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全氟辛酸会导致鸡胚胎和雏鸡发育性心脏毒性。

Perflurooctanoic acid induces developmental cardiotoxicity in chicken embryos and hatchlings.

机构信息

Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, United States.

Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, United States.

出版信息

Toxicology. 2012 Mar 11;293(1-3):97-106. doi: 10.1016/j.tox.2012.01.005. Epub 2012 Jan 18.

Abstract

Perfluorooctanoic acid (PFOA) is a widespread environmental contaminant that is detectable in serum of the general U.S. population. PFOA is a known developmental toxicant that induces mortality in mammalian embryos and is thought to induce toxicity via interaction with the peroxisome proliferator activated receptor alpha (PPARα). As the cardiovascular system is crucial for embryonic survival, PFOA-induced effects on the heart may partially explain embryonic mortality. To assess impacts of PFOA exposure on the developing heart in an avian model, we used histopathology and immunohistochemical staining for myosin to assess morphological alterations in 19-day-old chicken embryo hearts after PFOA exposure. Additionally, echocardiography and cardiac myofibril ATPase activity assays were used to assess functional alterations in 1-day-old hatchling chickens following developmental PFOA exposure. Overall thinning and thinning of a dense layer of myosin in the right ventricular wall were observed in PFOA-exposed chicken embryo hearts. Alteration of multiple cardiac structural and functional parameters, including left ventricular wall thickness, left ventricular volume, heart rate, stroke volume, and ejection fraction were detected with echocardiography in the exposed hatchling chickens. Assessment of ATPase activity indicated that the ratio of cardiac myofibril calcium-independent ATPase activity to calcium-dependent ATPase activity was not affected, which suggests that developmental PFOA exposure may not affect cardiac energetics. In summary, structural and functional characteristics of the heart appear to be developmental targets of PFOA, possibly at the level of cardiomyocytes. Additional studies will investigate mechanisms of PFOA-induced developmental cardiotoxicity.

摘要

全氟辛酸(PFOA)是一种广泛存在于环境中的污染物,在美国普通人群的血清中均可检测到。PFOA 是一种已知的发育毒物,可导致哺乳动物胚胎死亡,其毒性被认为是通过与过氧化物酶体增殖物激活受体α(PPARα)相互作用而产生的。由于心血管系统对胚胎存活至关重要,因此 PFOA 对心脏的影响可能部分解释了胚胎死亡率。为了评估在禽类模型中 PFOA 暴露对心脏发育的影响,我们使用组织病理学和肌球蛋白免疫组织化学染色来评估 PFOA 暴露后 19 日龄鸡胚心脏的形态变化。此外,还使用超声心动图和心肌纤维 ATP 酶活性测定来评估发育性 PFOA 暴露后 1 日龄孵化小鸡的心脏功能变化。在 PFOA 暴露的鸡胚心脏中,观察到右心室壁的整体变薄和肌球蛋白致密层变薄。在暴露的孵化小鸡中,超声心动图检测到多个心脏结构和功能参数的改变,包括左心室壁厚度、左心室容积、心率、每搏量和射血分数。ATP 酶活性评估表明,心肌纤维钙非依赖性 ATP 酶活性与钙依赖性 ATP 酶活性的比值不受影响,这表明发育性 PFOA 暴露可能不会影响心脏能量代谢。总之,心脏的结构和功能特征似乎是 PFOA 的发育靶标,可能在心肌细胞水平。进一步的研究将探讨 PFOA 诱导的发育性心脏毒性的机制。

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