Alfarawati Obada, Ameredes Bill T
Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77555, United States.
Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77555, United States.
Respir Physiol Neurobiol. 2025 Oct;337:104461. doi: 10.1016/j.resp.2025.104461. Epub 2025 Jun 25.
Acrolein exposure in the lung was studied to determine the effect of acrolein on airway responsiveness and pulmonary mechanics, as measured by the forced oscillation technique (FOT), under conditions of airway activation by methacholine (MCh), as well as with no activation, using the negative pressure-driven forced expiratory (NPFE) maneuvers to assess quasi-static lung compliance. Direct intratracheal acrolein was applied to C57BL/6 J male mice in dosages of 0 (saline vehicle-only) or 4 mg/kg, with FOT and NPFE assessments made 48 hr post-acrolein administration. Our results suggest that lipid peroxidation may be a primary factor in the observed attenuated response of resistance of the respiratory system (Rrs) to MCh (25 % decrease), potentially due to the alteration of the lipid bilayer that contains the transmembrane muscarinic receptors that respond to MCh. Furthermore, static lung compliance was significantly reduced in mice receiving acrolein. The product of lipid peroxidation, malondialdehyde (MDA), was confirmed in the bronchoalveolar lavage fluid (BALF) of the acrolein group to be significantly higher than the control groups (35 % increase). The nitrite concentration measured in the acrolein group BALF was consistent with elevated levels of nitric oxide (NO) (∼50 % increase), and perhaps peroxynitrite, which could be additional nitrosative stress factors promoting lipid peroxidation in our acute model of acrolein toxicity. Furthermore, the decrease in glutathione peroxidase (GPx) (52 % decrease) that we observed suggested a significant reduction in endogenous antioxidant capacity, with the oxidative stress associated with increased lipid peroxidation resultant from acrolein exposure. We conclude that the lipid peroxidation and decline in redox capacity due to nitrosative stress induced by acrolein could be an important factor in modulation of pulmonary mechanics, airway remodeling, and bronchial responsiveness.
研究了肺部丙烯醛暴露情况，以确定在乙酰甲胆碱（MCh）激活气道的条件下以及未激活时，通过强迫振荡技术（FOT）测量，丙烯醛对气道反应性和肺力学的影响，并使用负压驱动的强迫呼气（NPFE）动作评估准静态肺顺应性。将直接气管内注射的丙烯醛以0（仅生理盐水载体）或4 mg/kg的剂量应用于C57BL/6 J雄性小鼠，在丙烯醛给药后48小时进行FOT和NPFE评估。我们的结果表明，脂质过氧化可能是观察到的呼吸系统阻力（Rrs）对MCh的反应减弱（降低25%）的主要因素，这可能是由于含有对MCh有反应的跨膜毒蕈碱受体的脂质双层发生了改变。此外，接受丙烯醛的小鼠的静态肺顺应性显著降低。在丙烯醛组的支气管肺泡灌洗液（BALF）中，脂质过氧化产物丙二醛（MDA）被证实显著高于对照组（增加35%）。在丙烯醛组BALF中测得的亚硝酸盐浓度与一氧化氮（NO）水平升高（约增加50%）一致，可能还有过氧亚硝酸盐，它们可能是在我们的丙烯醛毒性急性模型中促进脂质过氧化的额外亚硝化应激因素。此外，我们观察到的谷胱甘肽过氧化物酶（GPx）的降低（降低52%）表明内源性抗氧化能力显著下降，氧化应激与丙烯醛暴露导致的脂质过氧化增加有关。我们得出结论，丙烯醛诱导的亚硝化应激导致的脂质过氧化和氧化还原能力下降可能是调节肺力学、气道重塑和支气管反应性的重要因素。
