Silica nanoparticles induce cardiac injury and dysfunction via ROS/Ca2+/CaMKII signaling

Qi, Yi; Xu, Hailin; Li, Xueyan; Zhao, Xinying; Li, Yan; Zhou, Xianqing; Chen, Siyu; Shen, Ning; Chen, Rui; Li, Yanbo; Sun, Zhiwei; Guo, Caixia

doi:10.1016/j.scitotenv.2022.155733

Cited by 20 publications

(5 citation statements)

References 76 publications

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“…Once the balance of iron metabolism (iron uptake, utilization, storage, and recycling) was disrupted, the accumulated free iron ions might trigger the Fenton reaction, followed by the activation of lipoxygenases (LOX), the generation of lipid peroxides, and the resultant ferroptosis [ 58 , 71 ]. A few indicators for oxidative stress and lipid peroxidation have been detected among the SiNPs-induced myocardial toxicity investigations, e.g., elevated ROS and MDA, whilst loss in antioxidant ability [ 48 , 63 ]. Oxidative stress and lipid peroxidation were clearly seen in SiNPs-exposed rat heart and cardiomyocytes (Figs.…”

Section: Discussionmentioning

confidence: 99%

“…All slides were recorded through Pannoramic Digital Slide Scanner and analyzed by CaseViewer (3DHISTECH, Hungary) or Image J software (NIH, USA). Afterward, the myocardial injury was scored in light of the degrees and scope of histopathological lesions in the tissue sections [ 23 , 48 ]. The percentage of positive area and total tissue area in the full field was measured for semi-quantitative analysis of collagen hyperplasia and ROS accumulation.…”

Section: Methodsmentioning

confidence: 99%

“…Notwithstanding, the participation of ferroptosis in SiNPs-elicited cardiotoxicity remains unknown. Accumulated evidence confirms oxidative stress and lipid peroxidation responsible for the SiNPs-elicited myocardial death and ensuing cardiac dysfunction [ 39 , 48 ]. A few recent reports reveal the participation of ferroptosis in SiNPs-elicited toxicity on vascular endothelial cells [ 25 ], microglia [ 24 ], and hepatocytes [ 32 ] in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Ferroptosis contributing to cardiomyocyte injury induced by silica nanoparticles via miR-125b-2-3p/HO-1 signaling

Li,

Xu,

Zhao

et al. 2024

Part Fibre Toxicol

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Background Amorphous silica nanoparticles (SiNPs) have been gradually proven to threaten cardiac health, but pathogenesis has not been fully elucidated. Ferroptosis is a newly defined form of programmed cell death that is implicated in myocardial diseases. Nevertheless, its role in the adverse cardiac effects of SiNPs has not been described. Results We first reported the induction of cardiomyocyte ferroptosis by SiNPs in both in vivo and in vitro. The sub-chronic exposure to SiNPs through intratracheal instillation aroused myocardial injury, characterized by significant inflammatory infiltration and collagen hyperplasia, accompanied by elevated CK-MB and cTnT activities in serum. Meanwhile, the activation of myocardial ferroptosis by SiNPs was certified by the extensive iron overload, declined FTH1 and FTL, and lipid peroxidation. The correlation analysis among detected indexes hinted ferroptosis was responsible for the SiNPs-aroused myocardial injury. Further, in vitro tests, SiNPs triggered iron overload and lipid peroxidation in cardiomyocytes. Concomitantly, altered expressions of TfR, DMT1, FTH1, and FTL indicated dysregulated iron metabolism of cardiomyocytes upon SiNP stimuli. Also, shrinking mitochondria with ridge fracture and ruptured outer membrane were noticed. To note, the ferroptosis inhibitor Ferrostatin-1 could effectively alleviate SiNPs-induced iron overload, lipid peroxidation, and myocardial cytotoxicity. More importantly, the mechanistic investigations revealed miR-125b-2-3p-targeted HO-1 as a key player in the induction of ferroptosis by SiNPs, probably through regulating the intracellular iron metabolism to mediate iron overload and ensuing lipid peroxidation. Conclusions Our findings firstly underscored the fact that ferroptosis mediated by miR-125b-2-3p/HO-1 signaling was a contributor to SiNPs-induced myocardial injury, which could be of importance to elucidate the toxicity and provide new insights into the future safety applications of SiNPs-related nano products. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ferroptosis contributing to cardiomyocyte injury induced by silica nanoparticles via miR-125b-2-3p/HO-1 signaling

Li,

Xu,

Zhao

et al. 2024

Part Fibre Toxicol

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“…Oxidative stress was a key toxic mechanism involved in the adverse effects triggered by SiNPs [ [79] , [80] , [81] ]. Interestingly, oxidative stress was closely correlated with lipogenesis or lipolysis [ 82 ], and involved in pathological progression of MAFLD [ 83 ].…”

Section: Discussionmentioning

confidence: 99%

Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress

Abulikemu

Zhao

et al. 2023

Redox Biology

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“…It has been observed that nanoparticles could transfer from the lungs to other organs via the circulatory system by using fluorescein or radiolabeling techniques (Nemmar et al, 2001; Furuyama et al, 2009). In addition, Qi et al further suggested that silica nanoparticles might pass through the lungs into the circulatory system and be redistributed in the heart, causing myocardial damage and dysfunction (Du et al, 2019; Qi et al, 2022). Therefore, it was reasonable to assume that due to the smaller particle size and stronger transfer diffusion ability of cigarette filter silica, some of the particles could enter the circulatory system and then transit to other tissues, resulting in less exposure to the lungs, thus, avoiding more serious apoptosis and fibrosis of lung tissues.…”

Section: Discussionmentioning

confidence: 99%

Adverse effects of cigarette filter silica on lungs: Comparison with natural crystalline silica particles

Kang,

Li,

Wang

et al. 2023

Toxicol Ind Health

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As a common additive in cigarette filters, nanosilica has been implemented to reduce the release of harmful substances in cigarette smoke. However, the potential risk of occupational exposure for cigarette factory workers is unknown. We collected physical examination data from 710 cigarette factory workers to evaluate the adverse effects of cigarette filter silica exposure. We also established mouse models induced by cigarette filter silica and crystalline silica separately to compare the lung inflammation, pulmonary function, apoptosis, and fibrosis of the two models. Workers in the rolling and packing workshop exposed to cigarette filter silica had a higher rate of abnormal lung function (17.75%) than those in the cutting workshop (0.87%). Animal experiments showed that compared with the same dose of crystalline silica, cigarette filter silica resulted in higher levels of inflammatory factors in the bronchoalveolar lavage fluid (BALF) of mice at day 7, and lower levels of total lung capacity (TLC), inspiratory capacity (IC), vital capacity (VC), and forced vital capacity (FVC) in mice at day 28. Additionally, both exposed groups of mice showed increased levels of caspase 3, collagen I (Col-Ⅰ), α-smooth muscle actin (α-SMA) and hydroxyproline (HYP) in the lungs, as well as collagen accumulation and fibrous nodules at day 28, with no significant difference between the two groups. The results suggested that cigarette filter silica caused more severe early lung inflammation and late ventilation impairment than the same dose of crystalline silica. In the future, we need to pay more attention to nanosilica protection in cigarette factories to prevent pulmonary dysfunction in workers.

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Silica nanoparticles induce cardiac injury and dysfunction via ROS/Ca2+/CaMKII signaling

Cited by 20 publications

References 76 publications

Ferroptosis contributing to cardiomyocyte injury induced by silica nanoparticles via miR-125b-2-3p/HO-1 signaling

Ferroptosis contributing to cardiomyocyte injury induced by silica nanoparticles via miR-125b-2-3p/HO-1 signaling

Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress

Adverse effects of cigarette filter silica on lungs: Comparison with natural crystalline silica particles

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