Interleukin‐9 deficiency affects lipopolysaccharide‐induced macrophage‐related oxidative stress and myocardial cell apoptosis via the Nrf2 pathway both in vivo and in vitro

BioFactors ◽  
2021 ◽  
Author(s):  
Zhishan Liang ◽  
Fuze Pan ◽  
Zicong Yang ◽  
Mengjie Wang ◽  
Changxing Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Myocardial Cell ◽  
Nrf2 Pathway ◽  
Interleukin 9

scholarly journals Aspirin Eugenol Ester Protects Vascular Endothelium From Oxidative Injury by the Apoptosis Signal Regulating Kinase-1 Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Mei-Zhou Huang ◽  
Zhen-Dong Zhang ◽  
Ya-Jun Yang ◽  
Xi-Wang Liu ◽  
Zhe Qin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vascular Endothelium ◽  
Cell Apoptosis ◽  
Oxidative Injury ◽  
Vital Role ◽  
Stress Effect ◽  
Antioxidative Stress ◽  
Aspirin Eugenol Ester

Aspirin eugenol ester (AEE) is a new potential pharmaceutical compound possessing anti-inflammatory, anti-cardiovascular disease, and antioxidative stress activity. The pharmacological activities of AEE are partly dependent on its regulation of cell apoptosis. However, it is still unclear how AEE inhibits cell apoptosis on the basis of its antioxidative stress effect. This study aimed to reveal the vascular antioxidative mechanism of AEE in response to H2O2-induced oxidative stress in HUVECs and paraquat-induced oxidative stress in rats. In the different intervention groups of HUVECs and rats, the expression of ASK1, ERK1/2, SAPK/JNK, and p38 and the phosphorylation levels of ERK1/2, SAPK/JNK, and p38 were measured. The effects of ASK1 and ERK1/2 on the anti-apoptotic activity of AEE in the oxidative stress model were probed using the corresponding inhibitors ASK1 and ERK1/2. The results showed that in the HUVECs, 200 μM H2O2 treatment significantly increased the phosphorylation of SAPK/JNK and the level of ASK1 but decreased the phosphorylation of ERK1/2, while in the HUVECs pretreated with AEE, the H2O2-induced changes were significantly ameliorated. The findings were observed in vitro and in vivo. Moreover, inhibition of ASK1 and ERK1/2 showed that ASK1 plays a vital role in the protective effect of AEE on H2O2-induced apoptosis. All findings suggested that AEE protects the vascular endothelium from oxidative injury by mediating the ASK1 pathway.

scholarly journals Graphene Oxide and Reduced Graphene Oxide Exhibit Cardiotoxicity Through the Regulation of Lipid Peroxidation, Oxidative Stress, and Mitochondrial Dysfunction

2021 ◽  
Vol 9 ◽  
Author(s):  
Jian Zhang ◽  
Hong-Yan Cao ◽  
Ji-Qun Wang ◽  
Guo-Dong Wu ◽  
Lin Wang
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Graphene Oxide ◽  
Membrane Potential ◽  
Gamma Irradiation ◽  
Cell Apoptosis ◽  
Mitochondrial Membrane ◽  
H9c2 Cells

ObjectiveGraphene has been widely used for various biological and biomedical applications due to its unique physiochemical properties. This study aimed to evaluate the cardiotoxicity of graphene oxide (GO) and reduced GO (rGO) in vitro and in vivo, as well as to investigate the underlying toxicity mechanisms.MethodsGO was reduced by gamma irradiation to prepare rGO and then characterized by UV/visible light absorption spectroscopy. Rat myocardial cells (H9C2) were exposed to GO or rGO with different absorbed radiation doses. The in vitro cytotoxicity was evaluated by MTT assay, cell apoptosis assay, and lactate dehydrogenase (LDH) activity assay. The effects of GO and rGO on oxidative damage and mitochondrial membrane potential were also explored in H9C2 cells. For in vivo experiments, mice were injected with GO or rGO. The histopathological changes of heart tissues, as well as myocardial enzyme activity and lipid peroxidation indicators in heart tissues were further investigated.ResultsrGO was developed from GO following different doses of gamma irradiation. In vitro experiments in H9C2 cells showed that compared with control cells, both GO and rGO treatment inhibited cell viability, promoted cell apoptosis, and elevated the LDH release. With the increasing radiation absorbed dose, the cytotoxicity of rGO gradually increased. Notably, GO or rGO treatment increased the content of ROS and reduced the mitochondrial membrane potential in H9C2 cells. In vivo experiments also revealed that GO or rGO treatment damaged the myocardial tissues and changed the activities of several myocardial enzymes and the lipid peroxidation indicators in the myocardial tissues.ConclusionGO exhibited a lower cardiotoxicity than rGO due to the structure difference, and the cardiotoxicity of GO and rGO might be mediated by lipid peroxidation, oxidative stress, and mitochondrial dysfunction.

The Association of Neuronal Stress with Activating Transcription Factor 3 in Dorsal Root Ganglion of in vivo and in vitro Models of Bortezomib- Induced Neuropathy

2018 ◽  
Vol 19 (1) ◽  
pp. 50-64 ◽  
Author(s):  
Yiting Yin ◽  
Xin Qi ◽  
Yuan Qiao ◽  
Huaxiang Liu ◽  
Zihan Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Cell Apoptosis ◽  
Activating Transcription Factor 3 ◽  
Drg Neurons ◽  
Activating Transcription Factor ◽  
Intracellular Oxidative Stress

Background: The notion that proteasome inhibitor bortezomib (BTZ) induced intracellular oxidative stress resulting in peripheral neuropathy has been generally accepted. The association of mitochondrial dysfunction, cell apoptosis, and endoplasmic reticulum (ER) stress with intracellular oxidative stress is ambiguous and still needs to be investigated. The activation of activating transcription factor 3 (ATF3) is a stress-hub gene which was upregulated in dorsal root ganglion (DRG) neurons after different kinds of peripheral nerve injuries. Objective: To investigate a mechanism underlying the action of BTZ-induced intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress via activation of ATF3. </P><P> Methods: Primary cultured DRG neurons with BTZ induced neurotoxicity and DRG from BTZ induced painful peripheral neuropathic rats were used to approach these questions. Results: BTZ administration caused the upregulation of ATF3 paralleled with intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress in DRG neurons both in vitro and in vivo. Blocking ATF3 signaling by small interfering RNA (siRNA) gene silencing technology resulted in decreased intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress in DRG neurons after BTZ treatment. This study exhibited important mechanistic insight into how BTZ induces neurotoxicity through the activation of ATF3 resulting in intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress and provided a novel potential therapeutic target by blocking ATF3 signaling.

scholarly journals Ethyl Vanillin Protects against Kidney Injury in Diabetic Nephropathy by Inhibiting Oxidative Stress and Apoptosis

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yuna Tong ◽  
Shan Liu ◽  
Rong Gong ◽  
Lei Zhong ◽  
Xingmei Duan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Cell Apoptosis ◽  
Cell Model ◽  
Critical Role ◽  
Kidney Injury ◽  
Related Factor ◽  
Ethyl Vanillin

Diabetes-induced oxidative stress and apoptosis is regarded as a critical role in the pathogenesis of diabetic nephropathy (DN). Treating diabetes-induced kidney damage and renal dysfunction has been thought a promising therapeutic option to attenuate the development and progression of DN. In this study, we investigated the renoprotective effect of ethyl vanillin (EVA), an active analogue of vanillin isolated from vanilla beans, on streptozotocin- (STZ-) induced rat renal injury model and high glucose-induced NRK-52E cell model. The EVA treatment could strongly improve the deterioration of renal function and kidney cell apoptosis in vivo and in vitro. Moreover, treating with EVA significantly decreased the level of MDA and reactive oxygen species (ROS) and stabilized antioxidant enzyme system in response to oxidative stress by enhancing the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in vivo and in vitro. Furthermore, EVA also markedly suppressed cleaved caspase-3, Bax, and nuclear transcription factor erythroid 2-related factor (Nrf2) expression in STZ-induced rats. Therefore, these results of our investigation provided that EVA might protect against kidney injury in DN by inhibiting oxidative stress and cell apoptosis.

CYT-Rx20 inhibits ovarian cancer cells in vitro and in vivo through oxidative stress-induced DNA damage and cell apoptosis

2017 ◽  
Vol 79 (6) ◽  
pp. 1129-1140 ◽  
Author(s):  
Yen-Yun Wang ◽  
Yuk-Kwan Chen ◽  
Stephen Chu-Sung Hu ◽  
Ya-Ling Hsu ◽  
Chun-Hao Tsai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ovarian Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Ovarian Cancer Cells

scholarly journals Molecules from American Ginseng Suppress Colitis through Nuclear Factor Erythroid-2-Related Factor 2

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1850
Author(s):  
Anusha Chaparala ◽  
Hossam Tashkandi ◽  
Alexander A. Chumanevich ◽  
Erin E. Witalison ◽  
Anthony Windust ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
American Ginseng ◽  
Chronic Inflammatory Bowel Disease ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Pathway ◽  
Nrf2 Knockout ◽  
Inflammatory Bowel

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects millions of people worldwide and increases the risk of colorectal cancer (CRC) development. We have previously shown that American ginseng (AG) can treat colitis and prevent colon cancer in mice. We further fractionated AG and identified the most potent fraction, hexane fraction (HAG), and the most potent compound in this fraction, panaxynol (PA). Because (1) oxidative stress plays a significant role in the pathogenesis of colitis and associated CRC and (2) nuclear factor erythroid-2-related factor 2 (Nrf2) is the master regulator of antioxidant responses, we examined the role of Nrf2 as a mechanism by which AG suppresses colitis. Through a series of in vitro and in vivo Nrf2 knockout mouse experiments, we found that AG and its components activate the Nrf2 pathway and decrease the oxidative stress in macrophages (mΦ) and colon epithelial cells in vitro. Consistent with these in vitro results, the Nrf2 pathway is activated by AG and its components in vivo, and Nrf2-/- mice are resistant to the suppressive effects of AG, HAG and PA on colitis. Results from this study establish Nrf2 as a mediator of AG and its components in the treatment of colitis.

Taxifolin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of oxidative stress and cell apoptosis

2014 ◽  
Vol 63 ◽  
pp. 221-232 ◽  
Author(s):  
Xiao Sun ◽  
Rong-chang Chen ◽  
Zhi-hong Yang ◽  
Gui-bo Sun ◽  
Min Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Cell Apoptosis

scholarly journals A Protein from Dioscorea polystachya (Chinese Yam) Improves Hydrocortisone-Induced Testicular Dysfunction by Alleviating Leydig Cell Injury via Upregulation of the Nrf2 Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Shiting Yu ◽  
Bing Han ◽  
Xin Xing ◽  
Yixuan Li ◽  
Daqing Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Injury ◽  
Nrf2 Pathway ◽  
Chinese Yam ◽  
Testicular Dysfunction ◽  
Tgf Β1

Leydig cell injury has been described as a primary driver of testicular dysfunction and is affected by oxidative stress. Dioscorea polystachya (Chinese yam) is used to improve testicular dysfunction in clinical and pharmacological research via its antioxidative activity, but the mechanisms underlying the beneficial effect of Chinese yam on testicular dysfunction and its suppression of Leydig cell oxidative damage remain unclear. In this study, we obtained a Chinese yam protein (DP1) and explored its effectiveness and possible mechanism in improving testicular dysfunction in vivo and in vitro. We established a testicular dysfunction model in rats using hydrocortisone (HCT). DP1 increased body weight and organ index, improved the deterioration in testicular morphology (including increasing the diameter of seminiferous tubules and thickness of germinal cell layers, inhibiting testicular cell apoptosis by increasing the Bcl-2/Bax ratio, and impeding collagen leakage by downregulating TGF-β1 and p-SMAD2/3 expression), and restored the testosterone content. In addition, DP1 enhanced the number of Leydig cells in rats and H2O2-induced TM3 Leydig cells, and the effect of DP1 on the apoptosis, fibrosis, and testosterone content of TM3 cells was similar to that observed in vivo. These changes were dependent on the regulation of oxidative stress, including significantly reduced intracellular 8-hydroxy-2-deoxyguanosine levels, enhanced superoxide dismutase activities, and decreased superoxide anion levels, which were confirmed via a superoxide overexpression system. Furthermore, we observed that DP1 promoted Nrf2 nuclear import and upregulated antioxidant factor expression in vivo and in vitro. However, Nrf2 silencing eliminated the ability of DP1 to increase the Bcl-2/Bax ratio, reduce the expression levels of TGF-β1 and p-SMAD2/3, and increase testosterone contents in H2O2-induced TM3 cells. In conclusion, DP1 reversed the HCT-induced testicular apoptosis and fibrosis and decreased testosterone contents by alleviating Leydig cell oxidative damage via upregulation of the Nrf2 pathway.

scholarly journals Metformin prevents methylglyoxal-induced apoptosis by suppressing oxidative stress in vitro and in vivo

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Gang Wang ◽  
Yanan Wang ◽  
Qinzhi Yang ◽  
Chunrong Xu ◽  
Youkun Zheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Vascular Complications ◽  
Tunel Staining ◽  
Ros Generation ◽  
Dependent Manner ◽  
Diabetic Vascular Complications ◽  
Induced Apoptosis

AbstractMethylglyoxal (MGO) is an active metabolite of glucose and plays a prominent role in the pathogenesis of diabetic vascular complications, including endothelial cell apoptosis induced by oxidative stress. Metformin (MET), a widely prescribed antidiabetic agent, appears to reduce excessive reactive oxygen species (ROS) generation and limit cell apoptosis. However, the molecular mechanisms underlying this process are still not fully elucidated. We reported here that MET prevents MGO-induced apoptosis by suppressing oxidative stress in vitro and in vivo. Protein expression and protein phosphorylation were investigated using western blotting, ELISA, and immunohistochemical staining, respectively. Cell viability and apoptosis were assessed by the MTT assay, TUNEL staining, and Annexin V-FITC and propidium iodide double staining. ROS generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. Our results revealed that MET prevented MGO-induced HUVEC apoptosis, inhibited apoptosis-associated biochemical changes such as loss of MMP, the elevation of the Bax/Bcl-2 ratio, and activation of cleaved caspase-3, and attenuated MGO-induced mitochondrial morphological alterations in a dose-dependent manner. MET pretreatment also significantly suppressed MGO-stimulated ROS production, increased signaling through the ROS-mediated PI3K/Akt and Nrf2/HO-1 pathways, and markedly elevated the levels of its downstream antioxidants. Finally, similar results were obtained in vivo, and we demonstrated that MET prevented MGO-induced oxidative damage, apoptosis, and inflammation. As expected, MET reversed MGO-induced downregulation of Nrf2 and p-Akt. In addition, a PI3K inhibitor (LY-294002) and a Nrf2 inhibitor (ML385) observably attenuated the protective effects of MET on MGO-induced apoptosis and ROS generation by inhibiting the Nrf2/HO-1 pathways, while a ROS scavenger (NAC) and a permeability transition pores inhibitor (CsA) completely reversed these effects. Collectively, these findings broaden our understanding of the mechanism by which MET regulates apoptosis induced by MGO under oxidative stress conditions, with important implications regarding the potential application of MET for the treatment of diabetic vascular complications.

scholarly journals Arctiin Antagonizes Triptolide-Induced Hepatotoxicity via Activation of Nrf2 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yuyan Zhou ◽  
Li Xia ◽  
Weiqiang Yao ◽  
Jun Han ◽  
Guodong Wang
Keyword(s):  
Oxidative Stress ◽  
Protective Role ◽  
Protective Agent ◽  
In Vivo Models ◽  
Nrf2 Pathway ◽  
Tripterygium Wilfordii Hook F ◽  
Oxidative Stress Pathway ◽  
Tripterygium Wilfordii Hook

Triptolide (TP) is the most effective ingredient found in the traditional Chinese herbal Tripterygium wilfordii Hook F, and it is widely used in therapies of autoimmune and inflammatory disorders. However, the hepatotoxicity induced by TP has restricted its use in clinical trials. Arctiin is known as a protective agent against oxidative stress, and it exerts liver-protecting effect. This study was aimed at investigating the protective role of arctiin against TP-induced hepatotoxicity using in vitro and in vivo models. The results indicated that TP not only obviously induced liver injury in mice but also significantly inhibited the growth of HepG2 cells and increased the level of intracellular reactive oxygen. Furthermore, TP obviously decreased the expressions of proteins of Nrf2 pathway including HO-1, NQO1, and Nrf2 associated with oxidative stress pathway. However, the above experimental indexes were reversed by the treatment of arctiin. Our results suggested that arctiin could alleviate TP-induced hepatotoxicity, and the molecular mechanism is likely related to its capacity against oxidative stress.

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