&lt;p&gt;Loxoprofen Sodium Alleviates Oxidative Stress and Apoptosis Induced by Angiotensin II in Human Umbilical Vein Endothelial Cells (HUVECs)&lt;/p&gt;

Ji, Chuanzhao; Yu, Yang; Zhang, Min; Yu, Wenyan; Dong, Shuang

doi:10.2147/dddt.s266175

Cited by 10 publications

(4 citation statements)

References 41 publications

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“…A lot of literature reports that AT2R is one of the functional receptors of Angiotensin II, which has been proven to mediate the progress of apoptosis. [8] In our current study, the inhibitory effect of p53 was stronger than that of AT1R, indicating that AT2R may also be involved in this process.…”

Section: Discussionsupporting

confidence: 46%

“…The optical density of the plate was read using an ELISA reader, and the concentration of the test sample was calculated. [8] 2.3 Determination of Arachidonic acid 12-lipoxygenase, Vascular endothelial growth factor ,p53,P21 After treatment with the corresponding drugs, HUVECs were lysed in RIPA buffer containing a mixture of protease inhibitors and centrifuged to extract total protein. Protein concentrations were determined using a BCA protein assay kit according to the manufacturer's instructions, and 25 µg of protein was analyzed by 8% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).…”

Section: Measurement Of Glutathione and Malonaldehydementioning

confidence: 99%

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The Study on Angiotensin II Induced-Ferroptosis in Vascular Endothelial Cells

Fang

liu

Cavdar

et al. 2021

Preprint

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PurposeTo verify the effect of Angiotensin II on ferroptosis in vascular endothelial cells and clarify the related mechanism. MethodsHUVECs were evaluated for p53, P21,ALOX12, VEGF, MDA,GSH. Molecular marker impact upon AngII-induced ferroptosis was evaluated with students’ t-test，one-way analysis of variance (ANOVA).ResultsAs the concentration of Ang II increased，the level of ALOX12, P53,GSH and MDA increased in HUVECs. The expression of VEGFA in HUVECs is negatively correlated with dose of Ang II. Incubation of HUVECs in AngII and valsartan for 48hr reduces ALOX12, P21, GSH and MDA. Compared with the single AngII group, ALOX12, P21, GSH and MDA in valsartan group was decreased significantly（p=0.000）.In pifithrin-α hydrobromide-treated, ALOX12, P21, GSH and MDA was reduced significantly, as compared to valsartan group（p=0.000）. The most larger reduction in ALOX12, P21,GSH and MDA was pifithrin - α hydrobromide combined with valsartan group. In contrast, the expression of VEGFA increased significantly after HUVECs were treated with pifithrin - α hydrobromide and valsartan（p=0.000）.ConclusionsAngII can induce ferroptosis of vascular endothelial cells in a dose-dependent manner. The mechanism of AngII-induced ferroptosis may be regulated through the signal axis of ATR1,2-p53-ALOX12.

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Section: Discussionsupporting

confidence: 46%

Section: Measurement Of Glutathione and Malonaldehydementioning

confidence: 99%

The Study on Angiotensin II Induced-Ferroptosis in Vascular Endothelial Cells

Fang

liu

Cavdar

et al. 2021

Preprint

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“…Loxoprofen is metabolized by cytochrome P450 (CYP3A4 and CYP3A5) and UDP‐glucuronosyltransferase (UGT) enzymes in the liver (van den Anker, Reed, Allegaert, & Kearns, 2018). Studies have shown that the carboxylic acid moiety contained in the structure of loxoprofen was associated with idiosyncratic drug toxicity, mainly due to the liver injury caused by the formation of the loxoprofen and loxoprofen tromethamine metabolite acyl glucuronide by the enzyme UGT2B7 (Amagase et al, 2012; Ji, Yu, Zhang, Yu, & Dong, 2020). However, how loxoprofen tromethamine causes embryo‐fetal toxicity is still unknown and warrants further research.…”

Section: Discussionmentioning

confidence: 99%

Embryo‐fetal developmental toxicity and toxicokinetics of loxoprofen tromethamine intravenously administered to pregnant rats

Peng¹,

Zhao

Liu³

et al. 2022

Birth Defects Research

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Background: Loxoprofen tromethamine is a novel structural compound related to loxoprofen. It has been used for the treatment of pain and inflammation. However, the embryo-fetal developmental toxicity (EFDT) of loxoprofen tromethamine has not been evaluated in detail in vivo. This study investigated the EFDT and toxicokinetics of loxoprofen tromethamine in rats. Methods: The aim of this study was to investigate the potential reproductive toxicity on embryo-fetal development of loxoprofen tromethamine (0, 1, 3, and 10 mg/kg/day) and sodium cyclophosphamide (CP) (2.8 mg/kg/day) administered by intravenous injection to pregnant rats during gestation days (GDs) 6-15. Pregnant rats were euthanized on GD20. The numbers of live/dead fetuses, resorptions, implantations, and corpora lutea, gravid uterus mass, placenta mass, fetal gender ratios, body weight, and skeletal development were evaluated. In a concomitant toxicokinetic (TK) study (10 pregnant rats per group), plasma TK parameters and the tissue distribution of loxoprofen tromethamine were tested. Results: On GD20, rats were anesthetized and dissected by caesarean section.The appearance, internal organs, gravid uterus weight, embryo implantation number, and implantation loss rate in maternal rats of each group did not reveal any lesions. In fetuses, there were no significant differences in the fetus weight, embryo resorption number, stillbirth number, or fetal visceral examination in all test groups compared to the negative control group. However, in the high-dose group, the fetuses showed significant differences in the anomalies of the bones compared to the negative control group. The TK study showed that in the dose range of 1-10 mg/kg, the C max and AUC (0-t) of loxoprofen tromethamine in animals after the first administration increased proportionally to the dose, showing linear kinetic characteristics; after the last administration, the C max and AUC (0-t) increased disproportionately to the dose, showing nonlinear kinetic characteristics. The results of tissue distribution show that

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“…Solubility can be defined as the capability of a solute to be dissolved in a particular solvent to obtain a homogenous Loxoprofen sodium is known as an important nonsteroidal anti-inflammatory drug (NSAID), which has considerable analgesic influence (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) times greater than ketoprofen or naproxen) that made it an appropriate anti-inflammatory and antipyretic agent [4]. Additionally, this drug has shown its great potential of application to relieve the acute/chronic pain without having serious side effects for the gastrointestinal tract [5,6]. Loxoprofen is instantly metabolized through the trans-alcohol formation, acts as a non-selective inhibitor of cyclooxygenase after oral administration, and reaches its maximum plasma concentration in less than 1 h [7].…”

Section: Introductionmentioning

confidence: 99%

Solubility Optimization of Loxoprofen as a Nonsteroidal Anti-Inflammatory Drug: Statistical Modeling and Optimization

et al. 2022

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Industrial-based application of supercritical CO2 (SCCO2) has emerged as a promising technology in numerous scientific fields due to offering brilliant advantages, such as simplicity of application, eco-friendliness, and high performance. Loxoprofen sodium (chemical formula C15H18O3) is known as an efficient nonsteroidal anti-inflammatory drug (NSAID), which has been long propounded as an effective alleviator for various painful disorders like musculoskeletal conditions. Although experimental research plays an important role in obtaining drug solubility in SCCO2, the emergence of operational disadvantages such as high cost and long-time process duration has motivated the researchers to develop mathematical models based on artificial intelligence (AI) to predict this important parameter. Three distinct models have been used on the data in this work, all of which were based on decision trees: K-nearest neighbors (KNN), NU support vector machine (NU-SVR), and Gaussian process regression (GPR). The data set has two input characteristics, P (pressure) and T (temperature), and a single output, Y = solubility. After implementing and fine-tuning to the hyperparameters of these ensemble models, their performance has been evaluated using a variety of measures. The R-squared scores of all three models are greater than 0.9, however, the RMSE error rates are 1.879 × 10−4, 7.814 × 10−5, and 1.664 × 10−4 for the KNN, NU-SVR, and GPR models, respectively. MAE metrics of 1.116 × 10−4, 6.197 × 10−5, and 8.777 × 10−5errors were also discovered for the KNN, NU-SVR, and GPR models, respectively. A study was also carried out to determine the best quantity of solubility, which can be referred to as the (x1 = 40.0, x2 = 338.0, Y = 1.27 × 10−3) vector.

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<p>Loxoprofen Sodium Alleviates Oxidative Stress and Apoptosis Induced by Angiotensin II in Human Umbilical Vein Endothelial Cells (HUVECs)</p>

Cited by 10 publications

References 41 publications

The Study on Angiotensin II Induced-Ferroptosis in Vascular Endothelial Cells

The Study on Angiotensin II Induced-Ferroptosis in Vascular Endothelial Cells

Embryo‐fetal developmental toxicity and toxicokinetics of loxoprofen tromethamine intravenously administered to pregnant rats

Solubility Optimization of Loxoprofen as a Nonsteroidal Anti-Inflammatory Drug: Statistical Modeling and Optimization

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