A5101624212- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Inflammatory mediators and NSAID effects
- Drug-Induced Hepatotoxicity and Protection
- Eicosanoids and Hypertension Pharmacology
- Estrogen and related hormone effects
- Hormonal Regulation and Hypertension
- HIV/AIDS drug development and treatment
- Pharmacological Effects and Toxicity Studies
- Biofuel production and bioconversion
- Analytical Chemistry and Chromatography
- Neonatal Respiratory Health Research
- Receptor Mechanisms and Signaling
- Computational Drug Discovery Methods
- Lignin and Wood Chemistry
- Electrolyte and hormonal disorders
- Blood Pressure and Hypertension Studies
- Immune cells in cancer
- Bioactive Compounds and Antitumor Agents
- Synthesis and Reactions of Organic Compounds
- Cardiovascular Health and Disease Prevention
- Catalysis for Biomass Conversion
- Regulation of Appetite and Obesity
- Peroxisome Proliferator-Activated Receptors
- Colorectal Cancer Screening and Detection
Changzhou University
2020-2025
Nanjing Medical University
2013-2025
Jinan University
2025
Hunan University
2025
Zhongda Hospital Southeast University
2025
Shanghai Institute of Materia Medica
2025
University of Chinese Academy of Sciences
2025
Nanjing University of Chinese Medicine
2025
Chengdu Women's and Children's Central Hospital
2021-2024
University of Electronic Science and Technology of China
2021-2024
Therapy with the oral antidiabetic agent troglitazone (Rezulin) has been associated cases of severe hepatotoxicity and drug-induced liver failure, which led to recent withdrawal product from U.S. market. While mechanism this toxicity remains unknown, it is possible that chemically reactive metabolites drug play a causative role. In an effort address possibility, study was undertaken determine whether undergoes metabolism in human microsomal preparations electrophilic intermediates. Following...
The nonsteroidal anti-inflammatory drug diclofenac causes a rare but potentially fatal hepatotoxicity that may be associated with the formation of reactive metabolites. In this study, three glutathione (GSH) adducts, namely 5-hydroxy-4-(glutathion-S-yl)diclofenac (M1), 4'-hydroxy-3'-(glutathion-S-yl)diclofenac (M2), and 5-hydroxy-6-(glutathion-S-yl)diclofenac (M3), were identified by liquid chromatography-tandem mass spectrometry analysis bile from Sprague-Dawley rats injected i.p. single...
Raloxifene is a selective estrogen receptor modulator which effective in the treatment of osteoporosis postmenopausal women. We report herein that cytochrome P450 (P450)3A4 inhibited by raloxifene human liver microsomal incubations. The nature inhibition was irreversible and NADPH- preincubation time-dependent, with K(I) k(inact) values estimated at 9.9 microM 0.16 min(-1), respectively. observed loss 3A4 activity attenuated partially glutathione (GSH), implying involvement reactive...
Recently, it was shown that diclofenac metabolized in rats to reactive benzoquinone imines via cytochrome P450-catalyzed oxidation. These metabolites also were detected human hepatocyte cultures the form of glutathione (GSH) adducts. This report describes results further studies aimed at characterizing hepatic P450-mediated bioactivation diclofenac. The formed vitro trapped by GSH and analyzed LC/MS/MS. Thus, three adducts, namely, 5-hydroxy-4-(glutathion-S-yl)diclofenac (M1),...
Recent studies have demonstrated that the pregnane X receptor (PXR) is a key regulator of cytochromes P450 3A (e.g. CYP3A4 in human) gene expression. As result, activation PXR may lead to protein over-expression. Because induction could result clinically important drug interactions, there has been great interest reducing possibility by candidates drug-discovery programmes. In order provide structural insight for attenuating candidate-mediated activation, we used docking approach study...
The cytochrome P-450 (CYP)3A4-mediated metabolism of diclofenac is stimulated in vitro by quinidine. A similar effect observed incubations with monkey liver microsomes. We describe an vivo interaction and quinidine that leads to enhanced clearance monkeys. After a dose via portal vein infusion at 0.055 mg/kg/h, steady-state systemic plasma drug concentrations three male rhesus monkeys were 87, 104, 32 ng/ml, respectively (control). When was coadministered (0.25 mg/kg/h) the same route,...
The metabolism of diclofenac to its 5-hydroxylated derivative in humans is catalyzed by cytochrome P450 (CYP)3A4. We report herein that vitro this biotransformation pathway stimulated quinidine. When was incubated with human liver microsomes the presence quinidine, formation 5-hydroxydiclofenac increased approximately 6-fold relative controls. Similar phenomena were observed diastereoisomers including quinine and threo epimers, which produced an enhancement order 6- 9-fold. This stimulation...
Estrogens and selective estrogen receptor modulators (SERMs) are prescribed widely in the clinic to alleviate symptoms postmenopausal women, they metabolized reactive intermediates, which may elicit adverse effects. As part of our efforts develop safer SERMs, vitro covalent protein binding (2S,3R)-(+)-3-(4-hydroxyphenyl)-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2,3-dihydro-1,4-benzoxathiin-6-ol (I) was evaluated. Radioactivity from [3H]I became covalently bound proteins a fashion that both time-...