Sıçan Fetusların Karaciğerlerinde Parasetamolün Vascular Endothelial Growth Factor, Sclerostin ve FETUIN-A Üzerine Etkileri
Abstract
Amaç: Parasetamol gebe, çocuk ve yaşlılar gibi önemli gruplar tarafından yaygın olarak kullanılmaktadır. Özellikle gebelikte fazla dozda alınan parasetamol karaciğer yetmezliklerine neden olmaktadır. Çalışmamızın amacı gebelik döneminde yaygın olarak olarak kullanılan parasetamolün fetüs karaciğeri üzerine etkilerini biyokimyasal olarak araştırmaktır.
Yöntemler: Çalışmamızda 10 adet (n=2) gebe sıçanlardan Wistar Albino cinsi rastgele seçilen kontrol grubu, 50 mg/kg parasetamol grubu, 125 mg/kg parasetamol grubu, 250 mg/kg parasetamol grubu ve 500 mg/kg parasetamol grubu olmak üzere beş gruba ayrıldı. Gavaj yoluyla parasetamol, belirlenen dozlarda gebe sıçanlara verildi. Gebeliğin 20. gününde sezeryan ile fetüsler alındı (her gruptan 10 adet fetus alındı). Sonrasında fetus karaciğerleri biyokimysasal analiz için alındı. Biyokimyasal olarak vascular endothelial growth factor A (VEGF-A), FETU-A (α2-heremans-schmid glikoprotein) ve Sclerostin (SOST) değerleri incelendi.
Bulgular: Bu çalışmada parasetamol dozu arttıkça karaciğer hepatosit hücrelerinde değişiklikler görülmektedir. VEGF-A ve FETU-A’da düzenli artış görülmektedir. SOST ise 250 mg/kg dozunda yükselirken, 500 mg/kg parasetamol grubunda azalmıştır. (p<0.05)
Sonuç: Sonuç olarak gebelikte yüksek dozda parasetamol kullanımının fetüskaraciğerinde ve biyokimyasal değerde değişiklik meydana getirdiği görülmektedir. Bu çalışmada gebelikte masum analjezik olarak reçetesiz satılan ve çok kullanılan parasetamol’un yüksek dozda kullanımı konusunda dikkat edilmesi gerektiğini ve bu çalışmanın yapılacak diğer çalışmalara referans olacağını düşünmekteyiz.
Keywords
References
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- 2. Kathryn AM, Elizabeth EH, Amelia KW, Kenneth JR, Ellen MM, Lauren AW. Preconception use of pain-relievers and time-to-pregnancy: a prospective cohort study. Human Reproduction. 2017;32:103–111. DOI:10.1093/humrep/dew272.
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Effects of Paracetamol on Vascular Endothelial Growth Factor, Sclerostin and FETUIN-A in the Liver of Rat Fetuses
Abstract
Aim: Paracetamol is widely used by important societal groups such as pregnant women and the elderly. Paracetamol, taken in high doses especially during pregnancy, causes liver failure. The aim of our study is to investigate the effects of paracetamol, which is widely used during pregnancy, on the fetal liver.
Methods: In our study, five groups of randomly selected rats from 10 Wistar Albino rats (n=2) were formed as control group, 50 mg / kg paracetamol group, 125 mg / kg paracetamol group, 250 mg / kg paracetamol group and 500 mg / kg paracetamol group. Paracetamol by gavage was given to pregnant rats in specified doses. Fetuses were taken by cesarean on the 20th day of pregnancy (10 fetuses were taken from each group). The fetus livers were then taken for biochemical analysis. Biochemically, vascular endothelial growth factor A (VEGF-A), FETU-A (FETUIN-A) (α2-heremans-schmid glikoprotein) and Sclerostin (SOST) values were examined.
Results: In this study, changes in liver hepatocyte cells are seen as the dose of paracetamol increases. Regular increase is observed in VEGF-A and FETU-A. SOST increased at a dose of 250 mg / kg and decreased in the group of 500 mg / kg paracetamol. (p<0.05).
Conclusions: As a result, it is seen that the use of high doses of paracetamol in pregnancy causes changes in the liver and many biochemical values on the fetus. We think that an overdosing of paracetamol, which is sold without prescription and used as an innocent analgesic during pregnancy, should be examined and this study will be a reference for other studies to be conducted.
Keywords
References
- 1. Dharmage SC, Allen KJ. Does regular paracetamol ingestion increase the risk of developing asthma. Clin. Exp. Allergy. 2011;41:459-460. DOI: 10.1111/j.1365-2222.2011.03716.x
- 2. Kathryn AM, Elizabeth EH, Amelia KW, Kenneth JR, Ellen MM, Lauren AW. Preconception use of pain-relievers and time-to-pregnancy: a prospective cohort study. Human Reproduction. 2017;32:103–111. DOI:10.1093/humrep/dew272.
- 3. Tandoğan M, Emektar E, Dağar S, Yüzbaşıoğlu Y, Karaatlı RH, Çevik Y. Acil Servise Parasetamol İntoksikasyonu Nedeniyle Başvuran Hastaların Değerlendirilmesi. Eurasian J Tox. 2019;1(1):11-14.
- 4. Avella-Garcia CB, Julvez J, Fortuny J, Rebordosa C, Garcia ER, et al. Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms. Int J Epidemiol 2016;45:1987–96. DOI: 10.1093/ije/dyw115.
- 5. Wilkes JM, Clark LE, Herrera JL. Acetaminophen Overdose in Pregnancy. Southern Medical Journal. 2005;(98):1118-1122. DOI: 10.1097/01.smj.0000184792.15407.51
- 6. Arana A, Morton NS, Hansen TG. Treatment with paracetamol in infants. Acta Anaesthesiologica Scandinavica, 2001;45:20-29. DOI: 10,1034 / j.1399-6576.2001.450104.x
- 7. Scialli, A. R., Ang, R., Breitmeyer, J., & Royal, M. A. (2010). A review of the literature on the effects of acetaminophen on pregnancy outcome. Reproductive Toxicology, 30: 495-507. DOI: 10.1016/j.reprotox.2010.07.007.
- 8. Hendrickson RG, Bizovi KE. Acetaminophene. In Flomenbaum NE, Goldfrank LR, Hoffman RS, Howland MA, Lewin NA, et al Editors. Goldfrank’s Toxicologic Emergencies. 8th ed. New York: McGraw-Hill; 2006. p.333-43.
- 9. Kim WY, Lee HY. Brain angiogenesis in developmental and pathological processes: mechanism and therapeutic intervention in brain tumors. FEBS Journal 2009; 276:4653±64. DOI: 10.1111/j.1742-4658.2009.07177.x PMID: 19664069
- 10. Mohsen Azimi-Nezhad. Vascular endothelial growth factor from embryonic status to cardiovascular pathology. Reports of Biochemistry & Molecular Biology. 2014;2:59-69. PMID: 26989723.
- 11. Lebreton JP, Joisel F, Raoult JP, Lannuzel B, Rogez JP, Humbert G. Serum concentration of human alpha 2 HS glycoprotein during the inflammatory process: evidence that alpha 2 HS glycoprotein is a negative acute-phase reactant. J Clin Invest 1979;64:1118-29. DOI:10.1172 / JCI109551
- 12. Blinova EV, Halzova MA, Blinov DS. A Protectıve Role For Magnesıum 2-Amınoethansulfonate In Paracetamol And Ethanol-Induced Lıver Injury In Pregnant Rats. Eksperimental’naia I Klinicheskaia Gastroenterologiia. 2016;50-53. PMID: 29889373
- 13. Zou. Zou Y, Yang M, Wang J, Cui L, Jiiang Z, Ding J, Li M, Zhou H. ‘’ Association of sclerostin with cardiovascular events and mortality in dialysis patients.’’ Ren Fail. 2020;42(1):282-288. DOI: 10.1080/0886022X.2020.1741386.
- 14. Lubawy WC, Garrett RJ. Effects of aspirin and acetaminophen on fetal and placental growth in rats. J Pharm Sci 1977; 66: 111-113, Neto JA, Oliveira-Filho RM, Simões MJ, Soares JM, et al. Long-term acetaminophen (paracetamol) treatment causes liver and kidney ultra-structural changes during rat pregnancy. Clin Exp Obstet Gynecol 2004;31:221-224.
- 15. Abdeen A, Andelkader A, Abdo M, Wareth G, Aboubakr M, Aleya L, et al. Protective effect of cinnamon against acetaminophen-mediated cellular damage and apoptosis in renal tissue. Environmental science and pollution research international. 2019;26:240–264. DOI: 10.1007 / s11356-018-3553-2
- 16. Karakuş O, İlkaya F, Yılmaz MZ. Parasetamol ve siklooksijenaz enzim inhibisyonu. J Exp Clin Med 2013;30(1):9-14. DOI: 10.5835/jecm.omu.30.s1.002
- 17. Koehn L, Habgood M, Huang Y, Dziegielewska K, Saunders N. Determinants of drug entry into the developing brain. F1000Research 2019;8:1372. DOI: 10.12688/f1000research.20078.1
- 18. Brown JM, A mechanistic study of S-Adenosyl-L-methionine protection against acetaminophen hepatotoxicity, Crop Sci. 2012;52:1469. DOI: 10.1016 / j.toxlet.2012.05.018
- 19. Schilling A, Corey R, Leonard M, Eghtesad B. Acetaminophen: old drug, new warnings, Cleve. Clin. J. Med. 2010;77:19–27. DOI: 10.3949 / ccjm.77a.09084.
- 20. Holm JB, Chalmey C, Modick H, Jensen LS, Dierkes G, Weiss T, et al. Aniline Is Rapidly Converted Into Paracetamol Impairing Male Reproductive Development. Toxicol Sci. 2015;148(1):288-298. DOI: 10.1093 / toxsci / kfv179.
- 21. Momma K, Takao A. Transplacental cardiovascular effects of four popular analgesics in rats. Am J Obstet Gynecol 1990;162(5):1304-1310. DOI:10,1016 / 0002-9378 (90) 90042-6
- 22. D. Wu, A.I. Cederbaum, Inhibition of autophagy promotes CYP2E1-dependent toxicity in HepG2 cells via elevated oxidative stress, mitochondria dysfunction and activation of p38 and JNK MAPK, Redox Bio. 2013;1:552–565. DOI: 10.1016 / j.redox.2013.10.008
- 23. Carvalho NR, Rosa EFD, Silva MH, Tassi CC, Dalla Corte CL, Carbajo-Pescador S, et al. New therapeutic approach: Diphenyl diselenide reduces mitochondrial dysfunction in acetaminophen-induced acute liver failure, PLoS One. 2013;8(12):e81961. DOI: 10.1371/journal.pone.0081961.
- 24. Stark KL, Harris C, Juchau MR. Modulation of the embryotoxicity and cytotoxicity elicited by 7-hydroxy-2-acetylaminofluorene and acetaminophen via deacetylation. Toxicol Appl Pharmacol 1989;97(3):548-560.
- 25. Chen C, Liu X, Qi S, Dias ACP, Yan J, Zhang X. Hepatoprotective effect of Phellinus linteus mycelia polysaccharide (PL-N1) against acetaminophen-induced liver injury in mouse, International Journal of Biological Macromolecules 2019. pii: S0141-8130(19)34796-8. DOI: 10.1016/j.ijbiomac.2019.11.002.
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Research Article |
| Authors | |
| Publication Date | July 12, 2020 |
| Submission Date | February 12, 2020 |
| Acceptance Date | April 15, 2020 |
| Published in Issue | Year 2020 Volume: 4 Issue: 2 |
This Journal is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.