Sex Steroid Regulation of Oxidative Stress in Bone Cells: An In Vitro Study

Environmental stimuli, including sex hormones and oxidative stress (OS), affect bone balance, modifying the epigenetic profiles of key osteogenic genes. Nonetheless, the interplay between sex steroids, epigenome and OS has yet be fully elucidated. This paper aims to study in vitro the role of sex steroids in OS-induced alteration in bone cells’ homeostasis, and to assess the possible contribution of epigenetic modifications. Toward this purpose, osteoblast (MC3T3-E1) and osteocyte (MLOY-4) cell lines were exposed to two different sources of free oxygen radicals, i.e., tert-butyl hydroperoxide and dexamethasone, and the protective effect of pre-treatment with androgens and estrogens was evaluated. In particular, we analyzed parameters that reflect bone cell homeostasis such as cell viability, cell migration, transcriptomic profile, transcriptional activity, and epigenetic signature. Our findings indicate that estrogens and androgens counteract OS effects. Using partially overlapping strategies, they reduce OS outcomes regarding cell viability, cell migration, the transcriptomic profile of gene families involved in bone remodeling, and epigenetic profile, i.e., H3K4me3 level. Additionally, we demonstrated that the protective effect of steroids against OS on bone homeostasis is partially mediated by the Akt pathway. Overall, these results suggest that the hormonal milieu may influence the mechanisms of age-related bone disease.

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Inhibitory effects of Panax ginseng glycoproteins in models of doxorubicin-induced cardiac toxicity in vivo and in vitro

Food & Function ◽

10.1039/d1fo01307f ◽

2021 ◽

Author(s):

Yajun Chen ◽

Lei Wang ◽

Tianjia Liu ◽

Zhidong Qiu ◽

Ye Qiu ◽

...

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Cell Viability ◽

Panax Ginseng ◽

Cardiac Toxicity ◽

H9c2 Cell ◽

Inhibitory Effects ◽

Myocardial Oxidative Stress

We investigated the protective effect of PGP against DOX-induced cardiotoxicity in vitro and in vivo. PGP increases H9C2 cell viability and inhibits apoptosis, alleviating DOX-induced myocardial oxidative stress-related cardiotoxicity.

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Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog

Journal of Toxicology ◽

10.1155/2011/109516 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 17

Author(s):

Victor Paromov ◽

Sudha Kumari ◽

Marianne Brannon ◽

Naga S. Kanaparthy ◽

Hongsong Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Cell Viability ◽

Sulfur Mustard ◽

Alkylating Agents ◽

Water Soluble ◽

Model Systems ◽

Mustard Gas

Sulfur mustard or mustard gas (HD) and its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES), or “half-mustard gas,” are alkylating agents that induce DNA damage, oxidative stress, and inflammation. HD/CEES are rapidly absorbed in the skin causing extensive injury. We hypothesize that antioxidant liposomes that deliver both water-soluble and lipid-soluble antioxidants protect skin cells from immediate CEES-induced damage via attenuating oxidative stress. Liposomes containing water-soluble antioxidants and/or lipid-soluble antioxidants were evaluated usingin vitromodel systems. Initially, we found that liposomes containing encapsulated glutathione (GSH-liposomes) increased cell viability and attenuated production of reactive oxygen species (ROS) in HaCaT cells exposed to CEES. Next, GSH-liposomes were tested in a human epidermal model, EpiDerm. In the EpiDerm, GSH-liposomes administered simultaneously or 1 hour after CEES exposure (2.5 mM) increased cell viability, inhibited CEES-induced loss of ATP and attenuated changes in cellular morphology, but did not reduce caspase-3 activity. These findings paralleled the previously describedin vivoprotective effect of antioxidant liposomes in the rat lung and established the effectiveness of GSH-liposomes in a human epidermal model. This study provides a rationale for use of antioxidant liposomes against HD toxicity in the skin considering further verification in animal models exposed to HD.

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Protective Effect of Shikimic Acid against Cisplatin-Induced Renal Injury: In Vitro and In Vivo Studies

Plants ◽

10.3390/plants9121681 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1681

Author(s):

Jinkyung Lee ◽

Quynh Nhu Nguyen ◽

Jun Yeon Park ◽

Sullim Lee ◽

Gwi Seo Hwang ◽

...

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Cell Viability ◽

Renal Injury ◽

Shikimic Acid ◽

Kidney Injury ◽

In Vivo Studies ◽

Artemisia Absinthium ◽

Vitro Assay

Nephrotoxicity is a serious side effect of cisplatin, which is one of the most frequently used drugs for cancer treatment. This study aimed to assess the renoprotective effect of Artemisia absinthium extract and its bioactive compound (shikimic acid) against cisplatin-induced renal injury. An in vitro assay was performed in kidney tubular epithelial cells (LLC-PK1) with 50, 100, and 200 µg/mL A. absinthium extract and 25 and 50 µM shikimic acid, and cytotoxicity was induced by 25 µM cisplatin. BALB/c mice (6 weeks old) were injected with 16 mg/kg cisplatin once and orally administered 25 and 50 mg/kg shikimic acid daily for 4 days. The results showed that the A. absinthium extract reversed the decrease in renal cell viability induced by cisplatin, whereas it decreased the reactive oxidative stress accumulation and apoptosis in LLC-PK1 cells. Shikimic acid also reversed the effect on cell viability but decreased oxidative stress and apoptosis in renal cells compared with the levels in the cisplatin-treated group. Furthermore, shikimic acid protected against kidney injury in cisplatin-treated mice by reducing serum creatinine levels. The protective effect of shikimic acid against cisplatin-mediated kidney injury was confirmed by the recovery of histological kidney injury in cisplatin-treated mice. To the best of our knowledge, this study is the first report on the nephroprotective effect of A. absinthium extract and its mechanism of action against cisplatin-induced renal injury.

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In vitro - studies with antler bone cells: Structure forming capacity, osteocalcin production and influence of sex steroids

Osteologie/Osteology ◽

10.1024/1019-1291.15.4.245 ◽

2006 ◽

Vol 15 (04) ◽

pp. 245-257 ◽

Cited By ~ 3

Author(s):

H. J. Rolf ◽

K. G. Wiese ◽

H. Siggelkow ◽

H. Schliephake ◽

G. A. Bubernik

Keyword(s):

Sex Steroids ◽

Bone Cells ◽

In Vitro Studies ◽

Osteocalcin Production

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CXCR4-targeted Nanoparticles Reduce Cell Viability, Induce Apoptosis and Inhibit SDF-1α Induced BT-549-Luc Cell Migration In Vitro

Current Drug Delivery ◽

10.2174/1567201814666170216130448 ◽

2017 ◽

Vol 14 (8) ◽

Cited By ~ 1

Author(s):

Chuda Chittasupho ◽

Prartana Kewsuwan ◽

Takashi Murakami

Keyword(s):

Cell Migration ◽

Cell Viability ◽

Targeted Nanoparticles ◽

Reduce Cell Viability

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MiR-485-5p Promotes Neuron Survival through Mediating Rac1/Notch2 Signaling Pathway after Cerebral Ischemia/Reperfusion

Current Neurovascular Research ◽

10.2174/1567202617666200415154822 ◽

2020 ◽

Vol 17 (3) ◽

pp. 259-266 ◽

Cited By ~ 2

Author(s):

Xuan Chen ◽

Sumei Zhang ◽

Peipei Shi ◽

Yangli Su ◽

Dong Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Viability ◽

Therapeutic Option ◽

Ischemia Reperfusion ◽

Glucose Deprivation ◽

Small Gtpase ◽

Luciferase Reporter ◽

Pathological Feature ◽

In Cells

Objective: Ischemia-reperfusion (I/R) injury is a pathological feature of ischemic stroke. This study investigated the regulatory role of miR-485-5p in I/R injury. Methods: SH-SY5Y cells were induced with oxygen and glucose deprivation/reoxygenation (OGD/R) to mimic I/R injury in vitro. Cells were transfected with designated constructs (miR-485- 5p mimics, miR-485-5p inhibitor, lentiviral vectors overexpressing Rac1 or their corresponding controls). Cell viability was evaluated using the MTT assay. The concentrations of lactate dehydrogenase, malondialdehyde, and reactive oxygen species were detected to indicate the degree of oxidative stress. Flow cytometry and caspase-3 activity assay were used for apoptosis assessment. Dual-luciferase reporter assay was performed to confirm that Rac family small GTPase 1 (Rac1) was a downstream gene of miR-485-5p. Results: OGD/R resulted in decreased cell viability, elevated oxidative stress, increased apoptosis, and downregulated miR-485-5p expression in SH-SY5Y cells. MiR-485-5p upregulation alleviated I/R injury, evidenced by improved cell viability, decreased oxidative markers, and reduced apoptotic rate. OGD/R increased the levels of Rac1 and neurogenic locus notch homolog protein 2 (Notch2) signaling-related proteins in cells with normal miR-485-5p expression, whereas miR- 485-5p overexpression successfully suppressed OGD/R-induced upregulation of these proteins. Furthermore, the delivery of vectors overexpressing Rac1 in miR-485-5p mimics-transfected cells reversed the protective effect of miR-485-5p in cells with OGD/R-induced injury. Conclusion: This study showed that miR-485-5p protected cells following I/R injury via targeting Rac1/Notch2 signaling suggest that targeted upregulation of miR-485-5p might be a promising therapeutic option for the protection against I/R injury.

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Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models In Vivo and In Vitro

Molecules ◽

10.3390/molecules26082204 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2204

Author(s):

Meng-Die Yang ◽

Yang Sun ◽

Wen-Jun Zhou ◽

Xiao-Zheng Xie ◽

Qian-Mei Zhou ◽

...

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Tumor Growth ◽

Cell Viability ◽

Synergistic Effects ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Tgf Β1

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

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Protective effect of vitamin C and lycopene on the in vitro fertilization capacity of sex‐sorted bull sperm by inhibiting the oxidative stress

Reproduction in Domestic Animals ◽

10.1111/rda.13748 ◽

2020 ◽

Vol 55 (9) ◽

pp. 1103-1114

Author(s):

Pei‐Pei Zhang ◽

Jing‐Jing Wang ◽

Chong‐Yang Li ◽

Hai‐sheng Hao ◽

Hao‐Yu Wang ◽

...

Keyword(s):

Oxidative Stress ◽

In Vitro Fertilization ◽

Vitamin C ◽

Protective Effect ◽

Vitro Fertilization ◽

Bull Sperm ◽

Fertilization Capacity

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miR-187 modulates cardiomyocyte apoptosis and oxidative stress in myocardial infarction mice via negatively regulating DYRK2

10.22514/sv.2021.137 ◽

2021 ◽

Keyword(s):

Oxidative Stress ◽

Myocardial Infarction ◽

Protective Effect ◽

Myocardial Infarct ◽

Annexin V ◽

Cardiomyocyte Apoptosis ◽

Ros Generation ◽

Downstream Target

Myocardial infarction is a serious representation of cardiovescular disease, MicroRNAs play a role in modifying I/R injury and myocardial infarct remodeling. The present study therefore examined the potential role of miR-187 in cardiac I/R injury and its underlying mechanisms. miR-187 was inhibited or overexpressed in cardiomyocytes H/R models by pretreatment with miR-187 mimic or inhibitor to confirm the function of miR-187 in H/R. DYRK2 was inhibited or overexpressed in cardiomyocytes H/R models by pretreatment with DYRK2 inhibitor. A myocardium I/R mouse model was established. Circulating levels of miR-187 or DYRK2 was detected by quantitative realtime PCR and protein expression was detected by western blotting. The cell viability in all groups was determined by MTT assay and the apoptosis ratio was detected by flow cytometry after staining with Annexin V-FITC. The effect of miR-187 on cellular ROS generation was examined by DCFH-DA. The level of lipid peroxidation and SOD expression were determined by MDA and SOD assay. The findings indicated that miR-187 may be a possible regulator in the protective effect of H/R-induced cardiomyocyte apoptosis, cellular oxidative stress and leaded to DYRK2 suppression at a posttranscriptional level. Moreover, the improvement of miR-187 on H/R-induced cardiomyocyte injury contributed to the obstruction of DYRK2 expression. In addition, these results identified DYRK2 as the functional downstream target of miR-187 regulated myocardial infarction and oxidative stress.These present work provided the first insight into the function of miR-187 in successfully protect cardiomyocyte both in vivo and in vitro, and such a protective effect were mediated through the regulation of DYRK2 expression.

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