Protective effects of tiopronin on oxidatively challenged human lung carcinoma cells (A549)

Beltz, Justin; Chernatynskaya, Anna; Pfaff, Annalise; Erçal, Nuran

doi:10.1080/10715762.2020.1763332

Cited by 10 publications

(8 citation statements)

References 41 publications

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“…Different concentrations (0.5 mM and 1 mM) of t BHP were applied. After a 2 h treatment, the GSH levels were decreased significantly in both treatment groups ( p < 0.05 and p < 0.001, Figure 4 and Figure S2 ), consistent with our previous results obtained using HPLC with fluorescence detection [ 26 ]. The decrease in GSSG levels may be attributed to the conversion of GSSG to GSH with the upregulation of the GSH recycling pathway under oxidative stress [ 4 , 35 ].…”

Section: Resultssupporting

confidence: 91%

“…As shown in Figure 3 and Table S1 , the resulting profiles from each cell line differed substantially from each other. We observed that the GSH level of A549 cells in this study was similar to that obtained in our previous study [ 26 ], in which NEM derivatization was not performed, indicating that the derivatization step likely has little or no effect on the protein quantification. Principal component analysis revealed distinct clusters of profiles obtained from the same cell line ( Figure S1 ).…”

Section: Resultssupporting

confidence: 86%

“…t BHP was used to induce oxidative stress in vitro. t BHP solutions were freshly prepared from concentrated stock solutions immediately prior to each experiment [ 26 ]. For all experiments, the cells were seeded at 1 × 10 6 cells per well on a six-well plate incubated in complete medium overnight prior to the experimental treatment.…”

Section: Methodsmentioning

confidence: 99%

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Extensive Thiol Profiling for Assessment of Intracellular Redox Status in Cultured Cells by HPLC-MS/MS

Chernatynskaya

Pfaff

et al. 2021

Antioxidants

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Oxidative stress may contribute to the pathology of many diseases, and endogenous thiols, especially glutathione (GSH) and its metabolites, play essential roles in the maintenance of normal redox status. Understanding how these metabolites change in response to oxidative insult can provide key insights into potential methods of prevention and treatment. Most existing methodologies focus only on the GSH/GSH disulfide (GSSG) redox couple, but GSH regulation is highly complex and depends on several pathways with multiple redox-active sulfur-containing species. In order to more fully characterize thiol redox status in response to oxidative insult, a high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method was developed to simultaneously determine seven sulfur-containing metabolites, generating a panel that systematically examines several pathways involved in thiol metabolism and oxidative stress responses. The sensitivity (LOQ as low as 0.01 ng/mL), accuracy (88–126% spike recovery), and precision (≤12% RSD) were comparable or superior to those of existing methods. Additionally, the method was used to compare the baseline thiol profiles and oxidative stress responses of cell lines derived from different tissues. The results revealed a previously unreported response to oxidative stress in lens epithelial (B3) cells, which may be exploited as a new therapeutic target for oxidative-stress-related ocular diseases. Further application of this method may uncover new pathways involved in oxidative-stress-related diseases and endogenous defense mechanisms.

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Section: Resultssupporting

confidence: 91%

Section: Resultssupporting

confidence: 86%

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Extensive Thiol Profiling for Assessment of Intracellular Redox Status in Cultured Cells by HPLC-MS/MS

Chernatynskaya

Pfaff

et al. 2021

Antioxidants

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“…All thiol drugs scavenge reactive oxygen species (ROS) and inhibit ROS-mediated inflammation in redox reactions that occur independently of their abilities to cleave cystine. Their anti-inflammatory actions are related to ROS scavenging, but a subset of thiol drugs have additional anti-oxidant or anti-inflammatory effects related to their ability to replenish glutathione directly (NAC, as a precursor) or indirectly (cysteamine, bucillamine, tiopronin) or ability to inhibit pro-inflammatory mediators (49,(55)(56)(57)(58). For example, Mesna, tiopronin and D-penicillamine inhibit myeloperoxidase (16,17) and, as noted above, cysteamine inhibits TG2 and somatostatin.…”

Section: Discussionmentioning

confidence: 99%

Thiol drugs decrease SARS-CoV-2 lung injuryin vivoand disrupt SARS-CoV-2 spike complex binding to ACE2in vitro

Khanna

Raymond

Charbit

et al. 2020

Preprint

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Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the SARS-CoV-2 spike protein is an envelope glycoprotein that binds angiotensin converting enzyme 2 as an entry receptor. The capacity of enveloped viruses to infect host cells depends on a precise thiol/disulfide balance in their surface glycoprotein complexes. To determine if cystines in the SARS-CoV-2 spike protein maintain a native binding interface that can be disrupted by drugs that cleave cystines, we tested if thiol-based drugs have efficacy in receptor binding and cell infection assays. We found that thiol-based drugs, cysteamine and WR-1065 (the active metabolite of amifostine) in particular, decrease binding of SARS-CoV-2 spike protein to its receptor, decrease the entry efficiency of SARS-CoV-2 spike pseudotyped virus, and inhibit SARS-CoV-2 live virus infection. Our findings uncover a vulnerability of SARS-CoV-2 to thiol-based drugs and provide rationale to test thiol-based drugs, especially cysteamine and amifostine, as novel treatments for COVID-19.One Sentence SummaryThiol-based drugs decrease binding of SARS-CoV-2 spike protein to its receptor and inhibit SARS-CoV-2 cell entry.

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“…NO. 1953-02-2, and chemical name, N -(2-mercaptopropionyl) glycine, Figure ] is a pharmaceutically important compound with weak acidity. , Because tiopronin is an important antioxidant and the most abundant nonprotein thiol in the human body, the mechanism of its action in medical effect is the direct scavenging of free radicals and maintenance of healthy levels of glutathione. , It could be used to protect against ischemic/reperfusion-mediated injury and against radiation-induced damages, even at low doses. , In addition, tiopronin is also used in the treatment of cystinuria and rheumatoid arthritis since the 1980s in Western countries. , In China, it was used to protect against numerous liver diseases, including fatty liver disease, drug-induced liver injury, and viral hepatitis as well as an antidote to heavy metal poisoning. − …”

Section: Introductionmentioning

confidence: 99%

Solubility Measurement of Tiopronin in Four Mixed Solvents at 273.15–318.15 K and Correlation Using Thermodynamic Models

Xin

Gao

2021

J. Chem. Eng. Data

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The solubility data of tiopronin in four binary mixtures in the temperature range from 273.15 to 318.15 K were obtained using the isothermal saturation method under 101.3 kPa. In mixtures of 1-butanol + toluene and 1-butanol + acetonitrile, the mole solubility data increased monotonically with the increasing mass fraction of 1-butanol at a certain temperature. In addition, it increased to the maximum and then decreased with the increasing mass fraction of i-butanol in systems of i-butanol + toluene and i-butanol + acetonitrile. The maximum values in mixtures of 1-butanol + toluene and 1-butanol + acetonitrile were all obtained in pure 1-butanol (0.103 at 318.15 K), while these data in systems of i-butanol + toluene and i-butanol + acetonitrile were 4.644 × 10–2 and 5.243 × 10–2 at 318.15 K, respectively. The solubility data were correlated using the Jouyban–Acree model and CNIBS/R–K model. The maximum relative average deviation value was no more than 5%. In addition, the square of the linear correlation coefficient between experimental and calculated values is closer to 1. Therefore, the Jouyban–Acree model is suitable to correlate the solubility values of tiopronin in selected binary mixtures at studied temperatures. The solubility data and model parameters were important for the preparation and purification of tiopronin.

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Protective effects of tiopronin on oxidatively challenged human lung carcinoma cells (A549)

Cited by 10 publications

References 41 publications

Extensive Thiol Profiling for Assessment of Intracellular Redox Status in Cultured Cells by HPLC-MS/MS

Extensive Thiol Profiling for Assessment of Intracellular Redox Status in Cultured Cells by HPLC-MS/MS

Thiol drugs decrease SARS-CoV-2 lung injuryin vivoand disrupt SARS-CoV-2 spike complex binding to ACE2in vitro

Solubility Measurement of Tiopronin in Four Mixed Solvents at 273.15–318.15 K and Correlation Using Thermodynamic Models

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