The first subacute study with oral administration of bisphenol AP in male rats: Cardiovascular data and metabolite detection

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety Pub Date : 2025-10-01 DOI:10.1016/j.ecoenv.2025.119143

Přemysl Mladěnka , Jaka Fadraersada , Patrícia Dias , Václav Tvrdý , Jana Pourová , Eduard Jirkovský , Alejandro Carazo , Catherine Gunaseelan , Patricia Harčárová , Zuzana Lomozová , Marija Sollner Dolenc , Jurij Trontelj , Lucija Peterlin Mašič

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Abstract

Bisphenols are frequently used in the plastic industry. However, there is a need for addressing their safety in in vivo studies based on the observed negative impact of bisphenol A. Bisphenol AP (BPAP) is frequently found in the environment, human food, and biological fluids, but its cardiovascular effects have not yet been tested. For this reason, we administered BPAP in a daily single dose of 2.5 mg.kg⁻¹ via oral gavage to eight male Wistar Han rats for a period of 4 weeks. Eight control rats received the solvent, sesame oil. Parent BPAP was detectable in plasma only in 3 animals by a validated LC-MS/MS method, whereas its glucuronide was found in all animals (48.4 ± 25.4 nM). Arterial blood pressure did not change during or at the end of the treatment. Some disturbances in cardiac rhythm were observed (e.g., increased heart rate, prolonged P wave and QT_peak interval, p < 0.05), but there was no increase in serum cardiac troponin T. Vessels isolated from BPAP-treated animals showed impaired vasodilatory response compared to control animals (p < 0.05). BPAP impacted coagulation and caused hemolysis only in hundreds of µM concentrations. These results demonstrate the potential of BPAP to affect cardiac rhythm and impair vessel homeostasis after subacute exposure.

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雄性大鼠口服双酚AP的首次亚急性研究：心血管数据和代谢物检测

双酚类物质经常用于塑料工业。然而，在观察到双酚a的负面影响的基础上，有必要在体内研究中解决它们的安全性问题。双酚AP （BPAP）经常存在于环境、人类食物和生物体液中，但其对心血管的影响尚未经过测试。因此，我们给药BPAP为每日单剂量2.5 mg。8只雄性Wistar Han大鼠灌胃，持续4周。8只对照大鼠给予溶剂、香油。经验证的LC-MS/MS方法仅在3只动物的血浆中检测到亲本BPAP，而在所有动物的血浆中均检测到其葡萄糖醛酸盐（48.4 ± 25.4 nM）。在治疗期间或治疗结束时，动脉血压没有变化。观察到一些心律紊乱（例如，心率增加，P波和QTpeak间期延长，P <； 0.05），但血清心肌肌钙蛋白t没有增加，与对照动物相比，bppa处理动物的血管分离显示血管舒张反应受损（P <； 0.05）。BPAP仅在数百μ M浓度下影响凝血并引起溶血。这些结果表明，BPAP在亚急性暴露后可能影响心律和损害血管稳态。

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来源期刊

Ecotoxicology and Environmental Safety 环境科学-毒理学

CiteScore

12.10

自引率

5.90%

发文量

1234

审稿时长

88 days

期刊介绍： Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.