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Crotonaldehyde paralyzes arteries by inducing impairment of ion channels, vascular histiocytic injury, overproduction of reactive oxygen species, mitochondrial damage, and autophagy.
Yang, Xiaomin; Xu, Xiaojia; Shi, Xiaowan; Wang, Yan; Hou, Xiaomin; Liu, Yu; Zhang, Mingsheng.
Affiliation
  • Yang X; Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, Shanxi Province 030001, China. Electronic address: yxm@d.sxmu.edu.cn.
  • Xu X; Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, Shanxi Province 030001, China. Electronic address: xxj@d.sxmu.edu.cn.
  • Shi X; Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, Shanxi Province 030001, China. Electronic address: shixiaowan@b.sxmu.edu.cn.
  • Wang Y; Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, Shanxi Province 030001, China. Electronic address: wangyan@sxmu.edu.cn.
  • Hou X; Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, Shanxi Province 030001, China. Electronic address: xiaominhou@sxmu.edu.cn.
  • Liu Y; Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, Shanxi Province 030001, China. Electronic address: yuliu@sxmu.edu.cn.
  • Zhang M; Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, Shanxi Province 030001, China. Electronic address: zms@sxmu.edu.cn.
Ecotoxicol Environ Saf ; 285: 117083, 2024 Sep 23.
Article in En | MEDLINE | ID: mdl-39317073
ABSTRACT
Humans are ubiquitously exposed to crotonaldehyde (CRA) endogenously and exogenously. Deeper knowledge of the pharmacological and toxicological characteristics and the mechanisms of CRA on vasculature is urgently needed for prevention of its harmfulness. The effects of acute and prolonged exposure to CRA were studied in rat isolated arteries and arterial smooth muscle cells (ASMCs). Instant exposure to CRA (1-300 µM) concentration-dependently declined the tension of pre-constricted arteries with an irreversible depression on the contractility. Prolonged exposure of rat coronary arteries (RCAs) to CRA concentration- and time-dependently depressed the arterial contractile responsiveness to various vasoconstrictors including depolarization, U46619, serotonin and Bay K8644 (an agonist of voltage-gated Ca2+ channels (VGCCs)). In fresh RCA ASMCs, CRA abated depolarization-induced elevation of intracellular Ca2+ ([Ca2+]i). Electrophysiological study revealed that acute exposure to CRA depressed the functions of Ca2+-activated Cl- channels (CaCCs), voltage-gated K+ (Kv) channels and inward rectifier K+ (Kir) channels in RCA ASMCs. Prolonged exposure of RCAs to CRA reduced the expressions of these ion channels in RCA ASMCs, disordered tissue frames, injured arterial cells, and increased autophagosomes in both ASMCs and endothelial cells. In rat aortic smooth muscle cells (A7r5), CRA exposure decreased the cell viability, elevated the intracellular levels of reactive oxygen species, reduced the mitochondrial membrane potential, and enhanced autophagy. Taken together, the present study for the first time portrays a clearer panoramic outline of the vascular effects and the mechanisms of CRA on arteries, demonstrates that CRA impairs arterial contractility, depresses VGCCs, CaCCs, Kv channels and Kir channels, reduces cell viability, and destroys the arterial histiocytes, and suggests that excessive oxidative stress, mitochondrial dysfunction and autophagy underlie these vascular damages. These findings are significant for the comprehensive evaluation of the vicious effects of CRA on arteries and suggest potential preventive strategies.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Ecotoxicol Environ Saf Year: 2024 Document type: Article Country of publication: Netherlands

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Ecotoxicol Environ Saf Year: 2024 Document type: Article Country of publication: Netherlands