KaydedilenlerDerginizi ekleyin

Dergiler / Ankara Üniversitesi Eczacılık Fakültesi Dergisi / 2026 / Cilt: 50 Sayı: 3

BENZOFENON-3’ÜN GELİŞİMSEL VE METABOLİK YOLAKLARA ODAKLANAN İN SİLİKO TOKSİSİTE PROFİLLEMESİ

IN SILICO TOXICITY PROFILING OF BENZOPHENONE-3 WITH FOCUS ON DEVELOPMENTAL AND METABOLIC PATHWAYS

Mehmethan Yıldırım(KIRŞEHİR AHİ EVRAN ÜNİVERSİTESİ)0009-0005-3263-6892
Neslihan Özdemir(KIRŞEHİR AHİ EVRAN ÜNİVERSİTESİ)0000-0001-6451-2863
Serap Yalcin Azarkan(KIRŞEHİR AHİ EVRAN ÜNİVERSİTESİ)0000-0002-9584-266X
Habibe Sema Arslan Unal(KIRSEHIR AHI EVRAN UNIVERSITY)0000-0002-2052-9345
Sayfa
555–568
Yayın Tarihi
2026-09-19
🏛️Bu makalenin bibliyografik verileri ve tam metin bağlantısı DergiPark üzerinden sağlanmıştır.
DergiPark Kaydı ↗
✨

Yapay Zeka Hızlı Bakış & Çıkarımlar

AI Insight
⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Sonuç ve Tartışma: Literatür verileri, BP-3’ün plasental bariyeri aşarak sistemik dolaşıma geçebildiğini göstermektedir.

📌 3 Maddede Bu Makale

🎯
Amaç & Hipotez:Amaç: Bu çalışma, kişisel bakım ürünlerinde yaygın olarak kullanılan bir ultraviyole (UV) filtresi olan Benzofenon-3’ün (BP-3) gelişimsel toksisite potansiyelini in siliko analizler kullanarak değerlendirmeyi amaçlamaktadır.
📊
Temel Bulgular & Veri:Gereç ve Yöntem: Benzofenon-3’ün toksikolojik özellikleri ProTox ve deTOX platformları kullanılarak tahmin edilmiştir.
💡
Sonuç & Katkı:Sonuç ve Tartışma: Literatür verileri, BP-3’ün plasental bariyeri aşarak sistemik dolaşıma geçebildiğini göstermektedir.
🔬Tür:Literatür & Derleme Çalışması
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Benzofenon-3 · gelişimsel toksisite · in siliko analiz

Özet

Amaç: Bu çalışma, kişisel bakım ürünlerinde yaygın olarak kullanılan bir ultraviyole (UV) filtresi olan Benzofenon-3’ün (BP-3) gelişimsel toksisite potansiyelini in siliko analizler kullanarak değerlendirmeyi amaçlamaktadır. Gereç ve Yöntem: Benzofenon-3’ün toksikolojik özellikleri ProTox ve deTOX platformları kullanılarak tahmin edilmiştir. Gelişimsel toksisite değerlendirmesi gebeliğin birinci, ikinci ve üçüncü trimester dönemleri için modellenmiştir. Ayrıca BP-3’ün insan sitokrom P450 enzimleri (CYP1A2, CYP2C19, CYP2D6) ile potansiyel etkileşimleri moleküler kenetlenme analizleri ile araştırılmıştır. Sonuç ve Tartışma: Literatür verileri, BP-3’ün plasental bariyeri aşarak sistemik dolaşıma geçebildiğini göstermektedir. In siliko analiz sonuçları, özellikle gebeliğin ikinci trimesterinde yüksek gelişimsel toksisite potansiyelini (olasılık: 0.952) ortaya koymuştur. Moleküler kenetlenme analizleri BP-3’ün CYP1A2’ye güçlü bağlanma afinitesi sergilediğini ve CYP2C19 ile CYP2D6 enzimleri ile anlamlı etkileşimler oluşturduğunu göstermiştir. Toksisite katkı haritalaması ise toksisite ile ilişkili spesifik moleküler bölgeleri desteklemiştir.

Abstract

Objective: This study aims to evaluate the developmental toxicity potential of Benzophenone-3 (BP-3), a widely used ultraviolet (UV) filter in personal care products, through in silico analyses. Material and Method: The toxicological properties of BP-3 were predicted using the ProTox and deTOX platforms. Developmental toxicity was modeled specifically for the first, second, and third trimesters of pregnancy. Additionally, the potential interactions of BP-3 with human cytochrome P450 enzymes (CYP1A2, CYP2C19, CYP2D6) were investigated via molecular docking analyses. Result and Discussion: Literature data confirm that BP-3 can cross the placental barrier and enter systemic circulation. In silico predictions indicated a high developmental toxicity potential, particularly during the second trimester (probability: 0.952). Molecular docking analyses revealed strong binding affinity of BP-3 to CYP1A2, as well as notable interactions with CYP2C19 and CYP2D6, suggesting possible interference with drug metabolism and endocrine regulation. The findings were further supported by structural toxicity contribution mapping, highlighting specific molecular regions responsible for toxicity.

🔖

Bu Makaleye Atıf Yap

Yıldırım, M., Özdemir, N., Azarkan, S. Y., Unal, H. S. A. (2026). BENZOFENON-3’ÜN GELİŞİMSEL VE METABOLİK YOLAKLARA ODAKLANAN İN SİLİKO TOKSİSİTE PROFİLLEMESİ. Ankara Üniversitesi Eczacılık Fakültesi Dergisi, Cilt: 50 Sayı: 3, 555–568. https://doi.org/10.33483/jfpau.1747733

📄 Tam Metin PDF Okuyucu

📄

PDF görüntüleyici hazırlanıyor...

Kaynakça (48)

  1. Yao, Y.N., Zhu, F., Li, X., et al. (2024). A review of sources, pathways, and toxic effects of human exposure to benzophenone ultraviolet light filters. Eco-Environment & Health, 3(1), 30-44. [CrossRef]
  2. Wnuk, W., Skórkowska, A., Wnuk, A. (2022). Benzophenone-3, a chemical UV-filter in cosmetics: Is it safe for children and pregnant women? Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 39(1), 26-33. [CrossRef]
  3. Warshaw, E.M., Ahmed, D.D., Belsito, D.V., et al. (2013). Patch test reactions associated with sunscreen products and the importance of testing to an expanded series: Retrospective analysis of North American Contact Dermatitis Group data, 2001 to 2010. Dermatitis, 24(4), 176-182. [CrossRef]
  4. Kim, Y., Tan, C.H., Chandra, A., et al. (2021). Photopatch testing in New Zealand: A 12-year retrospective review. Dermatitis, 32(1), 53-56. [CrossRef]
  5. Fediuk, D.J., Wang, Y., Xu, L., et al. (2010). Tissue deposition of the insect repellent DEET and the sunscreen oxybenzone from repeated topical skin applications in rats. International Journal of Toxicology, 29(6), 594-603. [CrossRef]
  6. Wnuk, A., Skórkowska, A., Krzyżanowska, W., et al. (2019). Prenatal exposure to benzophenone-3 impairs autophagy, disrupts RXRs/PPARγ signaling, and alters epigenetic and post-translational statuses in brain neurons. Molecular Neurobiology, 56(7), 4820-4837. [CrossRef]
  7. Skórkowska, A., Wnuk, A., Krzyżanowska, W., et al. (2020). Effect of combined prenatal and adult benzophenone-3 dermal exposure on factors regulating neurodegenerative processes, blood hormone levels, and hematological parameters in female rats. Neurotoxicity Research, 37(3), 683-701. [CrossRef]
  8. Schlumpf, M., Kypke, K., Wittassek, M., et al. (2010). Exposure patterns of UV filters, fragrances, parabens, phthalates, organochlor pesticides, PBDEs, and PCBs in human milk: Correlation of UV filters with use of cosmetics. Chemosphere, 81(10), 1171-1183. [CrossRef]
  9. Vilela, F.M.P., Fonseca, L.C., Gomes, B.A.Q., et al. (2016). Commercial sunscreen formulations: UVB irradiation stability and effect on UVB irradiation-induced skin oxidative stress and inflammation. Journal of Photochemistry and Photobiology B: Biology, 163, 413-420. [CrossRef]
  10. Heanue, T.A., Pachnis, V. (2007). Enteric nervous system development and Hirschsprung's disease: Advances in genetic and stem cell studies. Nature Reviews Neuroscience, 8(6), 466-479. [CrossRef]
  11. Rodríguez-Fuentes, G., Pacheco-Rosado, J., Olivares-Corichi, I.M., et al. (2015). Evaluation of the estrogenic and oxidative stress effects of the UV filter 3-benzophenone in zebrafish (Danio rerio) eleuthero-embryos. Ecotoxicology and Environmental Safety, 115, 14-18. [CrossRef]
  12. Xu, M., Zheng, D., Gong, S. (2021). Effects of low concentration benzophenone-3 exposure on the sex ratio and offspring development of zebrafish (Danio rerio). Bulletin of Environmental Contamination and Toxicology, 106(5), 740-746. [CrossRef]
  13. Kinnberg, K.L., Petersen, G.I., Albrektsen, M., et al. (2015). Endocrine-disrupting effect of the ultraviolet filter benzophenone-3 in zebrafish, Danio rerio. Environmental Toxicology and Chemistry, 34(12), 2833-2840. [CrossRef]
  14. Tao, J., Wang, M., Liu, S., et al. (2023). Embryonic benzophenone-3 exposure inhibited fertility in later-life female zebrafish and altered developmental morphology in offspring embryos. Environmental Science and Pollution Research, 30(17), 49226-49236. [CrossRef]
  15. Huo, W., Zhang, B., Liang, W., et al. (2016). The relationship between prenatal exposure to BP-3 and Hirschsprung's disease. Chemosphere, 144, 1091-1097. [CrossRef]
  16. Wang, J., Yang, J., Li, Y., et al. (2021). Benzophenone-3 induced abnormal development of enteric nervous system in zebrafish through MAPK/ERK signaling pathway. Chemosphere, 280, 130670. [CrossRef]
  17. Fu, J., Wang, T., Yu, H., et al. (2024). Prenatal exposure to benzophenone-type UV filters and the associations with neonatal birth outcomes and maternal health in south China. Environment International, 189, 108797. [CrossRef]
  18. Song, S., Gong, C., Duan, Y., et al. (2020). Occurrence and transfer of benzophenone-type ultraviolet filters from the pregnant women to fetuses. Science of The Total Environment, 726, 138503. [CrossRef]
  19. Mortensen, M.E., Calafat, A.M., Ye, X., et al. (2014). Urinary concentrations of environmental phenols in pregnant women in a pilot study of the National Children's Study. Environmental Research, 129, 32-38. [CrossRef]
  20. Polinski, K.J., Calafat, A.M., Ye, X., et al. (2018). Distribution and predictors of urinary concentrations of phthalate metabolites and phenols among pregnant women in the Healthy Start Study. Environmental Research, 162, 308-317. [CrossRef]
  21. Asimakopoulos, A.G., Thomaidis, N.S., Kannan, K. (2014). Widespread occurrence of bisphenol A diglycidyl ethers, p-hydroxybenzoic acid esters (parabens), benzophenone type-UV filters, triclosan, and triclocarban in human urine from Athens, Greece. Science of The Total Environment, 470-471, 1243-1249. [CrossRef]
  22. Banerjee, P., Eckert, A.O., Schrey, A.K., et al. (2018). ProTox-II: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 46(W1), W257-W263. [CrossRef]
  23. Banerjee, P., Gohlke, B.O., Preissner, R. (2024). ProTox 3.0: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 52(W1), W513-W520. [CrossRef]
  24. Broniowska, Ż., Wnuk, A., Krzyżanowska, W., et al. (2016). The effect of UV-filters on the viability of neuroblastoma (SH-SY5Y) cell line. NeuroToxicology, 54, 44-52. [CrossRef]
  25. Wnuk, A., Skórkowska, A., Krzyżanowska, W., et al. (2018). Benzophenone-3 impairs autophagy, alters epigenetic status, and disrupts retinoid X receptor signaling in apoptotic neuronal cells. Molecular Neurobiology, 55(6), 5059-5074. [CrossRef]
  26. Zhang, T., Sun, H., Kannan, K. (2013). Benzophenone-type UV filters in urine and blood from children, adults, and pregnant women in China: Partitioning between blood and urine as well as maternal and fetal cord blood. Science of The Total Environment, 461, 49-55. [CrossRef]
  27. Zhang, H., Gao, F., Chen, S., et al. (2022). Concentrations of bisphenols, benzophenone-type ultraviolet filters, triclosan, and triclocarban in the paired urine and blood samples from young adults: Partitioning between urine and blood. Chemosphere, 288, 132563. [CrossRef]
  28. Gao, C.J., Liu, L.Y., Ma, W.L., et al. (2015). Benzophenone-type UV filters in urine of Chinese young adults: concentration, source and exposure. Environmental Pollution, 203, 1-6. [CrossRef]
  29. Zhang, B., Zhang, T., Dong, Q., et al. (2018). Urinary benzophenone-type UV filters in people living in South China: Rural versus urban areas. Environmental Science: Processes & Impacts, 20(3), 553-560. [CrossRef]
  30. Castañer, O., Pintó, X., Subirana, I., et al. (2020). Remnant cholesterol, not LDL cholesterol, is associated with incident cardiovascular disease. Journal of the American College of Cardiology, 76(23), 2712-2724. [CrossRef]
  31. Santos-Baez, L.S., Ginsberg, H.N. (2020). Hypertriglyceridemia-causes, significance, and approaches to therapy. Frontiers in Endocrinology, 11, 616. [CrossRef]
  32. Tufféry, P., Murail, S. (2020). Samuelmurail/docking_py: Docking_py, a python library for ligand protein docking. Zenodo. [CrossRef]
  33. Murail, S., Pires, D.E.V., Blundell, T.L., et al. (2021). SeamDock: An interactive and collaborative online docking resource to assist small compound molecular docking. Frontiers in Molecular Biosciences, 8, 716466. [CrossRef]
  34. Kim, S., Choi, K. (2014). Occurrences, toxicities, and ecological risks of benzophenone-3, a common component of organic sunscreen products: A mini-review. Environment International, 70, 143-157. [CrossRef]
  35. Zhang, Y., Gao, C., Liu, Y., et al. (2022). Environmental concentrations of benzophenone-3 disturbed lipid metabolism in the liver of clown anemonefish (Amphiprion ocellaris). Environmental Pollution, 317, 120792. [CrossRef]
  36. Carvalho, A.E.C., Pereira, B.P.S., Silva, I.V.D., et al. (2025). Benzophenone-3 (oxybenzone) in zebrafish: Histopathological and oxidative stress analysis. Xenobiotica, 55, 71-77. [CrossRef]
  37. Majhi, P., Rattan, R., Ghosh, R., et al. (2020). Effects of benzophenone-3 and propylparaben on estrogen receptor-dependent R-loops and DNA damage in breast epithelial cells and mice. Environmental Health Perspectives, 128, 117006. [CrossRef]
  38. Yan, S., Yang, X., Wang, J., et al. (2022). Environmentally relevant concentrations of benzophenones triggered DNA damage and apoptosis in male Chinese rare minnows (Gobiocypris rarus). Environment International, 164, 107260. [CrossRef]
  39. Wnuk, A., Krzyżanowska, W., Skórkowska, A., et al. (2018). Prenatal exposure to benzophenone-3 (BP-3) induces apoptosis, disrupts estrogen receptor expression and alters the epigenetic status of mouse neurons. Journal of Steroid Biochemistry and Molecular Biology, 182, 106-118. [CrossRef]
  40. Krzyżanowska, W., Wnuk, A., Skórkowska, A., et al. (2018). The effects of benzophenone-3 on apoptosis and the expression of sex hormone receptors in the frontal cortex and hippocampus of rats. Toxicology Letters, 296, 63-72. [CrossRef]
  41. Kerdivel, G., Habauzit, D., Pakdel, F. (2013). Estrogenic potency of benzophenone UV filters in breast cancer cells: Proliferative and transcriptional activity substantiated by docking analysis. PLoS ONE, 8, e59502. [CrossRef]
  42. Szulak, F., Wnuk, A., Krzyżanowska, W., et al. (2022). Benzophenones alter autophagy and ER stress gene expression in pancreatic beta cells in vitro. In Vitro Cellular & Developmental Biology - Animal, 58(10), 936-956. [CrossRef]
  43. Cotrina, E., Cauli, O., Miralles, V.J. (2022). Binding of common organic UV-filters to the thyroid hormone transport protein transthyretin using in vitro and in silico studies: Potential implications in health. Environmental Research, 214, 114836. [CrossRef]
  44. Han, X., Ma, J., Wang, L., et al. (2022). A metabolomic study on the effect of prenatal exposure to benzophenone-3 on spontaneous fetal loss in mice. Ecotoxicology and Environmental Safety, 233, 113347. [CrossRef]
  45. Song, S.M., Gong, C., Duan, Y., et al. (2020). Occurrence and transfer of benzophenone-type ultraviolet filters from the pregnant women to fetuses. Science of The Total Environment, 726, 138503. [CrossRef]
  46. Ma, J., Han, X., Zhao, H., Wang, L., Su, J., Wang, X. (2023). Safety of benzophenone-type UV filters: A mini review focusing on carcinogenicity, reproductive and developmental toxicity. Chemosphere, 326, 138455. [CrossRef]
  47. Matta, M.K., Zusterzeel, R., Pilli, N.R., et al. (2019). Effect of sunscreen application under maximal use conditions on plasma concentration of sunscreen active ingredients: A randomized clinical trial. Jama, 321(21), 2082-2091. [CrossRef]
  48. Morohoshi, K., Yamamoto, H., Kamata, R., et al. (2005). Estrogenic activity of 37 components of commercial sunscreen lotions evaluated by in vitro assays. Toxicology In Vitro, 19(4), 457-469. [CrossRef]