Assessment of Dexketoprofen Trometamol on Tibia Development in Chicken Embryos
Abstract
Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed analgesics, but their teratogenic potential remains understudied. Dexketoprofen trometamol (DT), commonly used clinically, lacks sufficient data con-cerning fetal skeletal development safety. This study investigated the effects of DT on tibial growth and growth plate structure in chicken embryos.
Methods: The experiment had two phases. Initially, embryos were administered either saline solution (control) or 0.084 mg/0.1 mL DT. In the second phase, embryos were divided into five groups: minimum DT dose (0.042 mg), maximum DT dose (0.126 mg), double maximum dose (0.252 mg), alcohol control, and saline control. Eggs were incubated for seven days before morphometric and histopathological analyses. Statistical tests included Fisher's exact test, one-way ANOVA, and Kruskal–Wallis analysis.
Results: In phase one, embryo viability at day 7 showed no significant difference between DT and control groups. In the second phase, embryos receiving minimum and maximum DT doses demonstrated improved developmental outcomes compared to the double maximum dose and control groups. Specifically, crown–rump lengths significantly increased in the maximum dose compared to the double maximum group (p=0.015). Tibial lengths were also superior in the maxi-mum dose group compared to saline controls. Growth plate proliferative zone cell counts were higher in minimum and maximum dose groups versus controls, notably exceeding the double maximum dose group. No significant changes appeared in tibia diameter, ossification center length, or hypertrophic zone cell counts.
Conclusion: DT showed no harmful impact on chicken embryo tibial development at the adult recommended dose in viable embryos. These findings also provide insight into the potential risk of embryotoxic effects of DT, particularly at supratherapeutic exposure levels where growth-related endpoints were less favorable. However, further molecular and clinical investigations are necessary.
Keywords
Bone Development, Abnormalities, Drug-induced, Embryo development, Dexketoprofen Trometamol, Tibia
Supporting Institution
No funding was received for this study.
Ethical Statement
This study was carried out with the approval of the Local Ethics Com-mittee for Animal Experiments at the Faculty of Agriculture, Kah-ramanmaras Sütcü İmam University (KSU-(Date:21.02.2020-Num-ber:2020/02-03). All necessary procedures were conducted at the Poultry Research Laboratory, Department of Animal Science, Faculty of Agriculture. The macroscopic and histopathological assessments used in this study were performed at the Department of Medical Patholo-gy, Tayfur Ata Sokmen Faculty of Medicine Hospital, Mustafa Kemal University.
Thanks
There are no acknowledgements.
References
- Moore KL, Persaud TVN, Torchia MG. The Developing Human: Clinically Oriented Embryology. 9th ed. Philadelphia, PA: Saunders; 2011.
- Schaefer C, Peters PWJ, Miller RK, editors. Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment. 3rd ed. Amsterdam: Academic Press; 2014.
- Van Gelder MM, Van Rooij IA, Miller RK, Zielhuis GA, de Jong-van den Berg LT, Roeleveld N. Teratogenic mechanisms of medical drugs. Hum Reprod Update. 2010;16(4):378-94.
- Vaudin P, Augé C, Just N, Mhaouty-Kodja S, Mortaud S, Pillon D. When pharmaceutical drugs become environmental pollutants: Potential neural effects and underlying mechanisms. Environ Res. 2022;205:112495.
- Werler MM, Mitchell AA, Hernandez-Diaz S, Honein MA. Use of over-the-counter medications during pregnancy. Am J Obstet Gynecol. 2005;193(3 Pt 1):771-7.
- Koren G, Florescu A, Costei AM, Boskovic R, Moretti ME. Non-steroidal anti-inflammatory drugs during third trimester and the risk of premature closure of the ductus arteriosus: a meta-analysis. Ann Pharmacother. 2006;40(5):824-9.
- Ofori B, Oraichi D, Blais L, Rey E, Bérard A. Risk of congenital anomalies in pregnant users of non-steroidal anti-inflammatory drugs: A nested case-control study. Birth Defects Res B Dev Reprod Toxicol. 2006;77(4):268-79.
- Antonucci R, Zaffanello M, Puxeddu E, Porcella A, Cuzzolin L, Dolores Pilloni M, et al. Use of non-steroidal anti-inflammatory drugs in pregnancy: impact on the fetus and newborn. Curr Drug Metab. 2012;13(4):474-90.
- U.S. Food and Drug Administration. FDA recommends avoiding use of NSAIDs in pregnancy at 20 weeks or later because they can result in low amniotic fluid. FDA Drug Saf Commun. 2020 Oct 15:1-9.
- Chambers CD, Tutuncu ZN, Johnson D, Jones KL. Human pregnancy safety for agents used to treat rheumatoid arthritis: adequacy of available information and strategies for developing post-marketing data. Arthritis Res Ther. 2006;8(4):215.