Research Unit of Macromolecular Biochemistry and Genetics, Faculty of Sciences of Gafsa, 2112 Gafsa, Tunisia.
Sapienza University of Rome, Dept of Experimental Medicine, Syst Biol Grp Lab, Rome, Italy.
Ecotoxicol Environ Saf. 2021 Oct 1;222:112461. doi: 10.1016/j.ecoenv.2021.112461. Epub 2021 Jul 2.
This study characterized the impact of post-weaning high-fat diet (HFD) and/or permethrin (PER) treatment on heart dysfunction and fibrosis, as well as atherogenic risk, in rats by investigating interactions between HFD and PER. Our results revealed that HFD and/or PER induced remarkable cardiotoxicity by promoting cardiac injury, biomarker leakage into the plasma and altering heart rate and electrocardiogram pattern, as well as plasma ion levels. HFD and/or PER increased plasma total cholesterol, triacylglycerols, and low-density lipoprotein (LDL) cholesterol levels but significantly reduced high-density lipoprotein (HDL) cholesterol. Cardiac content of peroxidation malonaldehyde, protein carbonyls, and reactive oxygen species were remarkably elevated, while glutathione levels and superoxide dismutase, catalase and glutathione peroxidase activities were inhibited in animals receiving a HFD and/or PER. Furthermore, cardiac DNA fragmentation and upregulation of Bax and caspase-3 gene expression supported the ability of HFD and/or PER to induce apoptosis and inflammation in rat hearts. High cardiac TGF-β1 expression explained the profibrotic effects of PER either with the standard diet or HFD. Masson's Trichrome staining clearly demonstrated that HFD and PER could cause cardiac fibrosis. Additionally, increased oxidized LDL and the presence of several lipid droplets in arterial tissues highlighted the atherogenic effects of HFD and/or PER in rats. Such PER-induced cardiac and vascular dysfunctions were aggravated by and associated with a HFD, implying that obese individuals may be more vulnerable to PER exposure. Collectively, post-weaning exposure to HFD and/or PER may promote heart failure and fibrosis, demonstrating the pleiotropic effects of exposure to environmental factors early in life.
本研究通过探究高脂肪饮食（HFD）和/或氯菊酯（PER）处理之间的相互作用，研究了断奶后 HFD 和/或 PER 处理对大鼠心脏功能障碍和纤维化以及动脉粥样硬化风险的影响。我们的结果表明，HFD 和/或 PER 通过促进心脏损伤、生物标志物漏入血浆以及改变心率和心电图模式以及血浆离子水平，引起明显的心脏毒性。HFD 和/或 PER 增加了血浆总胆固醇、三酰甘油和低密度脂蛋白（LDL）胆固醇水平，但显著降低了高密度脂蛋白（HDL）胆固醇。动物接受 HFD 和/或 PER 后，心脏丙二醛、蛋白质羰基和活性氧的过氧化产物显著增加，而谷胱甘肽水平以及超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性受到抑制。此外，心脏 DNA 片段化和 Bax 和 caspase-3 基因表达上调支持 HFD 和/或 PER 在大鼠心脏中诱导凋亡和炎症的能力。高心脏 TGF-β1 表达解释了 PER 无论是在标准饮食还是 HFD 下引起的纤维化作用。Masson's Trichrome 染色清楚地表明，HFD 和 PER 可导致心脏纤维化。此外，动脉组织中增加的氧化型 LDL 和多个脂质滴突出了 HFD 和/或 PER 在大鼠中的动脉粥样硬化作用。PER 引起的心脏和血管功能障碍因 HFD 而加重，并与 HFD 相关，这表明肥胖个体可能更容易受到 PER 暴露的影响。总的来说，断奶后暴露于 HFD 和/或 PER 可能会促进心力衰竭和纤维化，表明早期暴露于环境因素的多效性作用。
