Przepiórska-Drońska Karolina, Łach Andrzej, Pietrzak-Wawrzyńska Bernadeta Angelika, Rzemieniec Joanna, Kajta Małgorzata, Wawrzczak-Bargieła Agnieszka, Bilecki Wiktor, Noworyta Karolina, Wnuk Agnieszka
Laboratory of Neuropharmacology and Epigenetics, Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland.
Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy.
Toxics. 2024 Dec 13;12(12):906. doi: 10.3390/toxics12120906.
Benzophenone-3 (BP-3), commonly used as a UV filter in personal care products and as a stabilizer, is an alleged endocrine disruptor with potential neurodevelopmental impacts. Despite its abundance in the environment, the studies on its effect on brain development are scarce, especially in terms of multigenerational impact. In this work, for the first time, we examined neurotoxic and pro-apoptotic effects of BP-3 on mouse brain regions (cerebral cortex and hippocampus) in both the first (F) and second (F) generations after maternal exposure to environmentally relevant BP-3 levels. We found disregulated markers of cell damage (LDH, HO, caspase-3 and -8) and observed increased expression of pro-apoptotic /FAS or /FASL. BP-3 exposure disrupted the BAX/BCL2 pathway, showing stronger effects in the F than in the F generation, with a dominance of extrinsic pathway (FAS, FASL, caspase-8) over intrinsic one (BAX, BCL2), suggesting that BP-3-induced apoptosis primarily operates via the extrinsic pathway and could impair brain homeostasis across generations. This study underscores the potential of BP-3 to increase multigenerational risks associated with disrupted neurodevelopment and highlights the importance of understanding its long-term neurotoxic effects.
二苯甲酮-3（BP-3）常用作个人护理产品中的紫外线过滤剂和稳定剂，是一种据称具有内分泌干扰作用且可能影响神经发育的物质。尽管它在环境中广泛存在，但关于其对大脑发育影响的研究却很匮乏，尤其是在多代影响方面。在这项研究中，我们首次检测了母体暴露于环境相关水平的BP-3后，第一代（F1）和第二代（F2）小鼠大脑区域（大脑皮层和海马体）中BP-3的神经毒性和促凋亡作用。我们发现细胞损伤标志物（乳酸脱氢酶、血红素加氧酶、半胱天冬酶-3和-8）失调，并观察到促凋亡因子/FAS或/FASL的表达增加。BP-3暴露破坏了BAX/BCL2途径，在F1代中的影响比F2代更强，外在途径（FAS、FASL、半胱天冬酶-8）比内在途径（BAX、BCL2）占主导地位，这表明BP-3诱导的细胞凋亡主要通过外在途径发生，并且可能跨代损害大脑内环境稳态。这项研究强调了BP-3增加与神经发育紊乱相关的多代风险的可能性，并突出了了解其长期神经毒性作用的重要性。
