scholarly journals Gliclazide Does Not Fully Prevent 2-Deoxy-D-Ribose-Induced Oxidative Damage Because It Does Not Restore Glutathione Content in a Pancreaticβ-Cell Line

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Gwanpyo Koh ◽  
Min-Kyoung Kim ◽  
Eun-Jin Yang ◽  
Dae-Ho Lee
Keyword(s):  
Flow Cytometry ◽  
Oxidative Damage ◽  
Cell Line ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Annexin V ◽  
Blue Staining ◽  
Similar Degree ◽  
Free System ◽  
Intracellular Glutathione

We compared the effects of gliclazide, an antidiabetic agent with antioxidant properties, andN-acetyl-L-cysteine (NAC), a glutathione precursor, in protecting against 2-deoxy-D-ribose- (dRib-) induced oxidative damage in HIT-T15 cells. Using trypan blue staining and flow cytometry with annexin V/PI staining, gliclazide treatment slightly reversed dRib-induced cell death and apoptosis, and NAC treatment markedly reduced both measures. Likewise, flow cytometry using DHR 123 staining showed that the levels of dRib-induced reactive oxygen species (ROS) were partially suppressed by gliclazide and completely inhibited by NAC. Using electron spin resonance spectrometry, gliclazide and NAC scavenged hydroxyl radicals generated by Fenton reaction to a similar degree in a cell-free system. NAC, but not gliclazide, completely restored the intracellular glutathione depleted by dRib using monochlorobimane fluorescence and glutathione assays. Thus, gliclazide treatment suppressed dRib-induced oxidative damage in HIT-T15 cells less than NAC did because gliclazide did not restore the intracellular glutathione content as effectively as NAC. In addition, the elevation of intracellular glutathione rather than free radical scavenging might be an important mechanism for protecting against dRib-induced oxidative damage in aβ-cell line.

scholarly journals Ethanol Extract of Maclura tricuspidata Fruit Protects SH-SY5Y Neuroblastoma Cells against H2O2-Induced Oxidative Damage via Inhibiting MAPK and NF-κB Signaling

2021 ◽  
Vol 22 (13) ◽  
pp. 6946
Author(s):  
Weishun Tian ◽  
Suyoung Heo ◽  
Dae-Woon Kim ◽  
In-Shik Kim ◽  
Dongchoon Ahn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Oxidative Damage ◽  
Cell Damage ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Biologically Active ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Neuroprotective Effects

Free radical generation and oxidative stress push forward an immense influence on the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Maclura tricuspidata fruit (MT) contains many biologically active substances, including compounds with antioxidant properties. The current study aimed to investigate the neuroprotective effects of MT fruit on hydrogen peroxide (H2O2)-induced neurotoxicity in SH-SY5Y cells. SH-SY5Y cells were pretreated with MT, and cell damage was induced by H2O2. First, the chemical composition and free radical scavenging properties of MT were analyzed. MT attenuated oxidative stress-induced damage in cells based on the assessment of cell viability. The H2O2-induced toxicity caused by ROS production and lactate dehydrogenase (LDH) release was ameliorated by MT pretreatment. MT also promoted an increase in the expression of genes encoding the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). MT pretreatment was associated with an increase in the expression of neuronal genes downregulated by H2O2. Mechanistically, MT dramatically suppressed H2O2-induced Bcl-2 downregulation, Bax upregulation, apoptotic factor caspase-3 activation, Mitogen-activated protein kinase (MAPK) (JNK, ERK, and p38), and Nuclear factor-κB (NF-κB) activation, thereby preventing H2O2-induced neurotoxicity. These results indicate that MT has protective effects against H2O2-induced oxidative damage in SH-SY5Y cells and can be used to prevent and protect against neurodegeneration.

scholarly journals Geigerin-induced cytotoxicity in a murine myoblast cell line (C2C12)

2017 ◽  
Vol 84 (1) ◽  
Author(s):  
Christo J. Botha ◽  
Sarah J. Clift ◽  
Gezina C.H. Ferreira ◽  
Mxolisi G. Masango
Keyword(s):  
Flow Cytometry ◽  
Cell Line ◽  
Ethical Issues ◽  
Sesquiterpene Lactones ◽  
Annexin V ◽  
Metabolic Activation ◽  
Suitable Model ◽  
Myoblast Cell Line ◽  
Myoblast Cell

Geigeria poisoning in sheep, locally known as ‘vermeersiekte’, is an economically important plant poisoning in southern Africa. The toxic principles contained by the toxic plants are believed to be several sesquiterpene lactones, such as geigerin, vermeeric acid and vermeerin, which cause striated muscle lesions in small stock. Because of ethical issues surrounding the use of live animals in toxicity studies, there is currently a dire need to establish an in vitro model that can be used to replace traditional animal experimentation. The objective of this study was to determine the cytotoxicity of geigerin in a murine myoblast cell line (C2C12) using methyl-thiazol-tetrazolium (MTT) and lactate dehydrogenase (LDH) assays, annexin V and propidium iodide (PI) flow cytometry and transmission electron microscopy (TEM). Mouse myoblasts were exposed to 2.0 mM, 2.5 mM and 5.0 mM geigerin for 24, 48 and 72 h. A concentration-dependent cytotoxic response was observed. Apoptosis was detected by means of annexin V flow cytometry during the first 24 h and apoptotic bodies were also visible on TEM. According to the LDH and PI flow cytometry results, myoblast cell membranes were not injured. We concluded that the murine myoblast cell line (C2C12) is a suitable model for future studies planned to evaluate the cytotoxicity of other and combinations of sesquiterpene lactones, with and without metabolic activation, implicated in ‘vermeersiekte’ and to elucidate the subcellular effects of these myotoxins on cultured myoblasts.

Radical-scavenging abilities and antioxidant properties of theaflavins and their gallate esters in H2O2-mediated oxidative damage system in the HPF-1 cells

2008 ◽  
Vol 22 (5) ◽  
pp. 1250-1256 ◽  
Author(s):  
Ziyin Yang ◽  
Guoliang Jie ◽  
Fang Dong ◽  
Yi Xu ◽  
Naoharu Watanabe ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Antioxidant Properties ◽  
Radical Scavenging

Comparison of the antioxidant properties of emu oil with other avian oils

2008 ◽  
Vol 48 (10) ◽  
pp. 1345 ◽  
Author(s):  
Darin C. Bennett ◽  
William E. Code ◽  
David V. Godin ◽  
Kimberly M. Cheng
Keyword(s):  
Oxidative Damage ◽  
Radical Scavenging Activity ◽  
Biological Membrane ◽  
Saturated Fatty Acids ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Thiobarbituric Acid Reactive Substance ◽  
Scavenging Activity ◽  
Triglyceride Fraction ◽  
Emu Oil

The antioxidant properties of emu oil were compared with oils derived from the fat of other avian species. We first examined their free radical scavenging activity against the 2,2-diphenyl-1-picryl hydracyl radical. The concentration of emu oil in the test solution that caused 50% neutralisation (IC50) was variable (24.5 ± 5.9 mg/mL, range 5.3–55.4 mg/mL), but similar to values obtained for other ratites (10.7 ± 5.9 mg/mL). In contrast, the IC50 values for duck and chicken oil were much higher (118.0 ± 8.1 mg/mL). The variability in the radical scavenging activity of emu oil preparations may reflect variations in the diets of the birds, the processing protocol and/or the storage age of the oil. We also evaluated some of the ratite oils for their inhibitory capacity on human erythrocyte membrane oxidation, by measuring the reduction of the thiobarbituric acid-reactive substance (TBAR) production. Emu oil had a greater effect in decreasing TBAR production than either the ostrich or rhea oil, suggesting that it offers more protection than the other ratite oils against oxidative damage. In conclusion, we demonstrated that emu oil has both antioxidant properties in vitro and a protective role against oxidative damage in a model biological membrane system. The antioxidant or radical scavenging properties of emu oil appear to be due to minor constituents in the non-triglyceride fraction of the oil, while its high ratio of unsaturated to saturated fatty acids (UFA : SFA) offers protection against oxidative damage.

Evaluation of thymoquinone (TQ) as an antiproliferative, proapoptotic, and immunomodulatory agent in a non-small cell lung cancer cell (NSCLC) line

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14644-e14644
Author(s):  
S. H. Jafri ◽  
J. Glass ◽  
R. Shi ◽  
H. Kleiner
Keyword(s):  
Flow Cytometry ◽  
Cell Growth ◽  
Cell Line ◽  
Mtt Assay ◽  
Statistical Significance ◽  
Control Cell ◽  
Annexin V ◽  
Nsclc Cell ◽  
Antibody Array ◽  
Nsclc Cell Line

e14644 Background: NSCLC is the most common cause of cancer death worldwide. We performed in vitro testing of Thymoquinone (TQ), a derivative of black caraway seed against NSCLC cell line NCI-H460 Methods: Cells were grown in RPMI and were plated at a density of 5,000 cells per well in a 96 well plate and cell growth determined in the presence of 80 and 100μM of TQ dissolved in DMSO with appropriate solvent only as control. Cell proliferation was determined at 24, 48 and 72 hrs intervals using 3-(4,5-dimethyltiazol 2-yl)-2,5-diphenyltetraolium bromide (MTT) assay. Factorial analyses of variance (ANOVA) were used to determine the effect of TQ and control with the time. Student-Newman-Keuls test was used to determine statistical significance with P value <0.05 considered significant. Apoptosis was detected using Annexin V-FITC Aptosis Detection Kit analyzing the effects of TQ at 24 hrs after treatment by flow cytometry. The immunomodulatory effects of TQ were tested using RayBio Human Cytokine Antibody Array C series 200. NCI-H460 cells (50,000 cells per well in duplicate 6 well plates) were grown in serum free RPMI media. 24 hrs after treatment with TQ or DMSO media was collected and analyzed for expression of various cytokines. Results: The MTT assay showed that TQ at 80 and 100 μM significantly inhibited cell growth as compared to control and at 24 hrs for example, 100 μM TQ inhibited cell growth by 78%. Apoptosis occurred rapidly after treatment with TQ with 73.5% of cells being positive for expression of Annexin-V as detected by flow cytometry after 24 hrs of exposure to TQ as compared to 2.6% of controls. The cytokine array revealed that TQ significantly decreased expression of ENA-78(Epithelial neutrophil activating peptide), and GRO (Growth related oncogene).ENA-78 is correlated with vascularity and tumor growth in NSCLC tumor, whereas GRO is associated with neoangiogenesis. Conclusions: TQ is shown to be a powerful anti-proliferative, pro-apoptotic and anti- angiogenic agent in a NSCLC cell line. No significant financial relationships to disclose.

MNPs-Fe3o4 Induce Leukemia Cell Apoptosis by Oxidative Stress

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4304-4304
Author(s):  
Ying Wang ◽  
Bao-An Chen ◽  
Guo-hua Xia ◽  
Ziying Jian ◽  
Zhi Li ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Leukemia Cell ◽  
Annexin V ◽  
Giemsa Staining ◽  
Blue Staining ◽  
Control Group ◽  
G1 Arrest ◽  
U937 Cells ◽  
Normal Monocyte ◽  
Safe Concentration

Abstract Abstract 4304 The present study evaluated on the safe concentration for normal monocyte cells whether the magnetic nanoparticles of Fe3O4 (MNPs-Fe3O4) could induce caspase3-dependent apoptosis in SKM1 cells and U937 cells by oxidative damage. The average sizes of the particles were carefully determined by transmission electron microscopy. The viability of the cells after exposed to different concentration MNPs-Fe3O4 for 12h, 24h, 48h and 72h were detected by trypan blue staining. Cell cycle after exposure for 72h was analysed by propidium iodide (PI) staining. Apoptosis of MNPs-Fe3O4 group were detected and determined by Annexin V-FITC/PI double staining, 5,5’,6,6’-tetrachloro-1, 1’,3,3’-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) probe and Wright - Giemsa staining. ROS in SKM1 cells and U937 cells after exposure were determined by flow cytometry after dichlorofluoroescein diacetate (DCFH-DA) staining. The changes of caspase3, survivin and bcl-rambo in the cells treatment with MNPs-Fe3O4 with or wtihout trolox for 48 hours were detected by western blot analysis. The significant decreased of cell viability caused by 100 μ M MNPS-Fe3O4 exposure were observed in SKM1 cells and u937 cells, not in normal monocytes cells (p < 0.05), the exposure also induced the SKM1 cells and u937 cells G0/G1 arrest (p < 0.05). Annexin V / PI staining assay show that 100 μ M MNPs-Fe3O4 group appeared more apoptosic rate in the U937 and SKM1 cells than the control group (p < 0.05), and on the same exposed concentration the apoptotic bodies could be frequently found in the U937 and SKM1 cells, while not in normal monocyte cells by Wright - Giemsa staining. The mitochondrial membrane potential in the two kinds of cells significantly decreased after exposed 100 μ M MNPs-Fe3O4 for 24h (p < 0.05), while pretreated with antioxidants trolox, the change was allevated (p < 0.05). DCFH-DA assay show that reactive oxygen species (ROS) generation increased in 6h of exposure in SKM1 cells and U937 cells (p < 0.05). Our results also showed the particle induced caspase3-dependent apoptosis in the SKM1 cells and U937 cells, while did not in normal monocyte cells, and increasing expression of bcl-rambo and decreasing expression of survivin involve in the process. These results suggest that on the safe concentration for normal monocyte cells MNPs-Fe3O4 could induce caspase3-dependent apoptosis in SKM1 cells and U937 cells by oxidative damage, moreover, increasing expression of bcl-rambo and decreasing expression of survivin involve in the process. Disclosures: No relevant conflicts of interest to declare.

Modulatory effects of Moringa oleifera extracts against hydrogen peroxide-induced cytotoxicity and oxidative damage

2010 ◽  
Vol 30 (9) ◽  
pp. 1359-1368 ◽  
Author(s):  
S Sreelatha ◽  
PR Padma
Keyword(s):  
Hydrogen Peroxide ◽  
Dna Damage ◽  
Antioxidant Activity ◽  
Oxidative Damage ◽  
Moringa Oleifera ◽  
Oxidative Dna Damage ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Kb Cells ◽  
Leaf Extracts

Studies have demonstrated that the induction of oxidative stress may be involved in oxidative DNA damage. The present study examined and assessed the hydrogen peroxide (H2O2)-mediated DNA damage in human tumor KB cells and also assessed the ability of Moringa oleifera leaf extracts to inhibit the oxidative damage. H2O2 imposed a stress on the membrane lipids which was quantified by the extent of thiobarbituric acid reactive substances (TBARS) formed. The leaf extracts caused a very significant inhibition of the extent of LPO formation and enhanced the activity of antioxidative enzymes such as superoxide dismutase (SOD) and catalase (CAT) in KB cells. The comet assay was employed to study the DNA damage and its inhibition by the leaf extracts. H2O2 caused a significant increase in the number of cells bearing comets, resulting in significant DNA damage. The leaf extracts significantly reduced the incidence of comets in the oxidant stressed cells. The extent of cytotoxicity of H2O2 in the presence and the absence of leaf extracts studied in KB tumor cells by the MTT assay showed that H2O2 caused a marked decrease in the viability of KB cells where as the leaf extracts effectively increased the viability of assaulted KB cells. The observed cytoprotective activity is probably due to the antioxidant properties of its constituents, mainly phenolics. Total phenolics showed higher correlation with antioxidant activity. The leaf extracts showed higher antioxidant activity than the reference compound. These results suggest that the inhibition by the leaf extracts on oxidative DNA damage could be attributed to their free radical scavenging activities and the effect evidenced in KB cells can be in part correlated to a modulation of redox-sensitive mechanisms.

scholarly journals In-vitro, in-vivo, and in-silico assessment of radical scavenging and cytotoxic activities of Oliveria decumbens essential oil and its main components

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tahereh Jamali ◽  
Gholamreza Kavoosi ◽  
Yousef Jamali ◽  
Saeed Mortezazadeh ◽  
Susan K. Ardestani
Keyword(s):  
Nitric Oxide ◽  
Flow Cytometry ◽  
Essential Oil ◽  
Cancer Cells ◽  
In Silico ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Main Components

AbstractWe aimed to explore and compare new insights on the pharmacological potential of Oliveria decumbence essential oil (OEO) and its main components highlighting their antioxidant activity in-vitro, in-vivo, and in-silico and also cytotoxic effects of OEO against A549 lung cancer cells. At first, based on GC–MS analysis, thymol, carvacrol, p-cymene, and γ-terpinene were introduced as basic ingredients of OEO and their in-vitro antioxidant capacity was considered by standard methods. Collectively, OEO exhibited strong antioxidant properties even more than its components. In LPS-stimulated macrophages treated with OEO, the reduction of ROS (Reactive-oxygen-species) and NO (nitric-oxide) and down-regulation of iNOS (inducible nitric-oxide-synthase) and NOX (NADPH-oxidase) mRNA expression was observed and compared with that of OEO components. According to the results, OEO, thymol, and carvacrol exhibited the highest radical scavenging potency compared to p-cymene, and γ-terpinene. In-silico Molecular-Docking and Molecular-Dynamics simulation indicated that thymol and carvacrol but no p-cymene and γ-terpinene may establish coordinative bonds in iNOS active site and thereby inhibit iNOS. However, they did not show any evidence for NOX inhibition. In the following, MTT assay showed that OEO induces cytotoxicity in A549 cancer cells despite having a limited effect on L929 normal cells. Apoptotic death and its dependence on caspase-3 activity and Bax/Bcl2 ratio in OEO-treated cells were established by fluorescence microscopy, flow cytometry, colorimetric assay, and western blot analysis. Additionally, flow cytometry studies demonstrated increased levels of ROS in OEO-treated cells. Therefore, OEO, despite showing antioxidant properties, induces apoptosis in cancer cells by increasing ROS levels. Collectively, our results provided new insight into the usage of OEO and main components, thymol, and carvacrol, into the development of novel antioxidant and anti-cancer agents.

scholarly journals Effects of Apigenin and Apigenin- Loaded Nanogel on Induction of Apoptosis in Human Chronic Myeloid Leukemia Cells

2018 ◽  
Vol 7 ◽  
pp. e1008
Author(s):  
Mehrdad Hashemi ◽  
Nooshin Samadian
Keyword(s):  
Drug Delivery ◽  
Flow Cytometry ◽  
Chronic Myeloid Leukemia ◽  
Cell Line ◽  
K562 Cell ◽  
Myeloid Leukemia ◽  
Toxic Effects ◽  
Blue Staining ◽  
K562 Cell Line ◽  
Laboratory Conditions

Background: Diet plays an important role in cancer prevention. Apigenin, a flavonoid with thechemical formula C15H10O5, is abundantly present in vegetables. Vegetarian foods containing flavonoids are rich sources of bioactive compounds. Flavonoids have been utilized in herbal treatment. Nanogels are drug delivery systems based on polymers and are used in tissue engineering and for drug delivery. This study was conducted to compare the effects of apigenin and a nanodrug on the viability of the K562 cell line of chronic myeloid leukemia at different durations under laboratory conditions. Materials and Methods: Chitosan was first dissolved in 1% acetic acid, and  ethylene dichloride EDC and NHS were added to the solution. Then, the nanodrug was prepared by loading apigenin into stearate–chitosan nanogel (scs nanogel), and its physical and morphological characteristics were evaluated by TEM, DLS, and FTIR. Trypan blue staining, MTT assay, and flow cytometry were used to analyze the effects of various concentrations of apigenin and apigenin-loaded chitosan–stearate nanogel (APG–SCS) at 24, 48, and 72 h after they were applied to the K562 cell line. Results: The diameter of the nanodrug particles was measured using DLS and confirmed by TEM. The K562 cells treated with APG–SCS and with apigenin exhibited significant differences compared with the control (P < 0.05). Apoptosis was detected by flow cytometry. Conclusion: This study showed that the toxic effects of apigenin and the nanodrug improved with increasing concentrations and exposure durations compared to those in the control.The toxic effect of apigenin loaded into the stearate-chitosan nanogel was greater than apigenin, and the toxic effects of both materials were greater compared to the control under laboratory conditions.[GMJ.2018;7:e1008]

Hepatotoxicity During Eltrombopag Administration Might Be Due to Necrosis of Hepatocytes

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2228-2228
Author(s):  
Kazunori Murai ◽  
Shugo Kowata ◽  
Akiko Abo ◽  
Tatsuo Oyake ◽  
Shigeki Ito ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Flow Cytometry ◽  
Growth Inhibition ◽  
Cell Line ◽  
Mtt Assay ◽  
Annexin V ◽  
Similar Data ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Annexin V Assay

Abstract Abstract 2228 Background: Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of immune thrombocytopenic patients who are refractory to the medications including corticosteroid. In RAISE study (The Lancet 2011: 377; 393–402), 79% patients in the eltrombopag group responded to treatment at least once during the study. However, 7% of eltrombopag-treated patients had increase of alanine aminotransferase (ALT) concentration and 4% of total bilirubin. The mechanism of eltrombopag-induced hepatobiliary toxicity remains unknown. In this study, we evaluated the effects of eltrombopag on hepatocytes using HepG2, human hepatocellular carcinoma cell line. Method: Cell proliferation was analyzed by MTT assay. Analysis of apoptosis/necrosis was analyzed by flow cytometry assay using Annexin V and propium iodide (PI) (Annexin-/PI-, viable cells; Annexin+/PI-, early apoptosis cells; Annexin+/PI+, late apoptosis and necrosis cells; Annexin-/PI+, late necrosis cells). Reduced glutathione was measured by DTNB colorimetric method. Murine hepatoma cell line Hepa 1–6 and murine normal liver derived cell line NCTC clone 1469 were also used in this study. Results: HepG2 was incubated with eltrombopag for 72 hrs and then MTT assay was performed. Figure 1a showed the growth inhibition curve of HepG2. HepG2 growth was suppressed by eltrombopag in a dose dependent manner (Figure 1a: without NAC, 12.5 μM 44.3 ± 8.7 %). In the addition of N-acetylcysteine (NAC) canceled the inhibitory effect (Figure 1a: with NAC 10mM: 60.4 ± 22.3 % at 12.5μM eltrombopag, p<0.05). To investigate whether this suppression was due to apoptosis or necrosis, we used PI/ Annexin V assay using flow cytometry. Figure 1b showed that each cell fraction after 72 hrs incubation with eltrombopag. PI positive and PI negative fraction was markedly increased (0μM: 0.7 ± 0.4%, 12.5 μM: 8.0 ± 6.0% p<0.01, 25μM: 39.6 ± 12.2% p<0.001). To confirm that the inhibitory effects of eltrombopag might be due to necrosis, we used IM-54, which is inhibitory molecule against oxidative stress induced necrosis, in MTT assay and PI/ Annexin V assay. As shown in Figure 2 a and 2 b, IM-54 canceled the inhibitory effects of eltrombopag in MTT assay (IM-54 0μM: 18.3 ± 7.5 %, IM-54 10 μM: 33.9 ± 10.6 % at eltrombopag 25μM, p<0.01) and PI/Annexin V assay (IM-54 0μM: 48.3 ± 12.4 %, IM-54: 10 μM 74.2 ± 8.3 % in PI/Annexin V double negative fraction at eltrombopag 25μM, p<0.01). The addition of Caspase-Inhibitor III (Boc-D-FMK) did not cancel the growth inhibition by eltrombopag in MTT assey. We measured GSH concentration of HepG2 cells. After the treatment of eltrombopag for 72 hrs, GSH decreased at 12.5μM of eltrpmbopag, however IM-54 restored the GSH concentration (83 mM at IM-54 0μM and eltrombopag 0 μM, IM-54 0 μM: 42.0 mM and IM-54 10μM: 83.3 mM at eltrombopag 12.5μM). Similar data were obtained in the study using Hepa 1–6 and NCTC clone 1469. Conclusion: Basic structure of eltrombopag is similar to that of 3-bipheyl-carboxylic acid, which is a strong oxidizing agent. Taken together, eltrombopag have an oxidative stress on hepatocytes to result in hepatotoxicity. Disclosures: No relevant conflicts of interest to declare.

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