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Melatonin improved liver oxidative damage induced by PM2.5. (a) Production of ROS detected by the fluorescent probe DHE (magnification, 200; scale bar, 20 μm). (b) Quantitative analysis of ROS production is reflected by the mean fluorescence intensity as shown in different groups. (c) The level of MDA. (d) The level of 4-HNE. (e) The level of GSH-PX. (f) The vitality of SOD. (g) The mRNA expression of Nrf2, Keap1, and SOD. (h) Western blotting of Nrf2, Keap-1, and SOD. (i) Protein quantification of Nrf2. (j) Protein quantification of Keap1. (k) Protein quantification of SOD. All values are presented as the mean±SD (n=6). ∗P<0.05 for Con group vs PM2.5 group and #P<0.05 for PM2.5 group vs PM2.5+Mel group.
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Background:
Exposure to fine particulate matter (PM2.5) is associated with the risk of developing metabolic-associated fatty liver disease (MAFLD). Melatonin is the main secreted product of the pineal gland and has been reported to prevent hepatic lipid metabolism disorders. However, it remains uncertain whether melatonin could protect against PM2...
Citations
... Blood samples were collected by cardiac puncture when the rats were sacrificed to alleviate their suffering [37]. The plasma levels of total cholesterol, aspartate transaminase (AST), and alanine aminotransferase (ALT) were determined by a standard auto-analyzer (Hitachi model 7450, Tokyo, Japan). ...
Prenatal exposure to a high-fat diet (HFD) or microplastics can impact liver fat accumulation in offspring. This study investigates the protective effects of prenatal melatonin on liver injury in male pups resulting from maternal exposure to a HFD and microplastics. Pregnant Sprague-Dawley rats were fed either an HFD or a normal chow diet, with some groups exposed to microplastics alone or in combination with melatonin. Male pups were evaluated on postnatal day 7. Results indicated that pups in the HFD-microplastics group (HFD-Mi) exhibited increased liver lipid accumulation (observed in histological staining), apoptosis (elevated cleaved caspase 3, phospho-AKT, and TUNEL staining), inflammation (higher IL- 6 and TNF-α), and oxidative stress (elevated malondialdehyde). Conversely, melatonin treatment (HFD-Mi + M) significantly reduced these effects, including lipid accumulation, apoptosis, and inflammation, while enhancing antioxidant enzyme glutathione peroxidase activity and improving lipid metabolism (reduced SREBP- 1 expression). These findings suggest that prenatal melatonin mitigates liver injury caused by maternal HFD and microplastics through its anti-inflammatory, antioxidative, and lipid-regulating properties, underscoring its potential hepatoprotective role.
... An epidemiological study reveals that chronic exposure to PM 2.5 increases the incidence of MAFLD in China [8]. Another prospective cohort study indicates that the incidence of MAFLD is 34% higher in people living in areas with high PM 2.5 concentrations than in those with low PM 2.5 concentrations [9]. Consistent with epidemiological evidence, toxicological studies show that exposure to air pollutants can cause liver metabolic disorders and even liver cancer [10,11]. ...
... Consistent with epidemiological evidence, toxicological studies show that exposure to air pollutants can cause liver metabolic disorders and even liver cancer [10,11]. Du et al. found that PM 2.5 can induce hepatic steatosis in ApoE −/− mice [9]. Zheng et al. reported that mice exposed to ambient PM display non-alcoholic steatohepatitis (NASH)-like phenotypes and impaired liver glucose metabolism [12]. ...
Ambient particulate matter (PM2.5) is a potential risk factor for metabolic damage to the liver. Epidemiological studies suggest that elevated PM2.5 concentrations cause changes in hepatic metabolism, but there is a lack of laboratory evidence. Here, we aimed to evaluate the effects of PM2.5 exposure on liver metabolism in C57BL/6j female mice (10 months old) and to explore the mechanisms underlying metabolic alterations and differential gene expressions by combining metabolomics and transcriptomics analyses. The metabolomics results showed that PM2.5 exposure notably affected the metabolism of amino acids and organic acids and caused hepatic lipid and bile acid accumulation. The transcriptomic analyses revealed that PM2.5 exposure led to a series of metabolic pathway abnormalities, including steroid biosynthesis, steroid hormone biosynthesis, primary bile acid biosynthesis, etc. Among them, the changes in the bile acid pathway might be one of the causes of liver damage in mice. In conclusion, this study clarified the changes in liver metabolism in mice caused by PM2.5 exposure through combined transcriptomic and metabolomic analyses, revealed that abnormal bile acid metabolism is the key regulatory mechanism leading to metabolic-associated fatty liver disease (MAFLD) in mice, and provided laboratory evidence for further clarifying the effects of PM2.5 on body metabolism.
... Third, investigating pharmaceutical interventions for treating air pollution-induced MAFLD may benefit the working population subjected to prolonged ambient air pollution exposure. For instance, a study using ApoE-/-mice demonstrated that melatonin could inhibit the expression of protein tyrosine phosphatase 1B (PTP1B), triggered by PM 2.5 exposure, which is associated with weight gain and increased liver lipids (Du et al., 2022a). Another study suggested that total flavonoids could significantly reduce body weight, the liver-to-body weight ratio, and the surge in blood lipids induced by PM 2.5 (Jian et al., 2018). ...
Background: While evidence suggests that PM2.5 is associated with overall prevalence of Metabolic (dysfunction)-Associated Fatty Liver Disease (MAFLD), effects of comprehensive air pollutant mixture on MAFLD and its subtypes remain unclear.
Objective: To investigate individual and joint effects of long-term exposure to comprehensive air pollutant mixture on MAFLD and its subtypes.
Methods: Data of 27,699 participants of the Chinese Cohort of Working Adults were analyzed. MAFLD and subtypes, including overweight/obesity, lean, and diabetes MAFLD, were diagnosed according to clinical guidelines. Concentrations of NO3-, SO42-, NH4+, organic matter (OM), black carbon (BC), PM2.5, SO2, NO2, O3 and CO were estimated as a weighted average over participants' residential and work addresses for the three years preceding outcome assessment. Logistic regression and weighted quantile sum regression were used to estimate individual and joint effects of air pollutant mixture on presence of MAFLD.
Results: Overall prevalence of MAFLD was 26.6 % with overweight/obesity, lean, and diabetes MAFLD accounting for 92.0 %, 6.4 %, and 1.6 %, respectively. Exposure to SO42-, NO3-, NH4+, BC, PM2.5, NO2, O3and CO was significantly associated with overall MAFLD, overweight/obesity MAFLD, or lean MAFLD in single pollutant models. Joint effects of air pollutant mixture were observed for overall MAFLD (OR = 1.10 [95 % CI: 1.03, 1.17]), overweight/obesity (1.09 [1.02, 1.15]), and lean MAFLD (1.63 [1.28, 2.07]). Contributions of individual air pollutants to joint effects were dominated by CO in overall and overweight/obesity MAFLD (Weights were 42.31 % and 45.87 %, respectively), while SO42- (36.34 %), SO2 (21.00 %) and BC (12.38 %) were more important in lean MAFLD. Being male, aged above 45 years and smoking increased joint effects of air pollutant mixture on overall MAFLD.
Conclusions: Air pollutant mixture was associated with MAFLD, particularly the lean MAFLD subtype. CO played a pivotal role in both overall and overweight/obesity MAFLD, whereas SO42- were associated with lean MAFLD.
... A meta-analysis of 16 studies showed that when PM 2.5 increased by 10 µg/m 3 , the risk of liver cancer, liver cirrhosis, and fatty liver disease increased by 23 (95% CI: 14-33%), 17 (6-29%), and 51% (9-108%), respectively [84]. The increased risk of these diseases suggests that air pollution may lead to abnormal liver lipid metabolism, which has also been confirmed in some animal experiments [85][86][87]. Pathological accumulation of triglycerides and other lipids in hepatocytes is a feature of MAFLD [88]. The balance between synthesis and secretion of triglycerides in the liver is very important for the liver to maintain homeostasis of lipid metabolism. ...
Dyslipidemia is a critical factor in the development of atherosclerosis and consequent cardiovascular disease. Numerous pieces of evidence demonstrate the association between air pollution and abnormal blood lipids. Although the results of epidemiological studies on the link between air pollution and blood lipids are unsettled due to different research methods and conditions, most of them corroborate the harmful effects of air pollution on blood lipids. Mechanism studies have revealed that air pollution may affect blood lipids via oxidative stress, inflammation, insulin resistance, mitochondrial dysfunction, and hypothalamic hormone and epigenetic changes. Moreover, there is a risk of metabolic diseases associated with air pollution, including fatty liver disease, diabetes mellitus, and obesity, which are often accompanied by dyslipidemia. Therefore, it is biologically plausible that air pollution affects blood lipids. The overall evidence supports that air pollution has a deleterious effect on blood lipid health. However, further research into susceptibility, indoor air pollution, and gaseous pollutants is required, and the issue of assessing the effects of mixtures of air pollutants remains an obstacle for the future.
... Recent epidemiological studies and animal experiments have confirmed the occurrence of metabolic-associated fatty liver disease (MAFLD) induced by fine particulate matter (PM 2.5 ) exposure. MAFLD is associated with metabolic disorder, hepatic dysfunction, and liver dyslipidemia (Choe et al., 2019;Du et al., 2022b;Li et al., 2020a;Xu et al., 2019). Lipids are essential nutrients that help maintain energy homeostasis and form the constituents of cells and tissues. ...
... It is assumed that one of the risk factors for the onset and progression of NAFLD is air pollution, and the attention of researchers is directed to fine dust particles with a diameter of less than 2.5 µm (PM 2.5 ) [84]. A study by Du et al. [85] showed that in apoE −/− mice, melatonin 20 mg/kg/day orally for 4 weeks alleviated PM 2.5 -triggered hepatic steatosis and liver damage by regulating ROS-mediated protein tyrosine phosphatase1B (PTP1B) and nuclear factor erythroid 2-related factor (Nrf2) signaling pathways. Exposure to PM 2.5 resulted in liver steatosis (large lipid droplets, enlarged adipocytes, fatty degeneration) and oxidative stress (significantly increased values of MDA and 4-hydroxynonenal, increased activity of superoxide dismutase and glutathione peroxidase), which are alleviated by melatonin. ...
Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide, its complex pathogenesis remains incompletely understood. The currently stated hypotheses cannot fully clarify the interrelationships between individual pathogenetic mechanisms of the disease. No appropriate health strategies have been developed for treating NAFLD. NAFLD is characterized by an accumulation of triglycerides in hepatic cells (steatosis), with the advanced form known as nonalcoholic steatohepatitis. In the latter, superimposed inflammation can lead to fibrosis. There are scientific data on NAFLD’s association with components of metabolic syndrome. Hormonal factors are thought to play a role in the development of metabolic syndrome. Endogenous melatonin, an indoleamine hormone synthesized by the pineal gland mainly at night, is a powerful chronobiotic that probably regulates metabolic processes and has antioxidant, anti-inflammatory, and genomic effects. Extrapineal melatonin has been found in various tissues and organs, including the liver, pancreas, and gastrointestinal tract, where it likely maintains cellular homeostasis. Melatonin exerts its effects on NAFLD at the cellular, subcellular, and molecular levels, affecting numerous signaling pathways. In this review article, we discuss the experimental scientific data accumulated on the involvement of melatonin in the intimate processes of the pathogenesis of NAFLD.
Background:
Nonalcoholic fatty liver disease (NAFLD) is the extremely usual reason of chronic liver disease, extending from simple hepatic steatosis (HS), nonalcoholic steatohepatitis (NASH) to advanced hepatic fibrosis and cirrhosis. Though orlistat is a Food and Drug Administration (FDA) approved drug for long-duration management of obesity, few cases of severe hepatic insult were declared. Melatonin is an efficient antioxidant; it also regulates metabolic processes that lead to fat accumulation and obesity.
Aim of the work:
The current research aimed to compare the impact of orlistat, melatonin, and their combination on the structural changes of the hepatic tissue of adult male albino rats supplied with high fat diet (HFD).
Material and methods:
Thirty adult male albino rats divided into five groups. Liver specimens were divided into two parts. One-half was processed to obtain paraffin blocks, and the other half was processed to obtain semithin sections. Morphometric study and statistical analysis were done.
Results:
Hepatic tissue from the HFD group showed steatosis, ballooning, and inflammation and all these parameters were moderately improved - except for inflammation which worsened with therapy. Combined orlistat and melatonin-treated groups showed marked improvement of all parameters as well as marked improvement in the hepatic fibrosis.Orlistat/Melatonin combination therapy is both safe and effective in comparison to orlistat and melatonin monotherapy.
Aims
This study sought to explore the impact of Fusobacterium nucleatum on hepatic steatosis in apolipoprotein E (ApoE) knockout (KO) mice induced by a high‐fat diet (HFD) and elucidate the underlying mechanism.
Methods
ApoE KO mice, on a HFD, received F. nucleatum oral inoculation every other day. After 24 weeks, body weight, liver weight, and liver index were assessed. Serum biochemistry and pro‐inflammatory factors in serum and liver were analyzed. The histopathology of right maxilla and live were performed. Oil red O, immunohistochemistry, and immunofluorescence staining for the liver were conducted. Myeloperoxidase (MPO) activity, apoptosis, lipid reactive oxygen species (ROS), ROS, lipid peroxides, and hepatic lipids were also evaluated. Liver inflammation, fibrosis, de novo lipogenesis (DNL)‐related molecule, and Nrf2/Keap1‐related signaling molecule gene/protein expression were determined by real‐time PCR (RT‐PCR) and/or Western blot (WB) analysis.
Results
HFD‐fed ApoE KO mice infected by F. nucleatum demonstrated significant changes, including increased body and liver weight, elevated proinflammatory factors and lipids in serum and liver, as well as neutrophil infiltration, fibrosis, apoptosis, oxidative stress, and lipid peroxidation in the liver. Additionally, F. nucleatum stimulates hepatic lipid accumulation and activates de novo lipogenesis (DNL), while simultaneously suppressing the Nrf2/Keap1 antioxidant pathway.
Conclusion
In conclusion, our study reveals that oral inoculation of F. nucleatum might promote hepatic steatosis by inhibiting Nrf2/Keap1 pathway.
