Fluorescent Egg White-Based Carbon Dots as a High-Sensitivity Iron Chelator for the Therapy of Nonalcoholic Fatty Liver Disease by Iron Overload in Zebrafish

Yu, Lidong; He, Mingyue; Si-han, Liu; Dou, Xinyue; Li, Li; Gu, Ning; Li, Bingsheng; Liu, Zhiguo; Wang, Guixue; Fan, Jianglin

doi:10.1021/acsami.1c14674

Cited by 28 publications

(41 citation statements)

References 67 publications

(96 reference statements)

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“…Interestingly, iron chelation reversed the levels of these lipid metabolismrelated genes and proteins, implicating that long-term iron overload might promote the synthesis of FFAs, whereas inhibit the consumption of FFAs in the liver, leading to more serious lipid metabolism disorder than NAFLD itself (Figure 7). Several studies also showed that hepatic iron deposition could play a role in the pathogenesis of NAFLD (33)(34)(35). In our study, both iron overload and high fat induced liver steatosis in Possible pathogenesis of NAFLD "multiple hit theory".…”

Section: Discussionsupporting

confidence: 63%

Iron overload accelerated lipid metabolism disorder and liver injury in rats with non-alcoholic fatty liver disease

et al. 2022

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Background/aimsNon-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Iron overload has been implicated in chronic non-communicable liver diseases, but its relationship with NAFLD remains unclear. This study aimed to investigate the underlying roles of iron overload in the development of NAFLD.MethodsMale Sprague Dawley rats were fed with a high-fat diet (HFD) and/or iron for 8, 12, and 20 weeks. Some rats fed with HFD plus iron also received intraperitoneal injection of deferoxamine (DFO) for 8 weeks. Liver steatosis, lipid metabolism and injury were evaluated.ResultsA NAFLD model, including typical liver steatosis, was established by feeding rats with a HFD, while iron overload alone is not enough to induce severe NAFL. Compared with rats fed a HFD, excess iron further increased lipid accumulation, serum levels of lipids, enzymes of liver function, and expression levels of CD36 and FAS in rat liver. In addition, iron overload decreased the activities of antioxidative enzymes in liver compared with HFD rats. The levels of CPT1 and the ratios of p-ACC/ACC were also decreased by iron overload. DFO effectively reversed the abnormal lipid metabolism and liver damage induced by a high-fat, high-iron diet.ConclusionA HFD plus iron overload might synergistically aggravate lipid metabolism disorders, liver injury, and oxidative damage, compared with a HFD alone. DFO might help to alleviate lipid metabolism dysfunction and improve the pathogenesis of NAFLD.

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Section: Discussionsupporting

confidence: 63%

Iron overload accelerated lipid metabolism disorder and liver injury in rats with non-alcoholic fatty liver disease

et al. 2022

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“…Current studies on the biology of Nano-ZnO are mainly focused on the antibacterial properties. Studies have shown that Nano-ZnO has antibacterial effects on both foodborne pathogens E. coli and Staphylococcus aureus , among which it is more sensitive to S. aureus [ 28 ]. Ofloxacin is a broad-spectrum antibacterial fluoroquinolone drug.…”

Section: Resultsmentioning

confidence: 99%

Double-Sided Nano-ZnO: Superior Antibacterial Properties and Induced Hepatotoxicity in Zebrafish Embryos

et al. 2022

Toxics

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Zinc oxide nanoparticles (Nano-ZnO) have been widely used in the food, cosmetics, and biomedical fields due to their excellent antibacterial and antioxidant properties. However, with the widespread application of Nano-ZnO, Nano-ZnO inevitably enters the environment and living organisms, causing harm to human health and ecosystem safety. Therefore, the biosafety and toxicological issues of Nano-ZnO are gradually being emphasized. Our study found that Nano-ZnO has superior antibacterial properties compared to ofloxacin in the fight against Staphylococcus aureus (S. aureus). Given that ofloxacin can inhibit bacterial-induced inflammation, we constructed a model of bacterial inflammation using S. aureus in zebrafish. We found that Nano-ZnO inhibited the NF-κB-mediated inflammatory signaling pathway. However, in the process, we found that Nano-ZnO caused hepatic steatosis in zebrafish. This suggested that Nano-ZnO had a certain hepatotoxicity, but did not affect liver development. Subsequently, we investigated the mechanism of hepatotoxicity produced by Nano-ZnO. Nano-ZnO triggered oxidative stress in the liver by generating ROS, which then induced endoplasmic reticulum stress to occur. It further activated srebp and its downstream genes fasn and acc1, which promoted the accumulation of fatty acid synthesis and the development of steatosis, leading to the development of nonalcoholic fatty liver disease (NAFLD). To address the hepatotoxicity of Nano-ZnO, we added carbon dots for the treatment of NAFLD. The carbon dots were found to normalize the steatotic liver. This provided a new strategy to address the hepatotoxicity caused by Nano-ZnO. In this work, we systematically analyzed the antibacterial advantages of Nano-ZnO in vivo and in vitro, explored the mechanism of Nano-ZnO hepatotoxicity, and proposed a new method to treat Nano-ZnO hepatotoxicity.

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“…[62] In 2018, Liu et al have designed probe 22 (Fe@EWCDs) based on an egg white-based carbon dots (EWCDs), which can bind low-concentration Fe 3 + (0-25 μM) with better chelating ability, thus achieving the fluorescence quenching detection of Fe 3 + . [63] Furthermore, they found that probe 22 could inhibit ROS production in the Fenton reaction owing to the chelation of cellular Fe 3 + , thereby inhibiting ER stress and hepatocyte apoptosis, and regulating adipocyte metabolism. In addition, probe 22 was successfully applied to alleviate iron overload-induced NAFLD in zebrafish by regulating the NF-kB signaling pathway downstream of the Nrf2 signaling pathway.…”

Section: Ions Probes With Fluorescence Imagingmentioning

confidence: 99%

Advances in Optical Imaging of Nonalcoholic Fatty Liver Disease

Shen

Zhou

et al. 2022

Chemistry An Asian Journal

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Nonalcoholic fatty liver disease (NAFLD), emerging as one of the most common chronic liver diseases including simple steatosis and non‐alcoholic steatohepatitis (NASH), is likely to progress to liver fibrosis and hepatic carcinoma if not treated in time. Therefore, early diagnosis and treatment of NAFLD are necessary. Currently, liver biopsy, as the gold standard for clinical diagnosis of NAFLD, is not widely accepted by patients due to its invasiveness. However, other non‐invasive methods that had been reported for NAFLD (such as magnetic resonance imaging, positron emission tomography, and ultrasound) still suffer from low resolution and sensitivity, which are available as a guide for liver biopsy sometimes. As a non‐invasive modality with high spatiotemporal resolution and superior sensitivity, optical imaging methods have been widely favored in recent years, mainly including fluorescence imaging, photoacoustic imaging, and bioluminescence imaging. With these optical imaging approaches, a series of optical probes based on optical and molecular‐specific design have been developed for the biomarker diagnosis and research of diseases. In this review, we summarize the existing non‐invasive optical imaging probes for the detection of biomarkers in NAFLD, including microenvironment (viscosity, polarity), ROS, RSS, ions, proteins, and nucleic acids. Design strategies for optical imaging probes and their applications in NAFLD bioimaging are discussed and focused on. We also highlight the potential challenges and prospects of designing new generations of optical imaging probes in NAFLD studies, which will further enhance the diversity, practicality, and clinical feasibility of NAFLD research.

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Fluorescent Egg White-Based Carbon Dots as a High-Sensitivity Iron Chelator for the Therapy of Nonalcoholic Fatty Liver Disease by Iron Overload in Zebrafish

Cited by 28 publications

References 67 publications

Iron overload accelerated lipid metabolism disorder and liver injury in rats with non-alcoholic fatty liver disease

Iron overload accelerated lipid metabolism disorder and liver injury in rats with non-alcoholic fatty liver disease

Double-Sided Nano-ZnO: Superior Antibacterial Properties and Induced Hepatotoxicity in Zebrafish Embryos

Advances in Optical Imaging of Nonalcoholic Fatty Liver Disease

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