WHAT IS THE EFFECTS OF PARACETAMOL APPLIED AT DIFFERENT DOSES TO HEAVY METAL LEVELS IN RAT FETUS?
Keywords:
Paracetamol, Placenta, Fetus, Pb, Co, Chelator
Abstract
Paracetamol is the first preferred pharmacological agent as a pain reliever and antipyretic in all periods of pregnancy. In this study, we aimed to analyze trace element and heavy metal levels in the placenta, intestinal and kidney tissues of rats in the early development period of paracetamol. Sixteen pregnant rats were randomly divided into four groups; the control group, the 50 mg/kg paracetamol group, the 250 mg/kg paracetamol group, the 500 mg/kg paracetamol group. There was a statistically significant decrease in the placental weight of the experimental groups compared to the control group. However, a statistically significant difference was found in terms of cobalt (Co) and lead (Pb) levels compared to the control group and the groups that received various doses of paracetamol. There were also statistically significant differences in intestinal chromium (Cr), selenium (Se) and cadmium (Cd) levels in the studied groups. In addition, significant differences were detected in all trace elements and heavy metal levels except Cd in the groups studied in kidney tissue (p <0.01 for all).
As a result, it was determined that the use of paracetamol during pregnancy disrupted the current balance due to the increase in dose. In addition, it was observed that the weight of the placenta decreased due to the paracetamol dose, and the placenta Pb and Co levels increased. In other tissues, there was no toxic concentration at heavy metal and trace element levels, but the highest levels were determined in the control group.
References
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Allergy, 41(4), 459-460. DOI:
https://doi.org/10.1111/j.1365-2222.2011.03716.x
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Parasetamol ve siklooksijenaz enzim inhibisyonu. Journal of Experimental and Clinical
Medicine, 30(1s), 9-14. DOI:
10.5835/jecm.omu.30.s1.002 Kaya S, Pirinçci İ, Bilgili A. (2002). Veteriner Hekimliğinde Toksikoli, 2nd edition,pp. 191-230. Medisan Publishing House, Ankara, TURKEY.
Lauwerys, R., & Lison, D. (1994). Health risks associated with cobalt exposure—an overview. Science of the Total Environment, 150(1-3), 1-6. DOI:
https://doi.org/10.1016/0048-9697(94)90125-2
Lawton, L. J., & Donaldson, W. E. (1991). Leadinduced tissue fatty acid alterations and lipid peroxidation. Biological trace element research, 28(2),
83. DOI: https://doi.org/10.1007/BF02863075
Lim, S. Y., Doherty, J. D., McBride, K., MillerIhli, N. J., Carmona, G. N., Stark, K. D., & Salem Jr, N. (2005). Lead exposure and (n-3) fatty acid deficiency during rat neonatal development affect subsequent spatial task performance and olfactory
discrimination. The Journal of nutrition, 135(5), 1019-
1026. DOI: https://doi.org/10.1093/jn/135.5.1019
Lubawy, W. C., & Garrett, R. B. (1977). Effects of aspirin and acetaminophen on fetal and placental growth in rats. Journal of pharmaceutical sciences, 66(1), 111-113. DOI:
https://doi.org/10.1002/jps.2600660129
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Prescott L.F. (1996). Paracetamol (acetaminophen), 2nd edition. Taylor & Francis Ltd., London, UK.
Price, V. F., Miller, M. G., & Jollow, D. J. (1987). Mechanisms of fasting-induced potentiation of acetaminophen hepatotoxicity in the rat. Biochemical pharmacology, 36(4), 427-433. DOI:
https://doi.org/10.1016/0006-2952(87)90346-7
Rebordosa, C., Kogevinas, M., Bech, B. H., Sørensen, H. T., & Olsen, J. (2009). Use of acetaminophen during pregnancy and risk of adverse pregnancy outcomes. International journal of epidemiology, 38(3), 706-714. DOI:
https://doi.org/10.1093/ije/dyp151
Reel, J. R., Lawton, A. D., & LAMB IV, J. C. (1992). Reproductive toxicity evaluation of acetaminophen in Swiss CD-1 mice using a continuous breeding protocol. Toxicological Sciences, 18(2), 233-
239. DOI: https://doi.org/10.1093/toxsci/18.2.233
Robson, S. (2011). Pain relief in pregnancy. O&G Magazine, 13(1).
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(4), 495-507. DOI: https://doi.org/10.1016/j.reprotox.2010.07.007
Slattery, J. T., & Levy, G. (1979). Pharmacokinetic model of acetaminophen elimination. American journal of hospital pharmacy, 36(4), 440-444. DOI:
https://doi.org/10.1093/ajhp/36.4.440
Swierkosz, T. A., Jordan, L., McBride, M., McGough, K., Devlin, J., & Botting, R. M. (2002). Actions of paracetamol on cyclooxygenases in tissue and cell homogenates of mouse and rabbit. Medical Science Monitor, 8(12), BR496-BR503.
Şavlı, E. (2012). Paracetamol use in pregnancy,
Review. J Exp Clin Med; 29: 91-94. DOI:
10.5835/jecm.omu.29.02.002
Ulger H., & Pratten M. K. (1996). The effect of VEGF on embryonic development and yolk sac vascularisation. J Anat; 189(1): 239-243.
Vestergaard, P., Hermann, P., Jensen, J. E., Eiken, P., & Mosekilde, L. (2012). Effects of paracetamol, non-steroidal anti-inflammatory drugs, acetylsalicylic acid, and opioids on bone mineral density and risk of fracture: results of the Danish Osteoporosis Prevention
Study (DOPS). Osteoporosis International, 23(4), 1255-1265. DOI: https://doi.org/10.1007/s00198-0111692-0
Viberg, H., Eriksson, P., Gordh, T., & Fredriksson, A. (2014). Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters its analgesic and anxiolytic response in adult male mice. toxicological sciences, 138(1), 139-147. DOI:
https://doi.org/10.1093/toxsci/kft329
Von Mering, J. (1893). Beitrage zur Kenntniss der antipyretica. Ther Monatsch, 7, 577-587.
Warner, T. D., & Mitchell, J. A. (2004). Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. The FASEB journal, 18(7), 790-804.
Wilkes, J. M., Clark, L. E., & Herrera, J. L. (2005). Acetaminophen overdose in pregnancy. Southern medical journal, 98(11), 1118-1123. DOI:
https://doi.org/10.1097/01.smj.0000184792.15407.51
Williams, L. J., Pasco, J. A., Henry, M. J., Sanders, K. M., Nicholson, G. C., Kotowicz, M. A., & Berk, M. (2011). Paracetamol (acetaminophen) use, fracture and bone mineral density. Bone, 48(6), 1277-
1281. DOI: https://doi.org/10.1016/j.bone.2011.03.435
Wyskiel, M. (1998). Influence of acetylsalicylic acid and paracetamol on embryonal and fetal development in Wistar rat (Doctoral dissertation, Ph. D. Thesis. Lublin: Medical University of Lublin).
Ziegler, E. E., Edwards, B. B., Jensen, R. L., Mahaffey, K. R., & Fomon, S. J. (1978). Absorption and retention of lead by infants. Pediatric research, 12(1), 29-34. DOI:
https://doi.org/10.1203/00006450-197801000-00008
Bertolini, A., Ferrari, A., Ottani, A., Guerzoni, S., Tacchi, R., & Leone, S. (2006). Paracetamol: new vistas of an old drug. CNS drug reviews, 12(3‐4), 250275. DOI: https://doi.org/10.1111/j.15273458.2006.00250.x
Botting, R. M. (2000). Mechanism of action of acetaminophen: is there a cyclooxygenase 3?. Clinical Infectious Diseases, 31(Supplement_5), S202-S210. DOI: https://doi.org/10.1086/317520
Burdan, F. (2003). Intrauterine growth retardation and lack of teratogenic effects of prenatal exposure to the combination of paracetamol and caffeine in Wistar rats. Reproductive Toxicology, 17(1), 51-58. DOI:
https://doi.org/10.1016/S0890-6238(02)00097-7
Cai, G., Zhu, J., Shen, C., Cui, Y., Du, J., & Chen, X. (2012). The effects of cobalt on the development, oxidative stress, and apoptosis in zebrafish embryos. Biological trace element research, 150(1-3),
200-207. DOI: https://doi.org/10.1007/s12011-0129506-6
Chandrathilaka, A. M. D. S., Ileperuma, O. A., & Hettiarachchi, C. V. (2013). Spectrophotometric and pH-metric studies on Pb (II), Cd (II), Al (III) and Cu (II) complexes of paracetamol and ascorbic acid. Journal of the National Science Foundation of Sri
Lanka, 41(4). DOI:
http://dx.doi.org/10.4038/jnsfsr.v41i4.6253
Conings, S., Tseke, F., Van den Broeck, A., Qi, B., Paulus, J., Amant, F., ... & Van Calsteren, K. (2019). Transplacental transport of paracetamol and its phase II metabolites using the ex vivo placenta perfusion model. Toxicology and applied pharmacology, 370,
14-23. DOI: https://doi.org/10.1016/j.taap.2019.03.004
Dharmage, S. C., & Allen, K. J. (2011). Does regular paracetamol ingestion increase the risk of developing asthma?. Clinical & Experimental
Allergy, 41(4), 459-460. DOI:
https://doi.org/10.1111/j.1365-2222.2011.03716.x
Eyers, S., Weatherall, M., Jefferies, S., & Beasley, R. (2011). Paracetamol in pregnancy and the risk of wheezing in offspring: a systematic review and metaanalysis. Clinical & Experimental Allergy, 41(4), 482489. DOI: https://doi.org/10.1111/j.1365-
2222.2010.03691.x
García-Martínez, O., Díaz-Rodríguez, L., Rodríguez-Pérez, L., De Luna-Bertos, E., Botella, C. R., & Ruiz, C. C. (2011). Effect of acetaminophen, ibuprofen and methylprednisolone on different parameters of human osteoblast-like cells. Archives of
Oral Biology, 56(4), 317-323. DOI: https://doi.org/10.1016/j.archoralbio.2010.10.018
Henderson, A. J., & Shaheen, S. O. (2013). Acetaminophen and asthma. Paediatric respiratory reviews, 14(1), 9-16. DOI: https://doi.org/10.1016/j.prrv.2012.04.004
Holm, J. B., Chalmey, C., Modick, H., Jensen, L. S., Dierkes, G., Weiss, T., ... & Koch, H. M. (2015). Aniline is rapidly converted into paracetamol impairing male reproductive development. Toxicological
Sciences, 148(1), 288-298. DOI: https://doi.org/10.1093/toxsci/kfv179
Igbinaduwa PO, Aghayere GE. (2015).
Determinatıon of lead in paracetamol oral liquıd dosage formulations in Nigeria. African Journal of Pharmaceutical Research & Development. Vol. 7 No.1; pp. 37-44.
Ilic, S., Drmic, D., Zarkovic, K., Kolenc, D., Coric, M., Brcic, L., ... & Ivica, M. (2010). High hepatotoxic dose of paracetamol produces generalized convulsions and brain damage in rats. A counteraction with the stable gastric pentadecapeptide BPC 157 (PL 14736). Journal of physiology and pharmacology, 61(2), 241.
James, L. P., Mayeux, P. R., & Hinson, J. A. (2003). Acetaminophen-induced hepatotoxicity. Drug metabolism and disposition, 31(12), 1499-1506. DOI:
https://doi.org/10.1124/dmd.31.12.1499 Karakuş, O., İlkaya, F., & Yılmaz, M. Z. (2013).
Parasetamol ve siklooksijenaz enzim inhibisyonu. Journal of Experimental and Clinical
Medicine, 30(1s), 9-14. DOI:
10.5835/jecm.omu.30.s1.002 Kaya S, Pirinçci İ, Bilgili A. (2002). Veteriner Hekimliğinde Toksikoli, 2nd edition,pp. 191-230. Medisan Publishing House, Ankara, TURKEY.
Lauwerys, R., & Lison, D. (1994). Health risks associated with cobalt exposure—an overview. Science of the Total Environment, 150(1-3), 1-6. DOI:
https://doi.org/10.1016/0048-9697(94)90125-2
Lawton, L. J., & Donaldson, W. E. (1991). Leadinduced tissue fatty acid alterations and lipid peroxidation. Biological trace element research, 28(2),
83. DOI: https://doi.org/10.1007/BF02863075
Lim, S. Y., Doherty, J. D., McBride, K., MillerIhli, N. J., Carmona, G. N., Stark, K. D., & Salem Jr, N. (2005). Lead exposure and (n-3) fatty acid deficiency during rat neonatal development affect subsequent spatial task performance and olfactory
discrimination. The Journal of nutrition, 135(5), 1019-
1026. DOI: https://doi.org/10.1093/jn/135.5.1019
Lubawy, W. C., & Garrett, R. B. (1977). Effects of aspirin and acetaminophen on fetal and placental growth in rats. Journal of pharmaceutical sciences, 66(1), 111-113. DOI:
https://doi.org/10.1002/jps.2600660129
Needleman, H. L., & Gatsonis, C. A. (1990). Lowlevel lead exposure and the IQ of children: a metaanalysis of modern studies. Jama, 263(5), 673-678. DOI: 10.1001/jama.1990.03440050067035 Nessa, F., Khan, S. A., & Shawish, K. A. (2016). Lead, cadmium and nickel contents of some medicinal agents. Indian journal of pharmaceutical sciences, 78(1), 111. DOI: https://dx.doi.org/10.4103%2F0250-474X.180260
Prescott L.F. (1996). Paracetamol (acetaminophen), 2nd edition. Taylor & Francis Ltd., London, UK.
Price, V. F., Miller, M. G., & Jollow, D. J. (1987). Mechanisms of fasting-induced potentiation of acetaminophen hepatotoxicity in the rat. Biochemical pharmacology, 36(4), 427-433. DOI:
https://doi.org/10.1016/0006-2952(87)90346-7
Rebordosa, C., Kogevinas, M., Bech, B. H., Sørensen, H. T., & Olsen, J. (2009). Use of acetaminophen during pregnancy and risk of adverse pregnancy outcomes. International journal of epidemiology, 38(3), 706-714. DOI:
https://doi.org/10.1093/ije/dyp151
Reel, J. R., Lawton, A. D., & LAMB IV, J. C. (1992). Reproductive toxicity evaluation of acetaminophen in Swiss CD-1 mice using a continuous breeding protocol. Toxicological Sciences, 18(2), 233-
239. DOI: https://doi.org/10.1093/toxsci/18.2.233
Robson, S. (2011). Pain relief in pregnancy. O&G Magazine, 13(1).
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(4), 495-507. DOI: https://doi.org/10.1016/j.reprotox.2010.07.007
Slattery, J. T., & Levy, G. (1979). Pharmacokinetic model of acetaminophen elimination. American journal of hospital pharmacy, 36(4), 440-444. DOI:
https://doi.org/10.1093/ajhp/36.4.440
Swierkosz, T. A., Jordan, L., McBride, M., McGough, K., Devlin, J., & Botting, R. M. (2002). Actions of paracetamol on cyclooxygenases in tissue and cell homogenates of mouse and rabbit. Medical Science Monitor, 8(12), BR496-BR503.
Şavlı, E. (2012). Paracetamol use in pregnancy,
Review. J Exp Clin Med; 29: 91-94. DOI:
10.5835/jecm.omu.29.02.002
Ulger H., & Pratten M. K. (1996). The effect of VEGF on embryonic development and yolk sac vascularisation. J Anat; 189(1): 239-243.
Vestergaard, P., Hermann, P., Jensen, J. E., Eiken, P., & Mosekilde, L. (2012). Effects of paracetamol, non-steroidal anti-inflammatory drugs, acetylsalicylic acid, and opioids on bone mineral density and risk of fracture: results of the Danish Osteoporosis Prevention
Study (DOPS). Osteoporosis International, 23(4), 1255-1265. DOI: https://doi.org/10.1007/s00198-0111692-0
Viberg, H., Eriksson, P., Gordh, T., & Fredriksson, A. (2014). Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters its analgesic and anxiolytic response in adult male mice. toxicological sciences, 138(1), 139-147. DOI:
https://doi.org/10.1093/toxsci/kft329
Von Mering, J. (1893). Beitrage zur Kenntniss der antipyretica. Ther Monatsch, 7, 577-587.
Warner, T. D., & Mitchell, J. A. (2004). Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. The FASEB journal, 18(7), 790-804.
Wilkes, J. M., Clark, L. E., & Herrera, J. L. (2005). Acetaminophen overdose in pregnancy. Southern medical journal, 98(11), 1118-1123. DOI:
https://doi.org/10.1097/01.smj.0000184792.15407.51
Williams, L. J., Pasco, J. A., Henry, M. J., Sanders, K. M., Nicholson, G. C., Kotowicz, M. A., & Berk, M. (2011). Paracetamol (acetaminophen) use, fracture and bone mineral density. Bone, 48(6), 1277-
1281. DOI: https://doi.org/10.1016/j.bone.2011.03.435
Wyskiel, M. (1998). Influence of acetylsalicylic acid and paracetamol on embryonal and fetal development in Wistar rat (Doctoral dissertation, Ph. D. Thesis. Lublin: Medical University of Lublin).
Ziegler, E. E., Edwards, B. B., Jensen, R. L., Mahaffey, K. R., & Fomon, S. J. (1978). Absorption and retention of lead by infants. Pediatric research, 12(1), 29-34. DOI:
https://doi.org/10.1203/00006450-197801000-00008
Published
2020-10-23
How to Cite
Seher Y., Y., A. Vugar A., T. Adem T., A. Şükrü, U. İlyas, and Y. Seher. 2020. “WHAT IS THE EFFECTS OF PARACETAMOL APPLIED AT DIFFERENT DOSES TO HEAVY METAL LEVELS IN RAT FETUS? ”. EurasianUnionScientists 2 (9(78), 9-16. https://doi.org/10.31618/ESU.2413-9335.2020.2.78.1008.
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