Lipid metabolism disorders contribute to hepatotoxicity of ICR mice induced by nitrosamines exposure

Zhang, Hu; Lu, Lu; Zhao, Chunjiang; Liu, Qiwei; Zhou, Qian; Zhang, Ying; Pu, Yuepu; Wang, Shizhi; Liu, Ran; Yin, Lu

doi:10.1016/j.envint.2022.107423

Cited by 14 publications

(7 citation statements)

References 82 publications

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“…The normalized signal intensities of these lipids are represented with box plots in Figure E–H. The liver is a special organ for analyzing the distribution of lipids, which have irreplaceable functions in living cells, and lipid metabolism disorders could indicate toxicological effects in the liver . In the present study, hepatic lipid homeostasis was more easily disturbed by AgNSs than by the other two nanosilvers, and the variation in LPI(18:0) was extremely obvious in the livers of the AgNS-exposed group, which was in agreement with previous reports .…”

Section: Resultssupporting

confidence: 91%

Mass Spectrometry Imaging Reveals the Morphology-Dependent Toxicological Effects of Nanosilvers on Multiple Organs of Adult Zebrafish (Danio rerio)

Xie,

Li,

Chen

et al. 2024

Environ. Sci. Technol.

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Nanosilvers with multifarious morphologies have been extensively used in many fields, but their morphology-dependent toxicity toward nontarget aquatic organisms remains largely unclear. Herein, we used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to investigate the toxicological effects of silver nanomaterials with various morphologies on spatially resolved lipid profiles within multiple organs in adult zebrafish, especially for the gill, liver, and intestine. Integrated with histopathology, enzyme activity, accumulated Ag contents and amounts, as well as MSI results, we found that nanosilvers exhibit morphology-dependent nanotoxicity by disrupting lipid levels and producing oxidative stress. Silver nanospheres (AgNSs) had the highest toxicity toward adult zebrafish, whereas silver nanoflakes (AgNFs) exhibited greater toxicity than silver nanowires (AgNWs). Levels of differential phospholipids, such as PC, PE, PI, and PS, were associated with nanosilver morphology. Notably, we found that AgNSs induced greater toxicity in multiple organs, such as the brain, gill, and liver, while AgNWs and AgNFs caused greater toxicity in the intestine than AgNSs. Lipid functional disturbance and oxidative stress further caused inflammation and membrane damage after exposure to nanosilvers, especially with respect to sphere morphology. Taken together, these findings will contribute to clarifying the toxicological effects and mechanisms of different morphologies of nanosilvers in adult zebrafish.

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Section: Resultssupporting

confidence: 91%

Mass Spectrometry Imaging Reveals the Morphology-Dependent Toxicological Effects of Nanosilvers on Multiple Organs of Adult Zebrafish (Danio rerio)

Xie,

Li,

Chen

et al. 2024

Environ. Sci. Technol.

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“…Among the shared differential metabolites across the three HFPO-DA-treated groups, lipids and lipid-like molecules, such as heptadecanoyl carnitine, 7α-hydroxy-3-oxo-5β-cholan-24-oic acid, and three phosphatidylcholines (PCs), also predominated. PCs are closely associated with lipid homeostasis in both the liver and plasma, with previous lipidomic analyses highlighting changes in PC levels following liver injury. − Heptadecanoyl carnitine, an acylcarnitine, participates in fatty acid metabolism and is increasingly regarded as an important indicator in metabolic disease studies . Our results confirmed that serum levels of PCs and heptadecanoyl carnitine were significantly changed in mice after HFPO-DA exposure.…”

Section: Discussionsupporting

confidence: 84%

Kynurenic Acid Plays a Protective Role in Hepatotoxicity Induced by HFPO-DA in Male Mice

Hu,

Dai,

Sheng

2024

Environ. Sci. Technol.

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Following its introduction as an alternative to perfluorooctanoic acid, hexafluoropropylene oxide dimer acid (HFPO-DA) has been extensively detected in various environmental matrices. Despite this prevalence, limited information is available regarding its hepatotoxicity biomarkers. In this study, toxicokinetic simulations indicated that under repeated treatment, HFPO-DA in mice serum reached a steady state by the 4th day. To assess its subacute hepatic effects and identify potential biomarkers, mice were administered HFPO-DA orally at doses of 0, 0.1, 0.5, 2.5, 12.5, or 62.5 mg/kg/d for 7 d. Results revealed that the lowest observed adverse effect levels were 0.5 mg/kg/d for hepatomegaly and 2.5 mg/kg/d for hepatic injury. Serum metabolomics analysis identified 34, 58, and 118 differential metabolites in the 0.1, 0.5, and 2.5 mg/kg/d groups, respectively, compared to the control group. Based on weighted gene coexpression network analysis, eight potential hepatotoxicity-related metabolites were identified; among them, kynurenic acid (KA) in mouse serum exhibited the highest correlation with liver injury. Furthermore, liver-targeted metabolomics analysis demonstrated that HFPO-DA exposure induced metabolic migration of the kynurenine pathway from KA to nicotinamide adenine dinucleotide, resulting in the activation of endoplasmic reticulum stress and the nuclear factor kappa-B signaling pathway. Notably, pretreatment with KA significantly attenuated liver injury induced by HFPO-DA exposure in mice, highlighting the pivotal roles of KA in the hepatotoxicity of HFPO-DA.

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“…A large number of lysosomes needed to be degraded, and more energy was needed to help the reaction. Therefore, the oxidative decomposition of fatty acids provides energy but also aggravates the oxidative stress response of cells ( Zhang et al, 2022 ), forming a vicious circle. A large number of articles show that excessive oxidation and UPR can cause inflammatory reactions ( Feng et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Excessive sulfur oxidation in endoplasmic reticulum drives an inflammatory reaction of chondrocytes in aging mice

Zhang¹,

Li²,

Yuan³

et al. 2022

Front. Pharmacol.

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Osteoarthritis, as a common joint disease among middle-aged and elderly people, has many problems, such as diverse pathogenesis, poor prognosis and high recurrence rate, which seriously affects patients’ physical and mental health and reduces their quality of life. At present, the pathogenesis of osteoarthritis is not completely clear, and the treatment plan is mainly to relieve symptoms and ensure basic quality of life. Therefore, it is particularly urgent to explore the pathogenesis of osteoarthritis. Protein, as organic macromolecule which plays a major role in life activities, plays an important role in the development of disease. Through protein omics, this study found that with the increase of age, excessive sulfur oxidation occurred in endoplasmic reticulum of chondrocytes, which then drove the occurrence of inflammatory reaction, and provided a direction for the follow-up molecular targeted.

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Lipid metabolism disorders contribute to hepatotoxicity of ICR mice induced by nitrosamines exposure

Cited by 14 publications

References 82 publications

Mass Spectrometry Imaging Reveals the Morphology-Dependent Toxicological Effects of Nanosilvers on Multiple Organs of Adult Zebrafish (Danio rerio)

Mass Spectrometry Imaging Reveals the Morphology-Dependent Toxicological Effects of Nanosilvers on Multiple Organs of Adult Zebrafish (Danio rerio)

Kynurenic Acid Plays a Protective Role in Hepatotoxicity Induced by HFPO-DA in Male Mice

Excessive sulfur oxidation in endoplasmic reticulum drives an inflammatory reaction of chondrocytes in aging mice

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