986). Acetaminophen pharmacokinetics: Comparison between pregnant and nonpregnant women. American Journal of Obstetrics and Gynecology, 155(6), 1353–1356. doi: https://doi.org/10.1016/0002-9378(86)90173-0
Ribatti, D., & Annese, T. (2023). Chick embryo in experimental embryology and more. Pathology - Research and Practice, 245, 154478. doi:https://doi.org/10.1016/j.prp.2023.154478
Rosas-Ramírez, J.R., Orozco-Hernández, J.M., Elizalde-Velázquez, G.A., Raldúa, D., Islas-Flores, H., Gómez-Oliván, L.M., (2022). Teratogenic effects induced by paracetamol, ciprofloxacin, and their mixture on Danio rerio embryos: Oxidative stress implications. Science of The Total Environment 806, 150541. doi:https://doi.org/10.1016/j.scitotenv.2021.150541
Roy, P., Das, S., Auddy, R. G., Saha, A., & Mukherjee, A. (2013). Engineered andrographolide nanoparticles mitigate paracetamol hepatotoxicity in mice. Pharmaceutical Research, 30(5), 1252–1262. doi:https://doi.org/10.1007/s11095-012-0964-5
Schieber, M., & Chandel, N. S. (2014). ROS function in redox signaling and oxidative stress. Current biology, 24(10), R453-R462. ROS Function in Redox Signaling and Oxidative Stress - ScienceDirect
Scott, T. R., Kronsten, V. T., Hughes, R. D., & Shawcross, D. L. (2013). Pathophysiology of cerebral oedema in Acute liver failure. World Journal of Gastroenterology, 19(48), 9240. doi:https://doi.org/10.3748/wjg.v19.i48.9240
Sekhar, R. V., Patel, S. G., Guthikonda, A. P., Reid, M., Balasubramanyam, A., Taffet, G. E., & Jahoor, F. (2011). Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. The American Journal of Clinical Nutrition, 94(3), 847–853. doi:https://doi.org/10.3945/ajcn.110.003483
Seo, M. J., & Oh, D. K. (2017). Prostaglandin synthases: Molecular characterization and involvement in prostaglandin biosynthesis. Progress in lipid research, 66, 50-68. doi:http://dx.doi.org/10.1016/j.plipres.2017.04.003
Sepehrinezhad, A., Zarifkar, A., Namvar, G., Shahbazi, A., & Williams, R. (2020). Astrocyte swelling in hepatic encephalopathy: molecular perspective of cytotoxic edema. Metabolic Brain Disease 2020 35:4, 35(4), 559–578. doi:https://doi.org/10.1007/S11011-020-00549-8
Sharma, C. V., & Mehta, V. (2014). Paracetamol: Mechanisms and updates. Continuing Education in Anaesthesia Critical Care & Pain, 14(4), 153–158. doi:https://doi.org/10.1093/bjaceaccp/mkt049
Walker, V., Mills, G. A., Anderson, M. E., Ingle, B. L., Jackson, J. M., Moss, C. L., Sharrod-Cole, H., & Skipp, P. J. (2016). The acetaminophen metabolite N-acetyl-P-benzoquinone imine (NAPQI) inhibits glutathione synthetasein vitro; a clue to the mechanism of 5-oxoprolinuric acidosis? Xenobiotica, 47(2), 164–175. doi:https://doi.org/10.3109/00498254.2016.1166533
Waller, J. P., Howell, J. A., Peterson, H., George, E. M., & Bidwell III, G. L. (2021). Elastin-like polypeptide: VEGF-B fusion protein for treatment of preeclampsia. Hypertension, 78(6), 1888-1901. doi:https://doi.org/10.1161/HYPERTENSIONAHA.121.17713
Werler, M. M., Mitchell, A. A., Hernandez-Diaz, S., Honein, M. A., & the National Birth Defects Prevention Study. (2005). Use of over-the-counter medications during pregnancy. American Journal of Obstetrics and Gynecology, 193(3), 771–777. doi:https://doi.org/10.1016/j.ajog.2005.02.100
Xia, L., Zheng, L., & Zhou, J. L. (2017). Effects of ibuprofen, diclofenac, and paracetamol on hatch and motor behavior in developing zebrafish ( Danio rerio ). Chemosphere, 182, 416–425. doi:https://doi.org/10.1016/j.chemosphere.2017.05.054
Yang, C., Li, P., Ding, X., Sui, H. C., Rao, S., Hsu, C. H., Leung, W. P., Cheng, G. J., Wang, P., & Zhu, B. T. (2020). Mechanism for the reactivation of the peroxidase activity of human cyclooxygenases: investigation using phenol as a reducing cosubstrate. Scientific Reports, 10(1), 15187. doi:https://doi.org/10.1038/s41598-020-71237-x
DOI: https://doi.org/10.14421/biomedich.2024.132.559-564
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