JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
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2021
·Vol. 329
·期 1
·159-169
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IF 1.371
Zou Qi,Huo Zhuhao,Shao Haiyang,Gu Jianzhong,Xu Gang
The degradation of pyrazinamide (PZA) by electron beam irradiation (EBI) was studied. It was found that the degradation of PZA was efficient with the removal rate of 99% for 0.2 mM PZA under 5 kGy, and the degradation kinetics followed pseudo-first-order kinetics. The presence of CO 3 2− , HCO 3 − , NO 3 − , and fulvic acid inhibited the degradation of PZA. The addition of H 2 O 2 or K 2 S 2 O 8 effectively enhanced the degradation and mineralization of PZA. The scavenger experiments and quantum chemical calculations showed that · OH was the primary reactive species in the degradation. The identification of intermediates and quantum chemical calculations illustrated the mechanism of degradation.
研究领域:
环境科学
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化学工程
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药学
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产品关联
DOI
高影响因子
Journal of Environmental Chemical Engineering
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2025
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IF 7.2
Zeqian Zhang,Hongshan Wu,Qiming Chen,Xiaowei Li,Yimin Cai,Lihua Yuan,Wen Feng
Efficient and selective palladium (Pd) recovery from high-level liquid waste (HLLW) constitutes a crucial task for both precious resource recovery and environmental remediation, but remains challenging to achieve high efficiency, sufficient selectivity, and fast kinetics. Herein, we report a new pyrazinamide ligand (denoted as PA) as the first example of employing pyrazine-based ligand for Pd 2 + separation with impressive efficiency. Using an ionic liquid C 8 mimNTf 2 as diluent, the developed pyrazinamide-ionic liquid (PA-IL) extraction system exhibited attractive merits for Pd 2+ separation such as a wide range of workable acidities from 0.2 M to 5 M HNO 3 , ultra-fast extraction kinetics with equilibrium time of 3 min, and good Pd 2+ selectivity over 16 ions coexisting in simulated HLLW and other non-metallic anions. Slope analysis indicated that the extraction mechanism involves the cation exchange of C 8 mim + and the coextraction of NO 3 - anions in the course of Pd 2+ extraction. Results from a set of spectroscopic investigations and single crystal X-ray diffraction analysis suggest the formation of complexes with stoichiometry of both 1:1 and 2:1 (PA/Pd 2+ ) in solution and in solid state, of which the formation of 2:1 complex is the most thermodynamically favored according to DFT theoretical calculations. This work provides a highly promising pyrazinamide-based extraction system for efficient and selective Pd 2+ separation from HLLW, and brings more understanding about the complexation and coordination behaviors between N-based ligands and Pd 2+ ions.
研究领域:
化学工程
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环境科学
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材料科学
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DOI
高影响因子
TOXICOLOGICAL SCIENCES
·
2016
·Vol. 152
·期 2
·417-428
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IF 3.88
Guo Hong-Li,Hassan Hozeifa M.,Zhang Yun,Dong Si-Zhe,Ding Ping-Ping,Wang Tao,Sun Li-Xin,Zhang Lu-Yong,Jiang Zhen-Zhou
Pyrazinamide (PZA) is an indispensable first-line drug used for the treatment of tuberculosis which may cause serious hepatotoxicity; however, the mechanisms underlying these toxicities are poorly understood. Cholestasis plays an important role in drug-induced liver injury. Since there were no previous published works reported cholestasis and PZA hepatotoxicity relationship, this study aimed to identify whether PZA can induce liver injury with characterized evidences of cholestasis and to clarify expression changes of proteins related to both bile acid synthesis and transport in PZA-induced liver injury. PZA (2 g/kg) was administered for 7 consecutive days by oral gavage. Results showed there were 2-fold elevation in both ALT and AST serum levels in PZA-treated rats. In addition, a 10-fold increment in serum total bile acid was observed after PZA administration. The mRNA and protein expressions of bile acid synthesis and transport parameters were markedly altered, in which FXR, Bsep, Mrp2, Mdr2, Ostα/β, Oatp1a1, Oatp1b2, and Cyp8b1 were decreased (P < .05), while Mrp3, Ntcp, Oatp1a4, and Cyp7a1 were increased (P < .05). Moreover, treatment with the FXR agonist obeticholic acid (OCA) generated obvious reductions in serum ALT, AST, and TBA levels in PZA-treated rats. Those effects were due to transcriptional regulation of pre-mentioned target genes by OCA. Taken together, these results suggested that PZA-induced cholestatic liver injury was related to FXR inhibition, leading to the dysfunction in bile acid synthesis and transport.
研究领域:
药理学
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毒理学
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肝病学
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DOI
PubMed
高影响因子
Expert Opinion on Drug Metabolism & Toxicology
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2020
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IF 3.47
Linsheng Liu,Xianglian Li,Chenrong Huang,Yicong Bian,Xiaoxue Liu,Jun Cao,Wenhao Qu,Liyan Miao
Objectives Rifampin (RIF), isoniazid (INH) and pyrazinamide (PZA) are essential components of the short-term first-line anti-tuberculosis (anti-TB) chemotherapy regimen and can cause hepatotoxicity. However, the mechanism of anti-TB drug-induced hepatotoxicity (ATDH) is currently unclear. We investigate the relevant contributions to liver injury and the pathway of the above-mentioned drugs administered alone or in combination.Methods UPLC-Q-TOF/MS-based metabolomics, bile acids (BAs) analysis and FXR/SHP detection were used to evaluate the toxicity of these drugs and clarify the underlying metabolism-related pathway.Results In C57BL/6 mice administered the corrected clinical doses, RIF, INH and PZA could induced hepatotoxicity; with less toxicity in the combination therapy than RIF. The pathological biochemistry, BAs concentration and metabolically regulated FXR/SHP gene expression analyzes in mice were consistent with the metabolomics results. FXR played a role in the hepatotoxicity of anti-tuberculosis drugs in the obeticholic acid treated and FXR-/- mice. Additionally, the purine and lipid metabolic pathways were involved in ATDH.Conclusion ATDH was involved in bile acids and lipid and purine metabolism. The BAs metabolic pathway involvement in mice was validated in TB patients. The noninvasive metabolomics approach is more systemic than routine toxicity evaluation and can be used to assess compound toxicity and the underlying mechanism.
研究领域:
药理学
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毒理学
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代谢
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肝病学
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传染病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Hehe Bai,Wenjun Gong,Yating Pang,Chaoyang Shi,Zhigang Zhang,Lili Guo,Yafeng Li,Lili Guo,Wenming Wang,Hongfei Wang
Three isomeric nitrosylruthenium complexes [RuNO(Qn)(PZA)Cl] (P1, P2, and P3) with bioactive small molecules 8-hydroxyquinoline (Qn) and pyrazinamide (PZA) as co-ligands were synthesized, and their crystal structures were determined using X-ray diffraction technique. The cellular toxicity of the isomeric complexes was compared to understand the effects of the geometries on the biological activity of the complexes. Both the complexes and the human serum albumin (HSA) complex adducts affected the extent of proliferation of HeLa cells (IC 50 : 0.77–1.45 μM). P2 showed prominent activity-induced cell apoptosis and arrested cell cycles at the G1 phase. The binding constants ( K b ) of the complex with calf thymus DNA (CT-DNA) and HSA were quantitatively evaluated using fluorescence spectroscopy in the range of 0.17–1.56 × 10 4 M −1 and 0.88–3.21 × 10 5 M −1 , respectively. The average binding site (n) number was close to 1. Moreover, the structure of HSA and the P2 complex adduct solved at the resolution of 2.48 Å revealed that one PZA-coordinated nitrosylruthenium complex bound at the subdomain I of HSA via a noncoordinative bond. HSA could serve as a potential nano-delivery system. This study provides a framework for the rational design of metal-based drugs.
研究领域:
无机化学
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生物化学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2020
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IF 7.1
Ying Zhang,Xie-an Yu,Yiting Hu,Xuefei Bai,Ran Zhang,Mi Lu,Jianhui Sun,Jiangwei Tian,Bo-Yang Yu
Cell surface charge serves a significant role in maintaining cell membrane stability and integrity, affecting cell structure/functions and the expression of signaling molecules. With the aggravation of the cell injury, cell surface charge would have a difference, which could be treated as a vital indicator for the discernment of cell pathological states. Herein, we developed a novel and instantaneous response method for the determination of cell viability based on cell surface charge. This study introduced a fluorescence resonance energy transfer-based polydopamine-polyethyleneimine/quantum dot (PDA-PEI/QD) sensor constructed by PDA-PEI with positive charge and QD with negative charge via electrostatic interaction, which can be used to instantaneously read out the cell injured states through fluorescent signal change induced by the comprehensive charged materials on the cell surface. The resulting fluorescence signals induced by different hepatotoxic drugs showed the difference. Furthermore, it was worth noting that the fluorescence change induced by 12 hepatotoxic drugs had a close relationship with cellular states, presenting the consistent tendency with cell viability. Accordingly, this method may have applications in the fields of cell viability detection, drug toxicity evaluation, and even elucidating the mechanism of drug-induced liver injury in the future.
研究领域:
生物传感器
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细胞生物学
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药学
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毒理学
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产品关联
DOI
高影响因子
CRYSTAL GROWTH & DESIGN
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2023
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IF 3.8
Zhiyong Zheng,Yuehua Deng,Weining Xie,Sirui Chen,Xiaoxiao Liang,Shiyuan Liu,Yanbin Jiang,Huaiyu Yang
Multicomponent crystal is an effective way to improve the physicochemical properties of drugs. However, screening for co-formers that form multicomponent crystals with active pharmaceutical ingredients is still a challenge. In this study, a co-former prediction method based on partial least squares (PLS) regression was developed. First, 101 positive and negative samples reported were traced from the literature as a training set, based on which seven prediction models were built. Ciprofloxacin (CIP) was selected as the model drug, and the prediction models developed were adopted to predict co-formers which might form multicomponent crystals with CIP. Seven CIP multicomponent crystal systems were successfully prepared experimentally, six of which were hit by the two-parameter prediction model with the Hansen solubility parameter and the conductor-like screening model for real solvents, which achieved an overall accuracy and positive accuracy of 85 and 75%, respectively, higher than those of other models. All seven multicomponent crystal systems showed an increase in process solubility in pH 6.8 phosphate buffer solution (1.06–3.92-fold) and exhibited two different types of dissolution behaviors, wherein three samples exhibited a supersaturated peak in the dissolution process, while the other four did not. This difference was mainly due to the different rates of CIP trihydrate precipitation. The hygroscopic stability of all multicomponent crystals at room temperature and 95% relative humidity was substantially improved compared to raw CIP. This study provides a simple and effective strategy for the predictive screening of multicomponent crystal systems.
研究领域:
药学
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材料科学
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化学
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产品关联
DOI
高影响因子
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