ENVIRONMENTAL RESEARCH
·
2021
·
IF 6.498
Ying Liu,Nan Lin,Cao Dai,Jianliang Xu,Yi Zhang,Mingxing Xu,Fei Wang,Yanjie Li,Da Chen
Per- and polyfluoroalkyl substances (PFASs) are anthropogenic compounds that are widely accumulated in human tissues, and the liver is considered a primary target organ for PFASs exposure. The occurrence and distribution of 21 PFASs in liver tissues with tumors (n = 55) and without tumors (n = 55) are investigated in this study. Eleven perfluorinated carboxylic acids (PFCAs) and five perfluorinated sulfonic acids (PFSAs) were detected at high frequencies (45.5%–100 %), while the detection frequencies of five perfluoroalkyl phosphate (PFPAs) were relatively lower (≤29.1 %). PFSAs and PFCAs accounted for up to 82.5%–92.7 % of the total PFASs. Although it was not found to be statistically significant, the concentrations of the total PFASs were slightly higher in the tumor liver samples (mean 64.3, range 5.70–303 ng/g) than those in the non-tumor liver samples (mean 62.7, range 4.08–240 ng/g).The perfluorooctanoic acid (PFOA), perfluorotridecanoic acid (PFTrDA), and perfluorobutanesulphonate (PFBS) showed significant differences (p < 0.05) between the tumor and non-tumor liver samples, and the different distribution levels of these three PFASs may have been a consequence of oxidative stress . The total concentrations of PFASs in the three age groups were in the decreasing order of middle-aged people (45–60) > old people (>60) > young people (<45). The PFASs in females were generally lower than in males, which may have been related to women's special excretion methods (such as childbirth and breastfeeding). The results should be valuable for further mechanistic studies regarding the toxic effects of PFASs in human livers.
研究领域:
环境科学
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毒理学
·
医学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
Lili Wu,Weichao Han,Yulian Chen,Tao Zhang,Junjin Liu,Shilong Zhong,Han Liu,Congcong Han,Zhongyi Zhang,Shuwen Liu,Lan Tang
Emodin is a main anthraquinone compound which exists in Chinese traditional medicines including Polygonum multiflorum and Rhubarb. It is documented to have obvious liver and kidney toxicity. This study aims to (a) estimate gender differences of the hepatotoxicity and toxicokinetics in rats after oral administration of emodin (60 and 150 mg/kg/d) for a consecutive 28 days and (b) clarify relative mechanisms caused by glucuronidation and disposition. Hepatotoxicity was significantly higher in female rats than that in male rats, as evidenced by histopathological and biochemical tests. Similarly, the toxicokinetic profiles of emodin have time and gender differences, which could cause time and gender differences in hepatotoxicity. The metabolic and transcriptomics data of 55 human liver and 36 human kidney samples demonstrated that UDP-glucuronosyltransferase 2B7 (UGT2B7) was the predominant enzyme for emodin glucuronidation. A genome-wide association study (GWAS) identified that rs11726899 located within ∼50 kb of the transcript of UGT2B could significantly affect emodin metabolism. Knockdown of UGT2B7 in HepG2 cells significantly decreased emodin glucuronidation and increased cytotoxicity of emodin. The gene expression and protein levels of UGT2B7 were decreased, but those of the multidrug-resistant-protein 2 (MRP2) were increased in HepG2 cells after being treated with 50 μM emodin for 48 h. Long-term use of emodin could decrease the intrinsic clearance (CLint, decreased by 18.5%–35.4%) values of zidovidue (UGT2B7 substrate) glucuronide in both male and female liver microsomes from rats administrated with emodin for 28 days, thus causing the accumulation of emodin. However, higher self-induced MRP2 expression and lower hepatotoxicity were observed in emodin-treated male rats compared to that in female rats. Therefore, gender differences in the hepatotoxicity and toxicokinetics of emodin are potentially mediated by the coupling of UGT2B7 and MRP2 in vivo.
研究领域:
药理学
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毒理学
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分子生物学
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DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 5
·e70068
·
IF 1.7
Sanwen Li,Qing Shao,Hongqun Qiao
Schisandrin B (Sch B), a natural lignan extracted from schisandra chinesis, has exhibited various pharmacological activities including anticancer effects. However, studies on the preclinical toxicokinetic profile of Sch B have not been publicly reported. This study aimed to investigate the preclinical concomitant toxicokinetics of multiple administration of Sch B. Sch B was administered orally to rats and dogs at 150, 300, and 600 mg/kg/day and 50, 100, and 200 mg/kg/day, respectively, for 26 weeks. Plasma concentrations of Sch B were determined by a validated HPLC–MS/MS method. According to the toxicokinetic results, significant gender differences were observed in the rats, and females had higher exposures than males for each dosing group. Toxicokinetic analysis demonstrated a notable accumulation in the plasma of dogs during the repeated administration of Sch B, and the degree of accumulation increased with the increase of the dose. The findings of this study indicated that there were differences in the concomitant toxicokinetics of Sch B between rats and dogs. These results can inform clinical studies and provide valuable insights for future human Sch B risk assessments.
研究领域:
药理学
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毒理学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
BMC PLANT BIOLOGY
·
2025
·Vol. 25
·期 1
·1-27
·
IF 4.8
Wang Pei-lu,You Jin-ling,Hua Qian-ming,Li Hua-qiang,Shi Qi,Li Wen-long,Sheng Yun-jie,Liu Kao-hua,He Bing-qian,Zhang Qiao-yan,Qin Lu-ping,Meng Xiong-yu
Background Eucommia ulmoides Oliver is a dioecious plant with great economic value, but the underlying metabolite mechanism difference between male and female E. ulmoides remain poorly understood.Results In this study, we integrated a dual-platform metabolomics approach with transcriptomics to systematically analyze differences in metabolite and gene expression in the cortex and leaves of male and female E. ulmoides. As a result, 1,452 metabolites (603 volatile, 849 non-volatile) were characterized, and 156 and 129 differentially accumulated metabolites were identified in FEC vs. MEC and FEF vs. MEF, respectively. The expression of key genes (PLA2G4, DOXs, LOX2S, and CEQORH) involved in alpha-linolenic acid metabolism was significantly altered in MEC. Similarly, the expression of key genes (CHS, FLS, DFR, and ANR) involved in flavonoid biosynthesis was significantly altered in MEF.Conclusion sOur findings shed light on the metabolite mechanism behind the metabolic differences between male and female E. ulmoides and contribute to the exploration of value utilization.
研究领域:
植物学
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分子生物学
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DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-8
·
IF 4.259
Sun Dong,Chen Qi,He Ning,Diao Pan-pan,Jia Li-xing,Duan Shun-shan
Nonylphenol (NP) is a persistent environmental chemical that can disrupt the organism’s endocrine system, and is detected in the surface water and sea. In this study, we investigated whether NP can alter transcriptional expression of sexual differentiation-related genes. Three generations of zebrafish were exposed to 0, 2, 20 and 200 μg·L −1 of NP, and transcriptional expression of sexual differentiation genes were assessed in 10, 20 and 40 dpf in the F1 and F2 generations. Growth of zebrafish exposed to 200 μg·L −1 of NP was inhibited at 125 dpf in the F1 generation. 20 μg·L −1 of NP resulted in 80% females in the F1 generation, but had no effect on the F2 generation. In terms of the sexual differentiation genes, the transcriptional expression of cyp19a1a and esr1 genes were upregulated in 20 μg·L −1 of NP in the F1 generation. But expression of the sexual differentiation genes were not affected in the F2 generation. Overall, NP could affect sexual differentiation and gene transcriptional expression in the F1 generation. The tolerance of contaminant in the offsprings was improved at low concentration.
研究领域:
环境科学
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毒理学
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内分泌学
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水生生物学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Wanqian Peng,Zhiqiang Li,Dingji Cai,Xiaocui Yi,Ji Yue (Jeff) Zhang,Guoyue Zhong,Hui Ouyang,Yulin Feng,Shilin Yang
Background Pinnatifolone A is a typical sesquiterpenoid and the primary active ingredient of Syringa oblata Lindl., has potent anti-inflammatory activity. However, Pinnatifolone A pharmacokinetic and metabolites analysis investigations in male and female rats, as well as its in vitro stability in male and female rat liver microsomes , have not been evaluated and compared. Purpose To investigate preclinical pharmacokinetic and metabolite in both genders, confirm gender differences, and provide usable information for the development of clinical applications. Methods A quick, precise, and sensitive LC-MS/MS method was created and effectively used to determine the pharmacokinetics of oral (140 mg/kg) and intravenous (6.3 mg/kg) Pinnatifolone A in male and female rats, in vitro Pinnatifolone A elimination studies in male and female rat liver microsomes. Following that, a UHPLC-Q-TOF-MS/MS technique was established to identify the metabolic profiles of Pinnatifolone A obtained from rat plasma and excreta. Results In the current study, we established for the first time an LC-MS/MS method for the quantitation of Pinnatifolone A with acceptable linearity and selectivity, recovery and matrix effect, accuracy and precision. The absolute oral bioavailability of Pinnatifolone A was approximately 30.36% in female rats, the clearance (CL) was 20.99±3.33 l/h/kg in female rats and 472.37±437.31 l/h/kg in male rats. This difference in rat genders may pertain to the sex-specific expression of hepatic enzymes as demonstrated in the metabolic stability evaluation in the present research; the male rats exhibited higher CL int(mic) (158.83±9.57 μl/min/mg protein) than female rats (76.47±7.90 μl/min/mg protein) liver microsomes, indicating higher Pinnatifolone A clearance in male rats. Twenty-four metabolites were detected and identified in female and male rats; N-acetylcysteine conjugation metabolite was the most abundant metabolites in both rat feces and urine. Furthermore, male and female rats had significantly different levels of the N-acetylcysteine conjugation metabolite. Hydrogenation metabolite was particular to female rats both in rat fecal and urine. Glucuronide conjugation metabolite was the predominant metabolite in rat plasma, and its amount in female rats was double that of male rats. Conclusions The present research is the first to report the preclinical pharmacokinetics and metabolites of Pinnatifolone A in male and female rats, confirming the gender-based differences. The findings provide a comprehensive overview for further understanding of the pharmacokinetic and metabolic characteristics of Pinnatifolone A and serve as a guide for its future development and utilization.
研究领域:
药理学
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分析化学
·
生物化学
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DOI
PubMed
高影响因子
npj Science of Food
·
2024
·Vol. 8
·期 1
·1-12
·
IF 6.3
Zhang Meng,Du Pengfei,Xiao Yirong,Liu Hao,Wang Meixue,Zhang Yumei,Chen Xin
Sodium dehydroacetate (DHA-Na), a widely used preservative, can induce sex-differentiated coagulation disorders primarily resulting from its metabolism. However, the underlying mechanisms remain poorly understood. Here, we identified several Cytochrome P450 (CYP450) sub-enzymes involved in sex differences related to DHA-Na metabolism, along with two related DHA-Na metabolites. CYP1A2, CYP3A2, and CYP2D1 were primarily responsible for DHA-Na metabolism, which was stronger in male rats than in female rats. Inhibition of these isoforms separately resulted in the DHA-Na metabolic capacity in male rats becoming equal to, or even weaker than, that in female rats. Furthermore, Cyp1a2, Cyp3a2, Cyp2d1 , and Cyp2c11 expression was higher in male rats than in female rats, suggesting these enzymes are related to exhibited sex differences in DHA-Na metabolism. Moreover, 3-glycoloyl-6-methy-2,3-dihydropyran-2,4-dione (C 8 H 8 O 5 ) and 3-imino-6-methyl-2,3-dihydropran-2,4dione (C 6 H 5 O 3 N) were identified as the two main DHA-Na metabolites. These findings provide crucial insights into potential mechanisms underlying sex differences in DHA-Na metabolism and its metabolites in rats.
研究领域:
药理学
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毒理学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
Metabolites
·
2025
·Vol. 15
·期 3
·170
·
IF 3.7
Ningjing Qian,Junyan Jin,Ying Gao,Jiayi Liu,Yaping Wang
Background: Significant sex differences exist in atrial fibrillation (AF). Better understanding of its underlying mechanism would help AF management. This study aimed to investigate the contribution of circulating metabolites to sex differences in AF and the association between them.Methods: A total of 108 patients with AF were enrolled. Untargeted metabolomics were performed in plasma samples of male and female patients. Correlation analysis with clinical characteristics and Mendelian randomization were used to identify sex-specific metabolites associated with AF, which was further validated in additional patients. Transcriptomics data of the left atrium were used to investigate the molecular alteration of the left atrium responding to identified sex-specific circulating metabolites. The effect of selected sex-specific metabolites on cardiomyocytes was further investigated.Results: A total of 60 annotated metabolites were found with different levels between male and female patients. Among these sex-specific metabolites, three metabolites, 7-Methylguanosine, succinic acid, and N-Undecylbenzenesulfonic acid, were positively related to the left atrial remodeling. Additionally, succinic acid was significantly associated with increased risk of AF (OR = 1.26; 95% CI: 1.13 to 1.40;p< 0.001). And, SUCLA2, the gene of succinic acid metabolism, was significantly increased in the left atrium of male patients (fold change = 1.53;p= 0.008). Treatment with succinic acid led to cardiomyocyte hypertrophy and mitochondrial dysfunction.Conclusions: This study highlights sex differences in circulating metabolites in patients with AF and identifies the associations between sex-specific metabolites and AF. succinic acid, which is much higher in male patients, contributes to the process of AF.
研究领域:
心血管病学
·
代谢组学
·
分子生物学
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DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 22
·12260-12268
·
IF 2.936
Meiyu Wu,Liang Chen,Ruiru Li,Mo Dan,Haining Liu,Xinsheng Wang,Xiaochun Wu,Ying Liu,Liming Xu,Liming Xie
Along with the increasing applications of nanomaterials in medical fields, to know the systemic distribution of nanomaterials in the body through a precise method is required for the biosafety assessment of nanomaterials. In this study, we firstly have established a reliable inductively coupled plasma mass spectrometry (ICP-MS) method for concentration measurement of silver (Ag) and gold (Au) in biological tissues. Then, based on this method, the Ag or Au distribution in rat blood and almost all of the organs were analyzed after an i.v. or s.c. administration of Au@Ag NRs. Both the time-dependent contents of Ag and Au in blood and two pharmacokinetic models confirmed the rapid clearance of Ag from blood. At 24 h after i.v. injection, there was the highest level of Ag in liver, followed by portal nodes, spleen, lung, bone marrow and pancreas. In addition, we also found there were gender-related distributions of Ag and Au in some organs, especially after s.c. injection. Therefore, these more comprehensive and important results would give fundamental information for the biological risk assessment of nanomaterials.
研究领域:
医学
·
毒理学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2025
·
IF 6.6
Nana Zhao,Xinxing Xu,Shiyuan Dong,Yuanhui Zhao,Tianhong Liu,Li Liu,Yue Zhao,Mingyong Zeng,Kang Liu
In this study, the flavor quality of male and female mussel meat was investigated by sensory evaluation, gas chromatography-ion mobility spectrometry (GC‒IMS), gas chromatography‒mass spectrometry (GC‒MS) and metabolomics. The sensory evaluation results indicated that the flavor quality of male and female mussel meat was optimal when it was steamed for 8 min and that “fresh” was the most prominent odour attribute. The GC‒IMS and GC‒MS results revealed that aldehydes, ketones and alcohols were the characteristic flavor compounds in male and female mussel meat during different steaming times. Glycerol phospholipid metabolism was the main metabolic enrichment pathway shared by male and female mussel meat, and glycine (Gly), serine (Ser), and threonine (Thr) metabolism were the main metabolic pathways of female mussel meat. Phosphatidylethanolamine, phosphatidylcholine, phosphatidyl-L-serine, phosphatidylglycerol, and 1-acyl-n-glycerin-3-phosphocholine are the precursors of key odour compounds in male and female mussel meat at different steaming times.
研究领域:
食品科学
·
代谢组学
·
海洋生物学
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DOI
高影响因子
CHEMOSPHERE
·
2019
·
IF 5.108
Luyao Zhang,Li Chen,Zhiyuan Meng,Wenjun Zhang,Xin Xu,Zikang Wang,Yinan Qin,Yue Deng,Rui Liu,Zhiqiang Zhou,Jinling Diao
Reptiles, the most diverse taxon of terrestrial vertebrates, might be particularly vulnerable to soil pollution. Reptiles especially lizards have been rarely evaluated in ecotoxicological studies, and there is a very limited report for effects of soil pesticide contaminants on lizards. In this study, male and female lizards ( Eremias argus ) were exposed to Glufosinate-ammonium (GLA) and l - Glufosinate-ammonium (L-GLA) for 60 days. Slower sprint speed, higher frequency of turning back and reduced brain index were observed in treatment groups. The accumulation of GLA in the brain of lizard was higher than that of L-GLA. Moreover, the activities of neurotoxicity-related enzymes and biomarkers of oxidative stress were also investigated. In summary, the neurotoxic effects of lizards have been observed after exposure to GLA and L-GLA. Based on the result of the Integrated Biomarker Response (IBR), males were more sensitive to contaminants than females. On the other hand, the neurotoxic pathways by GLA and L-GLA triggered were slightly different: GLA mainly acted on glutamine synthetase (GS), acetylcholinesterase (AchE) and Catalase (CAT) and L-GLA aimed at AchE, Na + /K + -ATPase, Superoxide dismutase (SOD) and Malondialdehyde (MDA). In summary, the accumulation of GLA and L-GLA in lizard's brain induced neurotoxicity by altering the levels of enzymes related to nervous system and antioxidant activity and further resulted in the decrease of brain index and locomotor performance.
研究领域:
生态毒理学
·
爬行动物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
Metabolites
·
2025
·Vol. 15
·期 2
·106
·
IF 3.7
Yuqing Zhang,Jinhui Zhao,Hui Zhao,Xin Lu,Xueni Jia,Xinjie Zhao,Guowang Xu
Background:Metabolomics serves as a very useful tool for elucidating disease mechanisms and identifying biomarkers. Establishing reference intervals (RIs) of metabolites in a healthy population is crucial to the application of metabolomics in life sciences and clinics.Methods:We enrolled 615 healthy Chinese adults aged between 21 and 85 years. Their health status was ascertained through clinical examinations, biochemical parameters, and medical history. Targeted metabolomics and lipidomics analyses were applied to quantify 705 metabolites and lipids in the serum, establishing RIs and investigating the effect of sex and age on the metabolome and lipidome.Results:This study is the first large-scale effort in China to establish RIs for metabolites in the apparently healthy population. We found that most of the sex-related metabolites, including amino acids, acyl-carnitines and triacylglycerols, had higher concentrations in males, while the other sex-related lipids showed higher concentrations in females. Most of the age-related metabolites increased with age, including those associated with protein synthesis, nitric oxide synthesis, energy metabolism, and lipid metabolism.Conclusions:This study gives the reference intervals of the healthy Chinese metabolome and lipidome and their relationship with sex and age, which facilitates life sciences and precision medicine, especially for disease research and biomarker discovery.
研究领域:
生物化学
·
医学
·
代谢研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）