Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Federal University of Espírito Santo, Vitória, ES, Brazil.
Postgraduate Program in Physiological Sciences, Department of Physiology, Federal University of Espírito Santo, Vitória, ES, Brazil.
Toxicology. 2022 Dec;482:153357. doi: 10.1016/j.tox.2022.153357. Epub 2022 Nov 2.
Forbidden in some countries due to its proven toxicity to humans, chlorpyrifos (CPF) still stands as an organophosphate pesticide (OP) highly used worldwide. Cardiotoxicity assessment is an unmet need in pesticide regulation and should be deeply studied through different approaches to better inform and generate an appropriate regulatory response to OP use. In the present study, we used our 4-week intermittent OP exposure model in rats to address the CPF effects on cardiac morphology allied with cardiovascular functional and biomolecular evaluation. Rats were intermittently treated with CPF at doses of 7 mg/kg and 10 mg/kg or saline (i.p.) and assessed for cardiac morphology (cardiomyocyte diameter and collagen content), cardiopulmonary Bezold-Jarisch reflex (BJR) function, cardiac autonomic tone, left ventricle (LV) contractility, cardiac expression of NADPH oxidase (Nox2), catalase (CAT), superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2) and cardiac levels of advanced oxidation protein products (AOPP) and thiobarbituric acid reactive substances (TBARS). Plasma butyrylcholinesterase (BuChE) and brainstem acetylcholinesterase (AChE) were also measured. Intermittent exposure to CPF induced cardiac hypertrophy, increasing cardiomyocyte diameter and collagen content. An impairment of cardioinhibitory BJR responses and an increase in cardiac vagal tone were also observed in CPF-treated animals without changes in LV contractility. CPF exposure increased cardiac Nox-2, CAT, SOD1, and TBARS levels and inhibited plasma BuChE and brainstem AChE activities. Our data showed that intermittent exposure to CPF induces cardiac hypertrophy together with cardiovascular reflex impairment, imbalance of autonomic tone and oxidative stress, which may bring significant cardiovascular risk to individuals exposed to OP compounds seasonally.
由于对人类具有已证实的毒性，氯吡硫磷（CPF）在一些国家被禁用，但它仍是全世界广泛使用的有机磷农药（OP）之一。在农药监管中，对其心脏毒性的评估是一个尚未满足的需求，应该通过不同的方法进行深入研究，以便更好地提供信息并对 OP 的使用做出适当的监管反应。在本研究中，我们使用了为期 4 周的大鼠间歇性 OP 暴露模型，研究 CPF 对心脏形态以及心血管功能和生物分子评估的影响。大鼠接受 7mg/kg 和 10mg/kg CPF 或生理盐水（ip）间歇性治疗，并评估心脏形态（心肌细胞直径和胶原蛋白含量）、心肺 Bezold-Jarisch 反射（BJR）功能、心脏自主神经张力、左心室（LV）收缩性、心脏 NADPH 氧化酶（Nox2）、过氧化氢酶（CAT）、超氧化物歧化酶 1（SOD1）、超氧化物歧化酶 2（SOD2）和心脏中高级氧化蛋白产物（AOPP）和硫代巴比妥酸反应物质（TBARS）的表达。还测量了血浆丁酰胆碱酯酶（BuChE）和脑干乙酰胆碱酯酶（AChE）。间歇性 CPF 暴露可诱导心脏肥大，增加心肌细胞直径和胶原蛋白含量。还观察到 CPF 处理动物的心脏抑制性 BJR 反应受损和心脏迷走神经张力增加，而 LV 收缩性没有变化。CPF 暴露增加了心脏 Nox-2、CAT、SOD1 和 TBARS 水平，并抑制了血浆 BuChE 和脑干 AChE 活性。我们的数据表明，间歇性 CPF 暴露可引起心脏肥大以及心血管反射受损、自主神经平衡失调和氧化应激，这可能会给季节性接触 OP 化合物的个体带来重大心血管风险。
