Liver Injury Caused by Psoraleae Fructus： A Review / 中国实验方剂学杂志

Psoraleae Fructus （PF） is a non-toxic Chinese herbal medicine， while the liver injury caused by PF has aroused wide concern in recent years. At present， animal experiments and in vitro studies have been carried out to explore the mechanism， targets， and toxic components of PF in inducing liver injury， which， however， have differences compared with the actual conditions in clinical practice， and there are still some potential hepatotoxic components and targets of PF that have not been discovered. With the continuous progress in systems biology， establishing the drug-induced liver injury model and the liver injury prediction model based on network toxicology can reduce the cost of animal experiments， improve the toxicity prediction efficiency， and provide new tools for predicting toxic components and targets. To systematically explain the characteristics of liver injury in the application of PF and explore the potential hepatotoxic components and targets of PF， we reviewed the related articles published by China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， and PubMed from 1962 to 2021 and analyzed the characteristics and influencing factors of liver injury caused by PF in the patients. Furthermore， we summarized the chemical components of PF and the components entering blood. By reviewing the mechanism， targets， and components of PF in inducing liver injury that were discovered by in vivo and in vitro experiments， we summarized the known compounds in PF that may cause liver injury. Finally， the current methods for building the prediction model of PF-induced liver injury were summarized， and the predicted toxic components and targets were introduced. The possible factors of PF in causing liver injury were explained from three aspects： clinical characteristics， preclinical studies， and computer-assisted network prediction， which provide a reference for predicting the risk of PF-induced liver injury.

Mechanisms underlying the toxicity of microplastics to mammals: a review / 预防医学

@#As a new type of environmental pollutants, microplastics are widely distributed in the global ecosystem, and ingestion of microplastics may produce a number of toxic effects. Based on currently available publications, this paper describes the main pathways of exposure to microplastics, and summarizes the toxic mechanisms of microplastics in mammals, including oxidative stress, inflammatory response, immune damage, imbalance of gut microbiota, energy metabolism disorder and DNA damage, so as to provide insights into elucidation of the toxic mechanism mechanisms and health risk assessment of microplastics.

Research progress on toxic mechanisms of cadmium sulfide nanomaterials / 上海预防医学

Cadmium sulfide nanoparticles are a new type of semiconductor nanomaterials used in many applications. Studies have shown that cadmium sulfide nanoparticles have toxic effects on the reproductive system， liver， and kidney of the body， and the toxicities are affected by various factors. This paper summarized the current research on the toxicity of cadmium sulfide nanoparticles at home and abroad， and reviewed the latest research progress on the mechanisms of its toxic effects and influencing factors.

Exosomes Derived from Hydroquinone-transformed Human Bronchial Epithelial Cells Inhibited Recipient Cell Apoptosis by transferring miR-221 / 生物医学与环境科学（英文）

Objective@#Although benzene is a confirmed environmental carcinogen, the mechanism of its carcinogenicity remains largely unclear. The suggested oncogene, miR-221, is elevated and plays important roles in various tumors, but its role in benzene-induced carcinogenesis remains unknown.@*Methods@#In the present study, we constructed hydroquinone (HQ, a representative metabolite of benzene with biological activity)-transformed malignant cell line (16HBE-t) and analyzed the level of miR-221 in it with qRT-PCR. Exosomes from 16HBE-t cells incubated with or without an miR-221 inhibitor were isolated by ultracentrifugation, characterized by transmission electron microscopy and laser scanning confocal microscope, and then transfected into 16HBE cells. The effects of exosomal miR-221 on apoptosis induced by HQ in recipient cells were determined using flow cytometry.@*Results@#The amount of miR-221 in 16HBE-t was significantly increased compared with controls. When recipient cells ingested exosomes derived from 16HBE-t, miR-221 was increased, and apoptosis induced by HQ was inhibited. Blocking miR-221 in 16HBE-t using an inhibitor did not significantly alter miR-221 or apoptosis in recipient cells.@*Conclusion@#Exosomal miR-221 secreted by 16HBE-t inhibits apoptosis induced by HQ in normal recipient cells.

Study on hepatotoxicity mechanism of Euodiae Fructus based on network pharmacology / 中草药

Objective: To screen the main hepatotoxic components, predict the target of active components, and explore the mechanism of liver toxicity of Euodiae Fructus (EF). Methods: According to TCMSP database, PubChem database Pharmmapper server and Uniprot KB database information, active constituents of EF were screened, and targets of hepatotoxicity were predicted. The active component-acting target network of EF was constructed by Cytoscape software, while the function and metabolic pathways of target genes were analyzed by KOBAS 3.0 database. Results: Network analysis results demonstrated that 147 potential hepatotoxic components from EF, accompanied with 49 targets like F2, PIM1, MMP13 and MAOB, connecting with cell metabolism, catalytic activity, stimulate the reaction pathways may be associated with EF’s liver toxic effects. Conclusion: Based on network pharmacology methodology, this paper disclosed that many potential toxic components in EF may interact with cell metabolism, catalytic activity and other pathways through multiple targets, leading to produce hepatotoxicity in vivo as a result, which can provide new clues for further researches of the hepatotoxicity mechanism study of EF.

Developmental toxicity of exposure to ambient fine particulate matter / 上海交通大学学报（医学版）

Domestic and foreign studies have shown that fine particulate matter (PM2.5) pollution is a major factor affecting human health. In addition to the direct impact on the respiratory and cardiovascular systems, PM2.5 exposure during pregnancy can directly affect the growth and development of offspring, manifested as cardiopulmonary dysfunction and cognitive disorder, various adverse pregnancy outcomes, abnormal organ development, and congenital defects. However, the mechanism underlying the developmental toxicity of PM2.5 is still unclear. This article reviews PM2.5-induced developmental toxicity based on epidemiological investigation and toxicological studies, which will provide references for further studies.

Study on Toxicity Mechanism of Aconitum carmichaeli Lipid-soluble Alkaloids to Adjuvant-induced Arthritis Model Rats Based on Plasma Metabolomics / 中国药房

OBJECTIVE：To study the toxicity mechanism of lipid-soluble alkaloids of Aconitum carmichaeli to adjuvant-induced arthritis （AIA） model rats. METHODS： Totally 40 rats were randomly divided into blank group （ultrapure water）， model group （ultrapure water） and A. carmichaeli lipid-soluble alkaloids low-dose and high-dose groups （12.5， 35 mg/kg）， with 10 rats in each group. Except for blank group， rats in other groups were given complete Freund’s adjuvant 0.1 mL on the right hind paw to induce AIA model. 19 d after modeling， they were given relevant medicine intragastrically， once a day. After 14 d of administration， endogenous metabolites were separated and identified from plasma by UPLC-LTQ/Orbitrap MS. Then， the collected data were analyzed by principal component analysis （PCA） and partial least squares-discriminant analysis （PLS-DA）. Variable importance projection （VIP）＞1 and P value （＜0.05） were used to screen differential metabolites in plasma. Retrieving the database of Kyoto Encyclopedia of Genes and Genomes according to the differential metabolites，the toxic mechanism of A. carmichaeli liposoluble alkaloids to AIA rats were speculated. RESULTS： A total of 57 plasma metabolites were indentified， and 11 differential metabolites such as L-proline， 6-hydroxynicotinic acid and adenosine were identified. After inducing AIA model， the plasma contents of L-proline and uridylic acid were decreased significantly （P＜0.05 or P＜0.01）， and the content of deoxycytidine was increased significantly （P＜0.01）. Low dose of A. carmichaeli lipid-soluble alkaloids could decrease the plasma contents of adenosine and L-proline in rats （P＜0.05 or P＜0.01）， while the plasma contents of deoxycholic acid was increased significantly （P＜0.05）. High dose of A. carmichaeli lipid-soluble alkaloids could decrease the plasma contents of 6-hydroxynicotinic acid， adenosine， carnitine， L-proline， N-formylaminobenzoic acid were decreased significantly （P＜0.05 or P＜0.01）， while the plasma contents of deoxycholic acid， L-arginine， deoxycytidine and L-lysine were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： The toxicity of low-dose of A. carmichaeli lipid-soluble alkaloids to AIA model rats is less； the toxicity of high-dose of A. carmichaeli lipid-soluble alkaloids to AIA model rats may be related to abnormal bile secretion， lysine biosynthesis and metabolic disorders of purine， pyrimidine， tryptophan， proline and arginine.

Comparison of hepatotoxicity and toxic mechanisms of matrine and oxymatrine using in vivo and in vitro models / 中国比较医学杂志

Objective To compare the hepatotoxicity of matrine (MT) and oxymatrine (OMT) and explore the severity and characteristics of their toxicity, and to preliminarily elucidate their toxic mechanisms. Methods Liver cell line LO-2 cells were treated with acetaminophen (APAP), matrine and oxymatrine for 24 h, and the IC values, the contents of enzymes in the liver cells, the pathological changes, the contents of malondialdehyde (MDA) and glutathione (GSH) and the cell apoptosis rate were detected. In addition, adult zebrafish were treated with APAP, matrine and oxymatrine for 96 h, and the LC50 values, the pathological morphology of the liver cells, the contents of MDA and GSH and the apoptosis rate were detected. Meanwhile, the expression of oxidative stress-related gene, zgc: 136383, and the apoptosis-related genes, EIF4EBP3 and zgc: 123120, was also detected. Results Matrine and oxymatrine had toxic effects on liver cells in vitro. The IC50 value of matrine was 5. 3 mmol/L, and that of oxymatrine was ＞ 19 mmol/L. The contents of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the liver cells treated with matrine or oxymatrine were increased, and the cells appeared swollen, with an increase in the MDA level and a decrease in the GSH level. The cell apoptosis rate was also increased (P ＜ 0. 05). Furthermore, matrine and oxymatrine had toxic effects on the zebrafish. The LC50 value of matrine was 0. 41 mmol/L, and that of oxymatrine was ＞3. 8 mmol/L. The hepatocytes of zebrafish treated with matrine and oxymatrine appeared vacuolization in a mild to moderate degree, with an increase of the MDA content and a decrease of the GSH content. The cell apoptosis rate was increased (P ＜0. 05 for all). Expression of the oxidative stress-related gene zgc: 136383 (P ＜ 0. 05) and the apoptosis-resistant gene EIF4EBP3 (P ＜ 0. 05) was down-regulated by matrine, but that of the apoptosis-promoting gene zgc: 123120 was up-regulated (P ＜ 0. 05). Conclusions Results of the experiments using liver cells in vitro are consistent with those using the in vivo zebrafish model. Matrine (MT) and oxymatrine (OMT) both have hepatotoxicity, with similar toxic characteristics, and the toxicity of matrine is greater than oxymatrine. The mechanism of their hepatotoxicity is related with oxidative stress and cell apoptosis. Matrine reduces lipid transportation and activates oxidative stress reactions through down-regulation of gene zgc: 136383. In addition, matrine induces apoptosis in the liver cells via up-regulation of the apoptosis-promoting gene zgc: 123120 and down-regulation of the apoptosis-resistant gene EIF4EBP3.

Gas Chromatography-Mass Spectrometry Analysis of Metabolic Profiling of Lung Tissues of Mice after Instillation of Fine Particulate Matter / 分析化学

A method based on gas chromatography-mass spectrometry (GC-MS) was established to analyze the changes of intracellular metabolites and study the toxic mechanisms of different concentrations of particulate matter (PM2.5) effecting the lung tissues in mice.Nasal drip experiments of PM2.5 suspensions (0, 7.5, 20.0, 37.5 g/L) for mice were carried out, and the intracellular metabolites in lung tissues were extracted, pretreated and analyzed.Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were employed for pattern recognition, and an obvious distinction among different conditions was found.According to the PLS-DA loading diagram and variable important factor (VIP) value, 7 kinds of potential biomarkers, alanine, valine, leucine, ornithine, fumaric acid, citric acid and purine (p<0.01), were determined with significant differences between four different concentrations of PM2.5.Metabolic pathway analysis indicated that the oxidative stress reactions were enhanced, and the TCA cycle and the purine metabolism in lung cells were restrained after dripping PM2.5 to the lung tissues in mice.This study could provide a new perspective and theoretical basis for the further analysis on toxic mechanisms by PM2.5.

Advances in methods and toxic mechanisms of rotenone-induced Parkinson disease models / 中国药理学与毒理学杂志

It is important to establish animal models of Parkinson disease (PD) similar to clinical features of human disease. Rotenone can readily penetrate the blood-brain-barrier and cytomem-branes due to its strong lipophilic ability. Rotenone models of PD can not only simulate behavioral changes in patients with PD, but also bear a strong resemblance to the human disease characteristics and pathological process of PD. Based on to researches at home and abroad in recent years, this paper summarizes and analyzes the modeling methods and toxic mechanisms of rotenone-induced PD. These methods include stereotaxis, intravenous injection, abdominal injection, subcutaneous injection, microdialysis drug, intragastric administration, subcutaneous embedded slow-release microspheres and exposure to drugs. The In vitro model invotves SH-SY5Y cells, PC12 cells and DA neurons. The toxic mechanisms involveα-synuclein abnormal aggregation, mitochondrial dysfunction, the generation of reactive oxygen species, damage to the antioxidant defense system, nerve cell apoptosis, and autophagy.

Advances in biomarkers of oxidative stress under sulfur mustard exposure / 军事医学

Sulfur mustard [bis (2-chloroethyl) sulfide, sulfur mustard, SM] is considered a powerful chemical warfare agent.There is still no specific antidote due to its complex toxicological mechanism .An intimate knowledge of the toxic mechanisms and pathophysiological changes is important to the treatment of sulfur mustard injury .Oxidative stress is one of the most important pathophysiological processes involved in the toxic effect of sulfur mustard .The study of oxidative stress biomarkers induced by sulfur mustard can help to reveal the role of oxidative stress in sulfur mustard intoxication , which may contribute to better understanding of the toxic mechanism and development of therapeutic measures after sulfur mustard exposure.The research advances in oxidative stress biomarkers in sulfur mustard intoxication are reviewed .