BIOMEDICAL CHROMATOGRAPHY
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2019
·Vol. 33
·期 9
·e4568
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IF 1.748
Liping Zhou,Hexiang Liu,Zhongyong Xu,Su Guan,Lei Zhang
Febuxostat is a novel nonpurine type of highly selective xanthine oxidoreductase inhibitor. A rapid and sensitive ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry method for simultaneous separation and determination of febuxostat and its metabolites in rat serum and urine was developed at various time points after oral administration to the rats. The febuxostat metabolites were predicted by biotransformation software and transformed to a personal compound database to quickly determine the possible metabolites from the MS1 data. The possibility of the MS/MS fragmentation was calculated by the Molecular Structure Correlator software. As a result, five phase I and two phase II metabolites in rat serum, and seven phase I and three phase II metabolites in rat urine were identified, of which four metabolites (M2, M5, M6, M7) have not been reported before. The metabolite toxicities are predicted, and the results are helpful for the design of new xanthine oxidoreductase inhibitors.
研究领域:
药理学
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分析化学
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毒理学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Xingyu Gao,Zixia Hu,Yang Wang,Guode Zhao,Yan Shen,Hao Zhou,Yufen Liao,Weiwei Li,Ying Peng,Jiang Zheng
Gramine (GRM), which occurs in Gramineae plants, has been developed to be a biological insecticide. Exposure to GRM was reported to induce elevations of serum ALT and AST in rats, but the mechanisms of the observed hepatotoxicity have not been elucidated. The present study aimed to identify reactive metabolites that potentially participate in the toxicity. In rat liver microsomal incubations fortified with glutathione or N-acetylcysteine, one oxidative metabolite (M1), one glutathione conjugate (M2), and one N-acetylcysteine conjugate (M3) were detected after exposure to GRM. The corresponding conjugates were detected in the bile and urine of rats after GRM administration. CYP3A was the main enzyme mediating the metabolic activation of GRM. The detected GSH and NAC conjugates suggest that GRM was metabolized to a quinone imine intermediate. Both GRM and M1 showed significant toxicity to rat primary hepatocytes.
研究领域:
毒理学
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药理学
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生物化学
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DOI
PubMed
高影响因子
INTERNATIONAL ENDODONTIC JOURNAL
·
2019
·Vol. 53
·期 1
·72-83
·
IF 3.331
T. Ning,J. Shao,X. Zhang,X. Luo,X. Huang,H. Wu,S. Xu,B. Wu,D. Ma
Aim To comparatively evaluate changes in the proliferation and mineralization abilities of dental pulp stem cells (DPSCs) from juvenile and adult rats in a lipopolysaccharide (LPS)-induced inflammatory microenvironment to provide a theoretical basis for the age-related differences observed in DPSCs during repair of inflammatory injuries. Methodology DPSCs were isolated from juvenile (JDPSCs) and adult rats (ADPSCs), and senescence-associated β-galactosidase staining was used to compare senescence between JDPSCs and ADPSCs. Effects of LPS on JDPSCs and ADPSCs proliferation were investigated by cell counting kit-8 assays and flow cytometry. Alizarin red staining, quantitative reverse transcription polymerase chain reaction and Western blot assay were used to examine the effects of LPS on mineralization-related genes and proteins in JDPSCs and ADPSCs. Immunohistochemistry was used to compare interleukin-1β (IL-1β) and osteocalcin (OCN) expression in the pulpitis model. Unpaired Student's t -tests and one-way anova were used for statistical analysis. Results DPSCs were isolated from juvenile and adult rat dental pulp tissues. At low concentrations (0.1–1 μg mL −1 ), LPS significantly promoted the proliferation of JDPSCs ( P < 0.01) and ADPSCs ( P < 0.01 or P < 0.05), with the effect being stronger in JDPSCs than in ADPSCs. In addition, mineralized nodules and the expression of mineralization-related genes ( OCN , DSPP , ALP , BSP ) increased significantly after stimulation with LPS (0.5 μg mL −1 ) in JDPSCs and ADPSCs ( P < 0.01 or P < 0.05), and JDPSCs displayed a more obvious increase than ADPSCs. Western blots revealed OCN and ALP expression levels in JDPSCs treated with LPS were significantly upregulated ( P < 0.05); meanwhile, ALP expression in ADPSCs increased slightly but significantly ( P < 0.05), and OCN expression was not affected. Finally, IL-1β expression was significantly higher ( P < 0.05) and OCN expression was significantly lower ( P < 0.05) in the inflamed dental pulp of adult rats than in juvenile rats. Conclusions A certain degree of inflammatory stimulation promoted the proliferation and mineralization of DPSCs; however, this effect declined with age. The DPSCs of adult donors in an inflammatory microenvironment have a weaker repair ability than that of juvenile donors, who are better candidates for tissues damage repair.
研究领域:
牙科学
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干细胞生物学
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炎症
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细胞老化
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DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2023
·
IF 6
Xucong Huang,Zhenghua Wu,Yanchao Liu,Mengqi Jia,Wenjuan Zhao,Shuowen Wang,Xinhui Jiang,Yuefen Lou,Guorong Fan
A simple, sensitive, and rapid LC-MS/MS method for the simultaneous determination of BIC, the M7 and M8 active metabolites in SD rat plasma was developed. After salting-out assisted liquid–liquid extraction (SALLE) with 5 M ammonium acetate solution, the sample was analyzed on a Sciences column (C18 3.0 × 100 mm, 3 μm) using a gradient elution at 40 ℃ within 7 min. The assay displayed excellent linearity in the range of 4–2000 ng/mL for M7 and BIC, and 1–500 ng/mL for M8. The results of this method exhibited that the precision, accuracy, matrix effect, recovery, and stability of BIC, M7 and M8 met all requirements for the quantitation in plasma samples. The pharmacokinetic result showed that the AUC (0→t) was calculated as 383.1 ± 164.4 (ng/mL·h) for BIC, and 5627 ± 1261 (ng/mL·h) for M7 after oral administration with BIC. Compared with BIC group, the pharmacokinetic parameters in BIC-NPs group were improved. Augmentation in AUC (0→t) (3.02-fold) and t 1/2 (1.43-fold) for BIC. Meanwhile, double peak phenomenon was observed on the mean plasma concentration–time curves of M7 in BIC and BIC-NPs group. In conclusion, both BIC and BIC-NPs were metabolized to abundant M7 in SD rat, which would provide a basis for researching the treatment mechanism of liver injury.
研究领域:
药物代谢
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药理学
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分析化学
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DOI
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2022
·
IF 3.571
Yun Li,Dan Zhang,Yan Mo,Teng Zeng,Tongzhi Wu,Lingqiao Liu,Hua Zhang,Chang Chen
Endogenous steroids, including sex hormones and bile acids , are a group of essential compounds with various biological functions. In this study, we developed an LC-MS method that simultaneously measures 14 sex hormones and metabolites (SH) and 32 bile acids (BA) in rat plasma. Multiple innovative approaches were applied to increase the sensitivity and specificity, including optimization of the mobile phases , gradients, and dynamic multiple reaction monitoring (DMRM) transitions. The method was validated and applied on plasma samples from pregnant rats before and 0.5 h after oral glucose tolerance test (OGTT) at gestational days 0.5 and 18.5. Results showed that the method was applicable, and 9 SH and 30 BA were measurable in the samples. In summary, this method is applicable in studies on SH and BA in rat plasma, and may also be used on other matrix and species.
研究领域:
分析化学
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药理学
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内分泌学
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DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2025
·
IF 3.1
Huang Lulu,Ning Chen,He Jiake,Wang Mingcheng,Chen Xijing,Guo Xiaohui,Zhong Lin
Multimorbidity, therapeutic complexity, and polypharmacy, which greatly increases the risk of drug-drug interactions (DDIs) and adverse medical outcomes, have become important and growing challenges in clinical practice. Statins are frequently prescribed to manage post-transplant dyslipidemia and reduce overall cardiovascular risk in solid organ transplant recipients. This study aimed to determine whether rosuvastatin has significant DDIs with tacrolimus (the first-line immunosuppressant) and to evaluate the risk of hepatotoxicity associated with concomitant therapy. We first studied whether a rat model could be established to assess the magnitude of rosuvastatin-tacrolimus DDI. The liver function index and histopathological examination were performed to investigate the characteristics of hepatotoxicity in the presence and absence of DDI. The clinical DDI potential between rosuvastatin and tacrolimus was also explored. Single-dose intravenous administration of tacrolimus did not significantly affect the area under the plasma concentration–time curve (AUC 0-∞ ), clearance (CL), and volume of distribution at steady-state ( V ss ) of rosuvastatin in rats, despite a 96.7% increase in the rosuvastatin maximum plasma concentration ( P = 0.024). Multiple doses of intravenous tacrolimus had no effect on the systemic disposition of rosuvastatin, but significantly increased aspartate transaminase (AST) by 42.6% ( P = 0.043). Multiple doses of intravenous tacrolimus and rosuvastatin significantly altered the disposition of rosuvastatin, reducing alanine aminotransferase (ALT) and AST by 38.3% ( P = 0.040) and 31.6% ( P = 0.019), respectively. Histological evaluation of the liver specimens revealed patterns of drug-induced liver injury in rats. At clinically relevant doses, tacrolimus was predicted to be unable to cause pharmacokinetic interactions with rosuvastatin through basic models. The concomitant administration of tacrolimus and rosuvastatin has a minor impact on rosuvastatin pharmacokinetics; however, mild hepatotoxicity has been observed in rats.
研究领域:
药理学
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毒理学
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临床医学
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
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2021
·
IF 3.503
Cai-Yun Zhang,Ya-Ting Lu,Yin-Feng Tan,Qi-Bing Liu,Lin Dong,Ning Ma,Wei-Ying Lu,Zhi-Heng Su,Xiao-Po Zhang
Context Tadehaginoside, an active ingredient isolated from Tadehagi triquetrum (Linn.) Ohashi (Leguminosae), exhibited various biological activities. However, the pharmacokinetics and tissue distribution which affect tadehaginoside’s therapeutic actions and application remain elusive.Objective To clarify the metabolism of tadehaginoside in vivo.Materials and methods The pharmacokinetics and tissue distribution of tadehaginoside and its metabolite p-hydroxycinnamic acid (HYD) were investigated using LC-MS/MS. Pharmacokinetic parameters were determined in 10 Sprague-Dawley rats divided into two groups, the intravenous group (5 mg/kg) and the oral group (25 mg/kg). For the tissue-distribution study, 20 rats were intravenously given tadehaginoside (5 mg/kg) before the experiment (n = 4). Biological samples were collected before drug administration (control group) and after drug administration.Results The linearity, accuracy, precision, stability, recovery and matrix effect of the method were well-validated and the results satisfied the requirements of biological sample measurement. Treatment with tadehaginoside via intragastric and intravenous administration, the calculated Cmax in rats was 6.01 ± 2.14 ng/mL and 109.77 ± 4.29 ng/mL, and Tmax was 0.025 ± 0.08 h and 0.08 h, respectively. The results indicated that the quick absorption of tadehaginoside was observed following intravenous administration, and tadehaginoside in plasma of rats with intragastric administration showed relatively low concentration may be due to the formation of its metabolite. Tissue-distribution study indicated that kidney and spleen were the major distribution organs for tadehaginoside in rats and there was no long-term accumulation in most tissues.Discussion and conclusion These results could provide clues for exploring the bioactivity of tadehaginoside based on its pharmacokinetic characteristics.
研究领域:
药理学
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分析化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL DAIRY JOURNAL
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2013
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IF 2.333
C.F. Guo,J.Y. Li
Elevated serum cholesterol is a major risk factor for coronary artery disease. Probiotics may manage elevated cholesterol. The hypocholesterolaemic effects of Lactobacillus casei F0822 and its functional mechanisms were investigated in rats . The serum total cholesterol, low-density lipoprotein cholesterol and liver total cholesterol levels significantly decreased in rats fed a high-cholesterol diet plus drinking water supplemented with viable cells of strain F0822; however, there was no significant difference in the serum high-density lipoprotein cholesterol levels among the treatment groups. The hypocholesterolaemic mechanisms of strain F0822 were attributed to its ability to suppress the reabsorption of bile acids into the enterohepatic circulation though hydrolysis of conjugated bile acids in the small intestine, binding of deoxycholic acid and hyodeoxycholic acid in the large intestine, and increase in propionate:acetate ratio in the large intestine in rats. Strain F0822 may be a promising probiotic culture with potential hypocholesterolaemic action in human.
研究领域:
营养学
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医学
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微生物学
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产品关联
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2014
·
IF 2.694
Wei-min Zhang,Rui-fang Li,Ming Sun,Da-ming Hu,Jian-fei Qiu,Yun-hao Yan
A rapid, sensitive and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) was developed and validated for the determination and pharmacokinetic investigation of avicularin in rat plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2 mL of acetonitrile–methanol (9:1, v/v) to a 0.1 mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile–0.1% formic acid in water with gradient elution. The total run time was 1.60 min and the elution of avicularin was at 1.20 min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring (MRM) mode using the respective transitions m / z 434.1 → 301.3 for avicularin and m / z 237.2 → 194.3 for carbamazepine (IS), respectively. The calibration curve was linear over the range of 10–3000 ng/mL with a lower limit of quantitation (LLOQ) of 10 ng/mL. Mean recovery of avicularin in plasma was in the range of 84.2–89.5%. Intra-day and inter-day precision were both <12%. This method was successfully applied in pharmacokinetic study after intravenous administration of 5.0 mg/kg avicularin in rats.
研究领域:
分析化学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
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2022
·
IF 5.011
Zhicheng Duan,Tingting Yang,Lin Li,Xue Wang,Chujing Wei,Ziyin Xia,Yuanyuan Chai,Xin Huang,Luyong Zhang,Zhenzhou Jiang
Bile acids (BAs) were selected as biomarkers for the diagnosis and prevention of multiple liver diseases, and they were also considered as an important signal transductor via “liver-gut” axis. As important factors for maintaining the normal function and tissue morphology, BA homeostasis throughout the enterohepatic circulation system was guaranteed by BA synthases and transporters, nuclear receptors (NRs) and gut microbiota , all of which presented significant species differences. Thus, we simultaneously quantify BA profiles in the enterohepatic circulation of SD rats and C57BL/6 mice to reveal the species differences of BA homeostasis between these two main rodents of preclinical studies . Our results showed that BA profiles of mice plasma, bile and liver were most dissimilar from these of rats. Meanwhile, BAs profiles also presented obvious species differences in the intestine of mice and rats, especially small intestine . Unlike rats, taurine-conjugated bile acids (T-BAs) were predominant in mice small intestine content and tissue, in which taurocholic acid (TCA) was the most prominent BAs. BAs dynamic analysis showed that compared with rats, mice showed stranger taurine and glycine de-conjugations in lager intestine. However, both the ratios of unconjugated bile acids (Un-BAs) to conjugated BAs, and secondary BAs to primary BAs in mice small content and tissue were all much lower than these in rats. Furthermore, ileum BAs profiles also showed significantly separation trend between rats and mice, whether content or tissue. Our data revealed that the patterns of BAs homeostasis in mice enterohepatic circulation system were significantly different from these in rats (especially in intestine), suggesting that more cautious should be paid to the selection of BAs as biomarkers for disease diagnosis or/and drug induced toxicity, and the certain role and mechanism of individual BA in the pathological process of BA-related diseases via “liver-gut” axis should be verified by using of multiple species.
研究领域:
生物学
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医学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2018
·Vol. 9
·期 9
·4858-4864
·
IF 3.289
Bo Chen,Jie Zhou,Qilu Meng,Yang Zhang,Shihua Zhang,Liang Zhang
Tea polyphenols (TP) have many health benefits, but most are metabolized into low molecular-weight phenolic acids after oral administration. In the present study, the absorption, metabolism, and excretion of catechins in rats fed a normal chow diet and in obese rats fed a high-fat and high-sugar (HFHS) diet were compared. After a ten-day oral administration of TP (500 mg per kg bw), the plasma levels of (−)-epigallocatechin gallate (EGCG) and (−)-gallocatechin gallate (GCG) in obese rats were significantly lower than those in the normal group. In obese rats, the fecal levels of EGCG, (−)-epicatechin gallate (ECG) and GCG were significantly enhanced. Ten phenolic metabolites of TP were quantitatively analyzed, and the results showed that 4-hydroxyphenylacetic acid was the primary metabolite in feces and plasma. The plasma and fecal concentrations of 4-hydroxyphenylacetic acid in the obese group were significantly lower than those in normal rats, but the levels of 4-hydroxyphenylpropionic acid in plasma and feces were increased. The content of other phenolic acids was also dramatically changed. These results suggested that a HFHS diet might influence the excretion of tea catechins, leading to insufficient metabolism of catechins by the gut microflora.
研究领域:
营养学
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药理学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 17
·3117
·
IF 3.06
Mengqi Zhang,Xia Ren,Shijun Yue,Qing Zhao,Changlun Shao,Changyun Wang
Acanthus ilicifolius herb (AIH), the dry plant ofAcanthus ilicifoliusL., has long been used as a folk medicine for treating acute and chronic hepatitis. Phenylethanoid glycosides (PhGs) are one family of the main components in AIH with hepatoprotective, antioxidant, and anti-inflammatory activities. In this study, the pharmacokinetics of AIH was investigated preliminarily by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS). A simultaneously quantitative determination method for four PhGs (acteoside, isoacteoside, martynoside, and crenatoside) in rat plasma was first established by UPLC-MS/MS. These four PhGs were separated with an ACQUITY UPLC BEH C18column (2.1 × 50 mm, 1.7 μm) by gradient elution (mobile phase: MeCN and 0.1% formic acid in water, 0.4 mL/min). The mass spectrometry detection was performed using negative electrospray ionization (ESI−) in multiple reaction monitoring (MRM) mode. By the established method, the preliminary pharmacokinetics of AIH was elucidated using the kinetic parameters of the four PhGs in rat plasma after intragastric administration of AIH ethanol extract. All four PhGs showed double peaks on concentration-time curves, approximately at 0.5 h and 6 h, respectively. Their elimination half-lives (t1/2) were different, ranging from 3.42 h to 8.99 h, although they shared similar molecular structures. This work may provide a basis for the elucidation of the pharmacokinetic characteristics of bioactive components from AIH.
研究领域:
药理学
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分析化学
✓ 已验证
DOI
高影响因子
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