scholarly journals Multi-Omics Integration to Reveal the Mechanism of Hepatotoxicity Induced by Dictamnine

2021 ◽  
Vol 9 ◽  
Author(s):  
Can Tu ◽  
Ziying Xu ◽  
Lichun Tian ◽  
Zihui Yu ◽  
Tieshang Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Weight Ratio ◽  
Control Group ◽  
High Dose ◽  
Down Regulation ◽  
Lipid Metabolism Disorder ◽  
Fatty Acid Binding ◽  
Female Mice ◽  
Metabolism Disorder

Herb-induced liver injury (HILI) has become a great concern worldwide due to the widespread usage of herbal products. Among these products is Dictamni Cortex (DC), a well-known Traditional Chinese Medicine (TCM), widely used to treat chronic dermatosis. Dictamni Cortex has drawn increasing attention because of its hepatotoxicity caused by the hepatotoxic component, dictamnine. However, the potential hepatotoxicity mechanism of dictamnine remains unclear. Therefore, this study aimed to use the multi-omics approach (transcriptomic, metabolomic, and proteomic analyses) to identify genes, metabolites, and proteins expressions associated with dictamnine-induced hepatotoxicity. A study on mice revealed that a high dose of dictamnine significantly increases serum aspartate aminotransferase (AST) activity, total bilirubin (TBIL), and direct bilirubin (DBIL) levels, the relative liver weight and liver/brain weight ratio in female mice (P < 0.05 and P < 0.01), compared to the normal control group. Liver histologic analysis further revealed a high dose of dictamnine on female mice caused hepatocyte vesicular steatosis characterized by hepatocyte microvesicles around the liver lobules. The expressed genes, proteins, and metabolites exhibited strong associations with lipid metabolism disorder and oxidative stress. Dictamnine caused increased oxidative stress and early hepatic apoptosis via up-regulation of glutathione S transferase a1 (GSTA1) and Bax/Bcl-2 ratio and down-regulation of the antioxidative enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase 1 (GPx-1). Besides, the up-regulation of Acyl-CoA synthetase long-chain family member 4 (ACSL4) and down-regulation of acetyl-coa acetyltransferase 1 (ACAT1) and fatty acid binding protein 1 (FABP-1) proteins were linked to lipid metabolism disorder. In summary, dictamnine induces dose-dependent hepatotoxicity in mice, which impairs lipid metabolism and aggravates oxidative stress.

scholarly journals Quercetin Improves Glucose and Lipid Metabolism of Diabetic Rats: Involvement of Akt Signaling and SIRT1

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jing Peng ◽  
Qingde Li ◽  
Keye Li ◽  
Li Zhu ◽  
Xiaoding Lin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Lipid Metabolism ◽  
Fasting Blood Glucose ◽  
Akt Signaling ◽  
Hepatic Glycogen ◽  
High Dose ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
Glucose And Lipid Metabolism ◽  
Quercetin Treatment

Glucose and lipid metabolism disorder in diabetes mellitus often causes damage to multiple tissues and organs. Diabetes mellitus is beneficially affected by quercetin. However, its concrete mechanisms are yet to be fully elucidated. In our study, diabetes was induced in Sprague-Dawley rats by STZ injection. The rats were randomly divided into normal control, diabetic model, low-dose quercetin treatment, high-dose quercetin treatment, and pioglitazone treatment groups. Fasting blood glucose was collected to evaluate diabetes. Immunohistochemistry and fluorometric assay were performed to explore SIRT1. Akt levels were measured through immunoprecipitation and Western blot. After 12 weeks of quercetin treatment, the biochemical parameters of glucose and lipid metabolism improved to varying degrees. Hepatic histomorphological injury was alleviated, and hepatic glycogen content was increased. The expression and activity of hepatic SIRT1 were enhanced, and Akt was activated by phosphorylation and deacetylation. These results suggested that the beneficial effects of quercetin on glucose and lipid metabolism disorder are probably associated with the upregulated activity and protein level of SIRT1 and its influence on Akt signaling pathway. Hence, quercetin shows potential for the treatment of glucose and lipid metabolism disorder in diabetes mellitus.

Gut microbiota characterization and lipid metabolism disorder found in PCB77-treated female mice

Toxicology ◽  
2019 ◽  
Vol 420 ◽  
pp. 11-20 ◽  
Author(s):  
Yulang Chi ◽  
Hongou Wang ◽  
Yi Lin ◽  
Yanyang Lu ◽  
Qiansheng Huang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Lipid Metabolism Disorder ◽  
Female Mice ◽  
Metabolism Disorder

Effects of spirulina supplementation on lipid metabolism disorder, oxidative stress caused by high-energy dietary in Hu sheep

Meat Science ◽  
2020 ◽  
Vol 164 ◽  
pp. 108094 ◽  
Author(s):  
Yaxu Liang ◽  
Yongjin Bao ◽  
Xiaoxiao Gao ◽  
Kaiping Deng ◽  
Shiyu An ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
High Energy ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
Hu Sheep

scholarly journals Dendrobium catenatum Lindl. Water Extracts Attenuate Atherosclerosis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jichun Han ◽  
Jing Dong ◽  
Rui Zhang ◽  
Xiaofeng Zhang ◽  
Minghan Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Lipid Metabolism ◽  
Adhesion Molecule ◽  
Plaque Formation ◽  
Cholesterol Accumulation ◽  
Lipid Metabolism Disorder ◽  
Water Extracts ◽  
Metabolism Disorder ◽  
Ea.Hy926 Cells

Objectives. Dendrobium catenatum Lindl. (DH) is a Chinese herbal medicine, which is often used to make tea to improve immunity in China. Rumor has it that DH has a protective effect against cardiovascular disease. However, it is not clear how DH can prevent cardiovascular disease, such as atherosclerosis (AS). Therefore, the purpose of this study is to study whether DH can prevent AS and the underlying mechanisms. Methods. Zebrafish larvae were fed with high-cholesterol diet (HCD) to establish a zebrafish AS model. Then, we used DH water extracts (DHWE) to pretreat AS zebrafish. The plaque formation was detected by HE, EVG, and oil red O staining. Neutrophil and macrophage counts were calculated to evaluate the inflammation level. Reactive oxygen species (ROS) activity, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity in zebrafish were measured to reflect oxidative stress. The cholesterol accumulation and the levels of lipid, triglyceride (TG), and total cholesterol (TC) were measured to reflect lipid metabolism disorder. Then, parallel flow chamber was utilized to establish a low shear stress- (LSS-) induced endothelial cell (EC) dysfunction model. EA.hy926 cells were exposed to LSS (3 dyn/cm2) for 30 min and treated with DHWE. The levels of ROS, SOD, MDA, glutathione (GSH), and glutathiol (GSSG) in EA.hy926 cells were analysed to determine oxidative stress. The release of nitric oxide (NO), endothelin-1 (ET-1), and epoprostenol (PGI2) in EA.hy926 cells was measured to reflect EC dysfunction. The mRNA expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in EA.hy926 cells was detected to reflect EC dysfunction inflammation. Results. The results showed that DHWE significantly reduced cholesterol accumulation and macrophage infiltration in early AS. Finally, DHWE significantly alleviate the lipid metabolism disorder, oxidative stress, and inflammation to reduce the plaque formation of AS zebrafish larval model. Meanwhile, we also found that DHWE significantly improved LSS-induced EC dysfunction and oxidative stress in vitro. Conclusion. Our results indicate that DHWE could be used as a prevention method to prevent AS.

scholarly journals Oxidative Stress Linked Organ Lipid Hydroperoxidation and Dysregulation in Mouse Model of Nonalcoholic Steatohepatitis: Revealed by Lipidomic Profiling of Liver and Kidney

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1602
Author(s):  
Yue Wu ◽  
Zhen Chen ◽  
Hirotoshi Fuda ◽  
Takayuki Tsukui ◽  
Xunzhi Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Nonalcoholic Steatohepatitis ◽  
Lipid Hydroperoxide ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
Nash Group ◽  
Prevalent Disease ◽  
Liver And Kidney ◽  
The Relationship

Nonalcoholic steatohepatitis (NASH) is a prevalent disease related to lipid metabolism disorder and oxidative stress. Lipid hydroperoxidation is known to be a critical driving force of various disorders and diseases. However, the combination of both intact and hydroperoxidized lipids in NASH has not yet been studied. In this work, the liver and kidney samples from NASH-model mice were comprehensively investigated by using the LC/MS-based lipidomic analysis. As a result, triglycerides showed the amount accumulation and the profile alteration for the intact lipids in the NASH group, while phosphatidylethanolamines, lysophosphatidylethanolamines, plasmalogens, and cardiolipins largely depleted, suggesting biomembrane damage and mitochondria dysfunction. Notably, the lipid hydroperoxide species of triglyceride and phosphatidylcholine exhibited a significant elevation in both the liver and the kidney of the NASH group and showed considerable diagnostic ability. Furthermore, the relationship was revealed between the lipid metabolism disturbance and the lipid hydroperoxide accumulation, which played a key role in the vicious circle of NASH. The present study suggested that the omics approach to the lipid hydroperoxide profile might be the potential diagnostic marker of NASH and other oxidative stress-related diseases, as well as the evaluative treatment index of antioxidants.

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