Acrylamide Induced Oxidative Cellular Senescence in Embryonic Fibroblast Cell Line (NIH 3T3): A Protection by Carvacrol

Background: Stress-induced cellular senescence is a perpetual state of cell cycle arrest occurring in proliferating cells in response to stressful conditions. It is believed that oxidative stress plays a unique role in this process. As a reactive chemical compound that can induce oxidative stress, acrylamide is widely applied in several fields. Carvacrol is a liquid phenolic monoterpenoid found in essential oils of some plants and is known for its antioxidant and anticarcinogenic properties. Objectives: The current study aimed to evaluate the effects of carvacrol on oxidative stress and cellular senescence induced by acrylamide in the NIH 3T3 cell line. Methods: NIH 3T3 embryonic fibroblast cells were exposed to different concentrations of acrylamide, carvacrol, and H2O2 in a cell culture medium. The level of β-galactosidase (SA-β-gal) activity, as a marker of cellular senescence, was measured using staining and quantitative assays. Furthermore, to measure oxidative stress parameters, the content of glutathione and lipid peroxidation were determined. Results: Acrylamide could induce premature senescence evident by the elevated lipid peroxidation and SA-β-gal activity and declined cell viability and glutathione. Moreover, carvacrol showed beneficial effects on both acrylamide- and H2O2-induced cellular senescence by significantly reversing or subsiding the effect of oxidative stress and mediating its consequences. Conclusions: It can be concluded that carvacrol has protective effects against oxidative cellular senescence induced by acrylamide in the NIH 3T3 cell line.

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Design, Synthesis, In vitro and In silico Evaluation of New Hydrazonebased Antitumor Agents as Potent Akt Inhibitors

Letters in Drug Design & Discovery ◽

10.2174/1570180817999200618163507 ◽

2020 ◽

Vol 17 (11) ◽

pp. 1380-1392

Author(s):

Emine Merve Güngör ◽

Mehlika Dilek Altıntop ◽

Belgin Sever ◽

Gülşen Akalın Çiftçi

Keyword(s):

Cell Line ◽

Anticancer Agents ◽

In Silico ◽

Antitumor Agents ◽

Colorimetric Assay ◽

Fibroblast Cell ◽

Lipinski’S Rule ◽

In Silico Docking ◽

Embryonic Fibroblast

Background: Akt is overexpressed or activated in a variety of human cancers, including gliomas, lung, breast, ovarian, gastric and pancreatic carcinomas. Akt inhibition leads to the induction of apoptosis and inhibition of tumor growth and therefore extensive efforts have been devoted to the discovery of potent antitumor drugs targeting Akt. Objectives: The objective of this work was to identify potent anticancer agents targeting Akt. Methods: New hydrazone derivatives were synthesized and investigated for their cytotoxic effects on 5RP7 H-ras oncogene transformed rat embryonic fibroblast and L929 mouse embryonic fibroblast cell lines. Besides, the apoptotic effects of the most active compounds on 5RP7 cell line were evaluated using flow cytometry. Their Akt inhibitory effects were also investigated using a colorimetric assay. In silico docking and Absorption, Distribution, Metabolism and Excretion (ADME) studies were also performed using Schrödinger’s Maestro molecular modeling package. Results and Discussion: Compounds 3a, 3d, 3g and 3j were found to be effective on 5RP7 cells (with IC50 values of <0.97, <0.97, 1.13±0.06 and <0.97 μg/mL, respectively) when compared with cisplatin (IC50= 1.87±0.15 μg/mL). It was determined that these four compounds significantly induced apoptosis in 5RP7 cell line. Among them, N'-benzylidene-2-[(4-(4-methoxyphenyl)pyrimidin- 2-yl)thio]acetohydrazide (3g) significantly inhibited Akt (IC50= 0.5±0.08 μg/mL) when compared with GSK690693 (IC50= 0.6±0.05 μg/mL). Docking studies suggested that compound 3g showed good affinity to the active site of Akt (PDB code: 2JDO). According to in silico ADME studies, the compound also complies with Lipinski's rule of five and Jorgensen's rule of three. Conclusion: Compound 3g stands out as a potential orally bioavailable cytotoxic agent and apoptosis inducer targeting Akt.

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Comparative study of a new composite biomaterial fluor-hydroxyapatite on fibroblast cell line NIH-3T3 by direct test

Biologia ◽

10.2478/s11756-008-0043-x ◽

2008 ◽

Vol 63 (2) ◽

Cited By ~ 6

Author(s):

Marica Theiszová ◽

Soňa Jantová ◽

Silvia Letašiová ◽

Ľuboš Valík ◽

Martin Palou

Keyword(s):

Comparative Study ◽

Cell Line ◽

Dna Content ◽

Fibroblast Cell ◽

Cell Number ◽

Fibroblast Cell Line ◽

3T3 Cells ◽

End Points ◽

Basal Cytotoxicity ◽

Nih 3T3

AbstractThe number of biomaterials used in biomedical applications has rapidly increased in the past two decades. Fluorapatite (FA) is one of the inorganic constituents of bone or teeth used for hard tissue repairs and replacements. Fluor-hydroxyapatite (FHA) is a new synthetically prepared composite that in its structure contains the same molecular concentration of OH− groups and F− ions. The aim of this experimental investigation was to use the embryonal mouse fibroblast cell line NIH-3T3 for comparative study of basal cytotoxicity of fluoridated biomaterials FHA and FA discs. Hydroxyapatite (HA) disc, high-density polyethylene as negative control and polyvinyl chloride (PVC) containing organotin stabilizer as positive control were used as standard biomaterials. The appropriateness of the use of NIH-3T3 cells and their sensitivity for tested biomaterials were evaluated on the basis of five cytotoxic end points: cell proliferation, cell morphology, lactate dehydrogenase (LDH) released, protein and DNA cell content. The basal cytotoxicity of FHA, FA and HA discs was measured by direct contact method. FHA composite, FA and HA demonstrated in cell line NIH-3T3 nearly similar basal cytotoxicity increasing with the time of treatment. After 72 h of biomaterials treatment, about 25% inhibition of cell number, unchanged morphology of dividing cells, 6.31–0.16% increase of released LDH, about 10% inhibition of cell protein content and about 20% inhibition of DNA content was found. On the other hand, from the growth rates it resulted that NIH-3T3 cells, affected by tested biomaterials, divided about 20% slowlier than the control (untreated cells). Using the linear regression analysis we found out that deviations in measurements of cytotoxicity by four methods were as follows: less than 10% for cell number, protein and DNA content methods and 12.4% for released LDH method. Based on a good correlation of the cytotoxicity of biomaterials obtained from all end points we could conclude that fibroblast NIH-3T3 cell line was appropriate for measuring the basal cytoxicity of tested biomaterials.

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Attenuation of erythrocyte membrane oxidative stress bySesbania grandiflorain streptozotocin-induced diabetic rats

Biochemistry and Cell Biology ◽

10.1139/bcb-2015-0039 ◽

2015 ◽

Vol 93 (4) ◽

pp. 385-395 ◽

Cited By ~ 7

Author(s):

Chandrabose Sureka ◽

Thiyagarajan Ramesh ◽

Vavamohaideen Hazeena Begum

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Blood Glucose ◽

Erythrocyte Membrane ◽

Osmotic Fragility ◽

Diabetic Rats ◽

Glycosylated Haemoglobin ◽

Albino Rats ◽

Enzymatic Antioxidants ◽

Protective Effects

The aim of the present study was to investigate the protective effects of Sesbania grandiflora flower (SGF) extract on erythrocyte membrane in Streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 190–220 g, were made diabetic by an intraperitonial administration of STZ (45 mg/kg). Normal and diabetic rats were treated with SGF, and diabetic rats were also treated with glibenclamide as drug control, for 45 days. In this study plasma insulin and haemoglobin levels were decreased and blood glucose, glycosylated haemoglobin, protein oxidation, lipid peroxidation markers, and osmotic fragility levels were increased in diabetic rats. Moreover, erythrocytes antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxide, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase activities and non-enzymatic antioxidants such as vitamin C, vitamin E, reduced glutathione (GSH), and oxidized glutathione (GSSG) levels were altered. Similarly, the activities of total ATPases, Na+/K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase were also decreased in the erythrocytes of diabetic rats. Administration of SGF to STZ-induced diabetic rats reduced blood glucose and glycosylated haemoglobin levels with increased levels of insulin and haemoglobin. Moreover, SGF reversed the protein and lipid peroxidation markers, osmotic fragility, membrane-bound ATPases activities, and antioxidant status in STZ-induced diabetic rats. These results suggest that SGF could provide a protective effect on diabetes by decreasing oxidative stress-associated diabetic complications.

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Notoginsenoside R1 Ameliorates Diabetic Retinopathy through PINK1-Dependent Activation of Mitophagy

Cells ◽

10.3390/cells8030213 ◽

2019 ◽

Vol 8 (3) ◽

pp. 213 ◽

Cited By ~ 15

Author(s):

Ping Zhou ◽

Weijie Xie ◽

Xiangbao Meng ◽

Yadong Zhai ◽

Xi Dong ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Retinopathy ◽

Oral Treatment ◽

Müller Cells ◽

Panax Notoginseng ◽

Protective Effects ◽

Muller Cells ◽

Beneficial Effects ◽

Pre Treatment ◽

Lc3 Puncta

: Accumulating evidence has indicated that inflammation, oxidative stress, apoptosis, and autophagy in retinal Müller cells are involved in diabetic retinopathy (DR). Notoginsenoside R1 (NGR1), a novel saponin extracted from Panax notoginseng, posesses pharmacological properties, including treating diabetic encephalopathy and improving microcirculatory disorders. Nevertheless, its beneficial effects on DR and the potential mechanism remain to be elucidated. In this study, we found retinal vascular degeneration, reduced retinal thickness, and impaired retinal function in db/db mice were all dramatically attenuated by oral treatment with NGR1 (30 mg/kg) for 12 weeks. NGR1 pretreatment also significantly inhibited apoptosis, markedly suppressed the VEGF expression, markedly increased PEDF expression and markedly inhibited oxidative stress and inflammation in rat retinal Müller cells (rMC-1) subjected to high glucose (HG) and in the retinas of db/db mice. Furthermore, NGR1 pre-treatment upregulated the level of PINK1 and Parkin, increased the LC3-II/LC3-I ratio, and downregulated the level of p62/SQSTM1 in rMC-1 cells induced by HG and in the retinas of db/db mice. Moreover, NGR1 administration enhanced the co-localization of GFP-LC3 puncta and MitoTracker in rMC-1 cells. Importantly, knockdown of PINK1 abolished the protective effects of NGR1. In conclusion, these phenomena suggested that NGR1 prevented DR via PINK1-dependent enhancement of mitophagy.

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Effect of lead on proliferation, oxidative stress and genotoxic damage of 3T3-L1 fibroblasts

Toxicology Research ◽

10.1093/toxres/tfaa018 ◽

2020 ◽

Vol 9 (3) ◽

pp. 158-163

Author(s):

Claudia Noemi Martini ◽

Fernando Nicolás Sosa ◽

Julio Fuchs ◽

María del Carmen Vila

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Cell Line ◽

Public Health Problem ◽

Cell Counting ◽

Trypan Blue Exclusion ◽

Genotoxic Damage ◽

Trypan Blue Exclusion Assay ◽

A Cell ◽

Increase Lipid Peroxidation

Abstract Lead (Pb) is an environmental and industrial contaminant that still represents a public health problem. In this paper, we investigated the effect of Pb on proliferation, lipid peroxidation and the number of micronucleated cells in exponentially growing 3T3-L1 fibroblasts, a cell line previously used to evaluate different environmental contaminants. We found that Pb (10 μM or higher) was able to inhibit proliferation of exponentially growing cells after 24-h treatment, which was evaluated by the MTT assay and cell counting in Neubauer chamber, but cell survival was not affected according to the trypan blue exclusion assay. On the other hand, Pb was able to increase lipid peroxidation and the number of micronucleated cells, which are indicative of oxidative stress and genotoxic damage respectively. We also found that removal of Pb after 24-h treatment allowed cells to recover proliferation. Our results indicate that Pb was able to induce oxidative stress and genotoxicity in this cell line under standardized conditions, which supports the involvement of Pb in similar effects observed in human exposed to this heavy metal. In addition, Pb inhibits proliferation of exponentially growing fibroblasts but cells resume proliferation after removal of this metal, which suggests that it is important to move away Pb-exposed individuals from the source of contamination.

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Antioxidant Activity of Flavones from Scutellaria baicalensis in Lecithin Liposomes

Zeitschrift für Naturforschung C ◽

10.1515/znc-1997-11-1215 ◽

1997 ◽

Vol 52 (11-12) ◽

pp. 817-823 ◽

Cited By ~ 38

Author(s):

Janina Gabrielska ◽

Jan Oszmiańsk ◽

Romuald Żyłka ◽

Małgorzata Komorowska

Keyword(s):

Lipid Peroxidation ◽

Antioxidant Activity ◽

Skin Diseases ◽

Inhibitory Effect ◽

Scutellaria Baicalensis ◽

Butylated Hydroxytoluene ◽

Protective Effects ◽

Liposome Membrane ◽

Beneficial Effects ◽

Phosphatidylcholine Liposome

Abstract Trihydroxyflavones of Scutellaria baicalensis, Antioxidant Activity, Liposome, Peroxidation, MDA The antioxidant effect of a trihydroxyflavone extract from Scutellaria baicalensis on oxida tion induced by ultraviolet light, was studied with phosphatidylcholine liposome membrane. Also, as standards, the antioxidative activity of baicalin, wogonin, baicalein and butylated hydroxytoluene (BHT) was investigated. Comparison of the protective effects of thecompounds studied against photoinduced lipid peroxidation in lecithin liposome membranes showed that: (1) the inhibitory effect of those compounds (at 1.2 mol% antioxidant content in liposomes) on TBA reactive materials from lipid peroxidation decreased in the order of baicalin > BHT ≅ Scutellaria baicalensis. These were found much greater than wogonin and baicalein; (2) the depressed effect of those compounds (at 1.1 mol% compounds content in liposomes) on the production of conjugated dienes (proportional to oxidation index) could be classified as follows: Scutellaria baicalensis ≅ baicalin > BHT, these three were found more active much greather than baicalein and wogonin. Results obtained by ESR measurement confirm that Scutellaria baicalensis extract and the BHT compound significantly de pressed the effect of liposome oxidation. It was found that the new trihydroxyflavones of Scutellaria baicalensis, ensured a very satisfactory concentration-dependent protection of the liposome membrane against UV-induced oxidation. These findings suggest that some of the beneficial effects of the extract of the Scutellaria baicalensis can be mediated in certain diseases (for example in skin diseases) by their ability to scavenge free radicals and by their protective effect on lipid peroxidation caused by sunlight irradiation.

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Dehydroepiandrosterone Prevents H2O2-Induced BRL-3A Cell Oxidative Damage through Activation of PI3K/Akt Pathways rather than MAPK Pathways

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/2985956 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14

Author(s):

Longlong Li ◽

Yao Yao ◽

Zhihao Jiang ◽

Jinlong Zhao ◽

Ji Cao ◽

...

Keyword(s):

Oxidative Stress ◽

Protein Expression ◽

Signaling Pathways ◽

Hormone Receptors ◽

Mapk Signaling ◽

Ros Generation ◽

Protective Effects ◽

Pi3k Inhibitor Ly294002 ◽

Beneficial Effects

Dehydroepiandrosterone (DHEA) is a popular dietary supplement that has well-known benefits in animals and humans, but there is not enough information about the mechanisms underlying its effects. The present study aimed at investigating these mechanisms through in vitro experiments on the effects of DHEA on rat liver BRL-3A cells exposed to oxidative stress through H2O2. The findings showed that DHEA increased the antioxidant enzyme activity, decreased ROS generation, and inhibited apoptosis in H2O2-treated cells. These effects of DHEA were not observed when the cells were pretreated with known antagonists of sex hormones (Trilostane, Flutamide, or Fulvestrant). Furthermore, treatment with estradiol and testosterone did not have the same protective effects as DHEA. Thus, the beneficial effects of DHEA were associated with mechanisms that were independent of steroid hormone pathways. With regard to the mechanism underlying the antiapoptotic effect of DHEA, pretreatment with DHEA was found to induce a significant decrease in the protein expression of Bax and caspase-3 and a significant increase in the protein expression of PI3K and p-Akt in H2O2-treated BRL-3A cells. These effects of DHEA were abolished when the cells were pretreated with the PI3K inhibitor LY294002. No changes were observed on the p-ERK1/2, p-p38, and p-JNK protein levels in H2O2-induced BRL-3A cells pretreated with DHEA. In conclusion, our data demonstrate that DHEA protects BRL-3A cells against H2O2-induced oxidative stress and apoptosis through mechanisms that do not involve its biotransformation into steroid hormones or the activation of sex hormone receptors. Importantly, the protective effect of DHEA on BRL-3A cells was mainly associated with PI3K/Akt signaling pathways, rather than MAPK signaling pathways.

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Punicalagin Prevents Hypoxic Pulmonary Hypertension via Anti-Oxidant Effects in Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x16500439 ◽

2016 ◽

Vol 44 (04) ◽

pp. 785-801 ◽

Cited By ~ 13

Author(s):

Jingyun Shao ◽

Peng Wang ◽

An Liu ◽

Xusheng Du ◽

Jie Bai ◽

...

Keyword(s):

Oxidative Stress ◽

Pulmonary Hypertension ◽

Endothelial Dysfunction ◽

Pulmonary Arteries ◽

Pomegranate Juice ◽

No Production ◽

Protective Effects ◽

Hypoxic Pulmonary Hypertension ◽

Beneficial Effects ◽

Anti Oxidant

Punicalagin (PG), a major bioactive ingredient in pomegranate juice, has been proven to have anti-oxidative stress properties and to exert protective effects on acute lung injuries induced by lipopolysaccharides. This study aimed to investigate the effects of PG treatment on hypoxic pulmonary hypertension (HPH) and the underlying mechanisms responsible for the effects. Rats were exposed to 10% oxygen for 2 wk (8 h/day) to induce the HPH model. PG (5, 15, 45[Formula: see text]mg/kg) was orally administered 10[Formula: see text]min before hypoxia each day. PG treatments at the doses of 15 and 45[Formula: see text]mg/kg/d decreased the mean pulmonary arterial pressure (mPAP) and alleviated right ventricular hypertrophy and vascular remodeling in HPH rats. Meanwhile, PG treatment attenuated the hypoxia-induced endothelial dysfunction of pulmonary artery rings. The beneficial effects of PG treatment were associated with improved nitric oxide (NO)-cGMP signaling and reduced oxidative stress, as evidenced by decreased superoxide generation, gp91[Formula: see text] expression and nitrotyrosine content in the pulmonary arteries. Furthermore, tempol’s scavenging of oxidative stress also increased NO production and attenuated endothelial dysfunction and pulmonary hypertension in HPH rats. Combining tempol and PG did not exert additional beneficial effects compared to tempol alone. Our study indicated for the first time that PG treatment can protect against hypoxia-induced endothelial dysfunction and pulmonary hypertension in rats, which may be induced via its anti-oxidant actions.

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Protective effects of polysaccharide from Euphorbia kansui (Euphorbiaceae) on the swimming exercise-induced oxidative stress in mice

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y06-052 ◽

2006 ◽

Vol 84 (10) ◽

pp. 1071-1079 ◽

Cited By ~ 26

Author(s):

Farong Yu ◽

Shunqing Lu ◽

Fahong Yu ◽

Shutao Feng ◽

Peter M. McGuire ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Antioxidant Activities ◽

Oral Treatment ◽

Swimming Exercise ◽

Strenuous Exercise ◽

Antioxidant Enzyme Activities ◽

Protective Effects ◽

Euphorbia Kansui ◽

Exercise Induced

The present study examined the effects of derivatives of galactosides and glucosides in a polysaccharide extract from Euphorbia kansui (Euphorbiaceae) on exercise-induced oxidative stress in mice. Exhaustive swimming exercise significantly increases the degree of lipid peroxidation in terms of malondialdehyde content and reduces the antioxidant activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Our findings revealed that chronic oral treatment with the extract elevates enzymatic activities of SOD and GPx accompanied by a corresponding decrease in malondialdehyde. The antioxidative activities of these compounds against exercise-induced oxidative stress are correlated with various activities such as reducing the production of superoxide and hydroxyl radicals, inhibiting lipid peroxidation, enhancing antioxidative defenses, and increasing the production of SOD and GPx activity and expression in different tissues. These compounds may be involved in glycogen metabolism to meet the requirement of working skeletal muscles and act as antioxidants by terminating the chain reaction of lipid peroxidation to maintain the morphological stability of mitochondria in spinal motor neurons. These observations suggest that E. kansui has antioxidative and antifatigue properties and can be given as prophylactic and (or) therapeutic supplements for increasing antioxidant enzyme activities and preventing lipid peroxidation during strenuous exercise.

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L-Carnosine Stimulation of Coenzyme Q10 Biosynthesis Promotes Improved Mitochondrial Function and Decreases Hepatic Steatosis in Diabetic Conditions

Antioxidants ◽

10.3390/antiox10050793 ◽

2021 ◽

Vol 10 (5) ◽

pp. 793

Author(s):

Cheng Schwank-Xu ◽

Elisabete Forsberg ◽

Magnus Bentinger ◽

Allan Zhao ◽

Ishrath Ansurudeen ◽

...

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Mouse Model ◽

Mitochondrial Function ◽

Diabetes Complications ◽

Synergistic Effects ◽

Coenzyme Q ◽

Protective Effects ◽

Beneficial Effects

Mitochondrial dysfunction in type 2 diabetes leads to oxidative stress, which drives disease progression and diabetes complications. L-carnosine, an endogenous dipeptide, improves metabolic control, wound healing and kidney function in animal models of type 2 diabetes. Coenzyme Q (CoQ), a component of the mitochondrial electron transport chain, possesses similar protective effects on diabetes complications. We aimed to study the effect of carnosine on CoQ, and assess any synergistic effects of carnosine and CoQ on improved mitochondrial function in a mouse model of type 2 diabetes. Carnosine enhanced CoQ gene expression and increased hepatic CoQ biosynthesis in db/db mice, a type 2 diabetes model. Co-administration of Carnosine and CoQ improved mitochondrial function, lowered ROS formation and reduced signs of oxidative stress. Our work suggests that carnosine exerts beneficial effects on hepatic CoQ synthesis and when combined with CoQ, improves mitochondrial function and cellular redox balance in the liver of diabetic mice. (4) Conclusions: L-carnosine has beneficial effects on oxidative stress both alone and in combination with CoQ on hepatic mitochondrial function in an obese type 2 diabetes mouse model.

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