scholarly journals Xinmailong Attenuates Doxorubicin-Induced Lysosomal Dysfunction and Oxidative Stress in H9c2 Cells via HO-1

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yu Jiang ◽  
Yanjuan Liu ◽  
Wen Xiao ◽  
Dandan Zhang ◽  
Xiehong Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Injury ◽  
Specific Inhibitor ◽  
Heme Oxygenase 1 ◽  
H9c2 Cells ◽  
Autophagy Flux ◽  
Sod Activity ◽  
Lysosomal Function ◽  
Lysosomal Dysfunction ◽  
And Oxidative Stress

The clinical use of doxorubicin (DOX) is limited by its cardiotoxicity, which is closely associated with oxidative stress. Xinmailong (XML) is a bioactive peptide extracted from American cockroaches, which has been mainly applied to treat chronic heart failure in China. Our previous study showed that XML attenuates DOX-induced oxidative stress. However, the mechanism of XML in DOX-induced cardiotoxicity remains unclear. Heme oxygenase-1 (HO-1), an enzyme that is ubiquitously expressed in all cell types, has been found to take antioxidant effects in many cardiovascular diseases, and its expression is protectively upregulated under DOX treatment. Lysosome and autophagy are closely involved in oxidative stress as well. It is still unknown whether XML could attenuate doxorubicin-induced lysosomal dysfunction and oxidative stress in H9c2 cells via HO-1. Thus, this study was aimed at investigating the involvement of HO-1-mediated lysosomal function and autophagy flux in DOX-induced oxidative stress and cardiotoxicity in H9c2 cells. Our results showed that XML treatment markedly increased cell proliferation and SOD activity, improved lysosomal function, and ameliorated autophagy flux block in DOX-treated H9c2 cells. Furthermore, XML significantly increased HO-1 expression following DOX treatment. Importantly, HO-1-specific inhibitor (Znpp) or HO-1 siRNA could significantly attenuate the protective effects of XML against DOX-induced cell injury, oxidative stress, lysosomal dysfunction, and autophagy flux block. These results suggest that XML protects against DOX-induced cardiotoxicity through HO-1-mediated recovery of lysosomal function and autophagy flux and decreases oxidative stress, providing a novel mechanism responsible for the protection of XML against DOX-induced cardiomyopathy.

scholarly journals Anshen Buxin Liuwei Pill, a Mongolian Medicinal Formula, Could Protect H2O2-Induced H9c2 Myocardial Cell Injury by Suppressing Apoptosis, Calcium Channel Activation, and Oxidative Stress

2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Yue Dong ◽  
Hai-Ying Tong ◽  
Xian-Ju Huang ◽  
Ghulam Murtaza ◽  
Yu-Jia Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Injury ◽  
Cardiac Injury ◽  
Myocardial Cell ◽  
H9c2 Cell ◽  
Mrna Levels ◽  
H9c2 Cells ◽  
Therapeutic Benefits ◽  
Myocardial Cell Injury ◽  
And Oxidative Stress

Background. Anshen Buxin Liuwei pill (ABLP) is a Mongolian medicinal formula which has a therapeutic effect on the symptoms such as coronary heart disease, angina pectoris, arrhythmia, depression and irritability, palpitation, and short breath. However, its bioactivity against cardiac injury remains unclear. Methods. The protective effect of ABLP was evaluated using H9c2 cells. Cell viability, intracellular Ca2+, reactive oxidative indices, and mitochondrial membrane potential (∆ψ) were assessed, respectively. The mRNA levels of Ca2+ channel-related genes (DHPR, RyR2, and SCN5A) and oxidative stress-related genes (Keap1, Nrf2, and HO-1) were measured by RT-PCR. Results. 0.5–50 μg/mL ABLP could significantly decrease H2O2-induced cell injury by suppressing cell necrosis/apoptosis and excess oxidative stress, ameliorating the collapse of ∆ψ, and reducing intracellular Ca2+ concentration. Furthermore, 0.5–50 μg/mL ABLP reversed H2O2-induced imbalance in the mRNA levels of DHPR, RyR2, SCN5A, Keap1, Nrf2, and HO-1 gene in H9c2 cells, which further illustrate the mechanism. Conclusion. ABLP provided protective and therapeutic benefits against H2O2-induced H9c2 cell injury, indicating that this formula can effectively treat coronary disease. In addition, the present study also provides an in-depth understanding of the pharmacological functions of ABLP, which may lead to further successful applications of Mongolian medicine.

scholarly journals Scutellarin attenuates hypoxia/reoxygenation injury in hepatocytes by inhibiting apoptosis and oxidative stress through regulating Keap1/Nrf2/ARE signaling

2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Haiyuan Wu ◽  
Lan Jia
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion ◽  
Heme Oxygenase 1 ◽  
Oxygen Species ◽  
Protective Effects ◽  
Sod Activity ◽  
Reoxygenation Injury ◽  
Nrf2 Expression ◽  
And Oxidative Stress ◽  
Hypoxia Reoxygenation

Abstract Scutellarin is a natural flavonoid that has been found to exhibit anti-ischemic effect. However, the effect of scutellarin on hepatic hypoxia/reoxygenation (ischemia–reperfusion (I/R)) injury remains unknown. The aim of the present study was to explore the protective effect of scutellarin on I/R-induced injury in hepatocytes. Our results showed that scutellarin improved cell viability in hepatocytes exposed to hypoxia/reoxygenation (H/R). Scutellarin treatment resulted in decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased superoxide dismutase (SOD) activity in H/R-induced hepatocytes. In addition, scutellarin reduced cell apoptosis in H/R-stimulated hepatocytes, as proved by the decreased apoptotic rate. Moreover, scutellarin significantly up-regulated bcl-2 expression and down-regulated bax expression in hepatocytes exposed to H/R. Furthermore, scutellarin treatment caused significant decrease in Keap1 expression and increase in nuclear Nrf2 expression. Besides, scutellarin induced the mRNA expressions of heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). Inhibition of Nrf2 significantly reversed the protective effects of scutellarin on H/R-stimulated hepatocytes. In conclusion, these findings demonstrated that scutellarin protected hepatocytes from H/R-induced oxidative injury through regulating the Keap1/Nrf2/ARE signaling pathway, indicating a potential relevance of scutellarin in attenuating hepatic I/R injury.

scholarly journals Chloroquine may induce endothelial injury through lysosomal dysfunction and oxidative stress

2021 ◽  
Vol 414 ◽  
pp. 115412 ◽  
Author(s):  
PauloC. Gregório ◽  
Regiane S. da Cunha ◽  
Gilson Biagini ◽  
Bruna Bosquetti ◽  
Júlia Budag ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Injury ◽  
Lysosomal Dysfunction ◽  
And Oxidative Stress

Daphnetin Ameliorates Corticosterone-Induced Depressive-Like Behavior and Oxidative Stress in Mice Via Nuclear Factor Erythroid 2-Related Factor/Heme Oxygenase-1 Pathway

2021 ◽  
Vol 19 (4) ◽  
pp. 470-476
Author(s):  
Chao Liu ◽  
Chao Liang ◽  
Jie Huang
Keyword(s):  
Oxidative Stress ◽  
Consumption Rate ◽  
Tail Suspension Test ◽  
Protein Carbonyl ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Sucrose Consumption ◽  
Markers Of Oxidative Stress ◽  
Swimming Test ◽  
And Oxidative Stress

We have investigated the effect of daphnetin on depressive-like behavior and oxidative stress caused by corticosterone in mice. To this end, we have analyzed the effect of corticosterone alone and combination of corticosterone and daphnetin on three behavioral indices of depressive-like behavior - sucrose consumption rate, forced swimming test, and tail suspension test as well as biochemical markers of oxidative stress - malondialdehyde, nitrite, protein carbonyl, nonprotein sulfhydryl and glutathione contents as well as hippocampal cell apoptosis. The results support the conclusion that daphnetin diminished corticosterone induced depressive like behavior and oxidative stress by activating Nrf2/HO-1 pathway.

CTRP3 protects against uric acid-induced endothelial injury by inhibiting inflammation and oxidase stress in rats

2021 ◽  
pp. 153537022110471
Author(s):  
Junxia Zhang ◽  
Xue Lin ◽  
Jinxiu Xu ◽  
Feng Tang ◽  
Lupin Tan
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Inflammatory Responses ◽  
Umbilical Vein ◽  
Specific Inhibitor ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Sprague Dawley ◽  
Protein Levels ◽  
And Oxidative Stress

Hyperuricemia, which contributes to vascular endothelial damage, plays a key role in multiple cardiovascular diseases. This study was designed to investigate whether C1q/tumor necrosis factor (TNF)-related protein 3 (CTRP3) has a protective effect on endothelial damage induced by uric acid and its underlying mechanisms. Animal models of hyperuricemia were established in Sprague-Dawley (SD) rats through the consumption of 10% fructose water for 12 weeks. Then, the rats were given a single injection of Ad-CTRP3 or Ad-GFP. The animal experiments were ended two weeks later. In vitro, human umbilical vein endothelial cells (HUVECs) were first infected with Ad-CTRP3 or Ad-GFP. Then, the cells were stimulated with 10 mg/dL uric acid for 48 h after pretreatment with or without a Toll-like receptor 4 (TLR4)-specific inhibitor. Hyperuricemic rats showed disorganized intimal structures, increased endothelial apoptosis rates, increased inflammatory responses and oxidative stress, which were accompanied by reduced CTRP3 and elevated TLR4 protein levels in the thoracic aorta. In contrast, CTRP3 overexpression decreased TLR4 protein levels and ameliorated inflammatory responses and oxidative stress, thereby improving the morphology and apoptosis of the aortic endothelium in rats with hyperuricemia. Similarly, CTRP3 overexpression decreased TLR4-mediated inflammation, reduced oxidative stress, and rescued endothelial damage induced by uric acid in HUVECs. In conclusion, CTRP3 ameliorates uric acid-induced inflammation and oxidative stress, which in turn protects against endothelial injury, possibly by inhibiting TLR4-mediated inflammation and downregulating oxidative stress.

scholarly journals Kaempferol and Kaempferide Attenuate Oleic Acid-Induced Lipid Accumulation and Oxidative Stress in HepG2 Cells

2021 ◽  
Vol 22 (16) ◽  
pp. 8847
Author(s):  
Fangfang Tie ◽  
Jin Ding ◽  
Na Hu ◽  
Qi Dong ◽  
Zhi Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oleic Acid ◽  
Lipid Metabolism ◽  
Western Blot ◽  
Blot Analysis ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Western Blot Analysis ◽  
Heme Oxygenase 1 ◽  
And Oxidative Stress

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases which lacks ideal treatment options. Kaempferol and kaempferide, two natural flavonol compounds isolated from Hippophae rhamnoides L., were reported to exhibit a strong regulatory effect on lipid metabolism, for which the mechanism is largely unknown. In the present study, we investigated the effects of kaempferol and kaempferide on oleic acid (OA)-treated HepG2 cells, a widely used in vitro model of NAFLD. The results indicated an increased accumulation of lipid droplets and triacylglycerol (TG) by OA, which was attenuated by kaempferol and kaempferide (5, 10 and 20 μM). Western blot analysis demonstrated that kaempferol and kaempferide reduced expression of lipogenesis-related proteins, including sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD-1). Expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer binding proteins β (C/EBPβ), two adipogenic transcription factors, was also decreased by kaempferol and kaempferide treatment. In addition, western blot analysis also demonstrated that kaempferol and kaempferide reduced expression of heme oxygenase-1 (HO-1) and nuclear transcription factor-erythroid 2-related factor 2 (Nrf2). Molecular docking was performed to identify the direct molecular targets of kaempferol and kaempferide, and their binding to SCD-1, a critical regulator in lipid metabolism, was revealed. Taken together, our findings demonstrate that kaempferol and kaempferide could attenuate OA-induced lipid accumulation and oxidative stress in HepG2 cells, which might benefit the treatment of NAFLD.

scholarly journals CARDIOPROTECTIVE POTENTIAL OF QUERCETIN AGAINST DIESEL OR PETROL EXHAUST NANOPARTICLE INDUCED TOXICITY: A PROSPECTIVE IN VITRO PHARMACOLOGICAL STUDY IN H9C2 CELLS

2021 ◽  
pp. 139-144
Author(s):  
MOHAN DURGA ◽  
THIYAGARAJAN DEVASENA
Keyword(s):  
Oxidative Stress ◽  
Diesel Exhaust ◽  
Pharmacological Study ◽  
Lethal Effect ◽  
Protective Role ◽  
Cardiac Cells ◽  
H9c2 Cells ◽  
Sod Activity ◽  
Cardioprotective Effects

Objective: Phytochemicals are known to elicit potential antioxidant activity. This study examined the cardioprotective effects of quercetin against oxidative damage to rat cardiomyocyte cells (H9c2) after treatment with Diesel Exhaust Nanoparticles (DEPs) or Petrol Exhaust Nanoparticles (PEPs). Methods: Cardiomyocyte cells were exposed to DEPs or PEPs alone and in a combination with quercetin for 24 h. Results: Results showed that quercetin had no lethal effect on H9c2 cells up to a concentration of 1.0 μg/ml. Exposure to DEPs (4.0 μg/ml) or PEPs (10.0 μg/ml) induced cytotoxicity, oxidative stress, and inflammation (p<0.05). It also provoked lipid peroxidation by an increase in MDA and a decrease in SOD activity and glutathione activity (p<0.05). Simultaneous addition of quercetin restored these parameters to near normal. Conclusion: These results thus specify that quercetin plays a protective role in cardiac cells exposed to DEPs and PEPs.

scholarly journals IL-23 Promotes Myocardial I/R Injury by Increasing the Inflammatory Responses and Oxidative Stress Reactions

2016 ◽  
Vol 38 (6) ◽  
pp. 2163-2172 ◽  
Author(s):  
Xiaorong Hu ◽  
Ruisong Ma ◽  
Jiajia Lu ◽  
Kai Zhang ◽  
Weipan Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Tunel Staining ◽  
Ischemia And Reperfusion ◽  
Stress Reactions ◽  
Sprague Dawley ◽  
Sod Activity ◽  
Myocardial Ischemia And Reperfusion ◽  
Tnf Α ◽  
And Oxidative Stress

Background/Aims: Inflammation and oxidative stress play an important role in myocardial ischemia and reperfusion (I/R) injury. We hypothesized that IL-23, a pro-inflammatory cytokine, could promote myocardial I/R injury by increasing the inflammatory response and oxidative stress. Methods: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO) group, ischemia and reperfusion (I/R) group, (IL-23 + I/R) group and (anti-IL-23 + I/R) group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH), creatine kinase (CK) and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-α and IL-6 were detected by Elisa. Results: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK (all P < 0.05). Meanwhile, IL-23 significantly increased the expression of eIL-17A, TNF-α and IL-6 and enhanced both the increase of the MDA level and the decrease of the SOD level induced by I/R (all P<0.05). IL-23 had no effect on the expression of HMGB1 (p > 0.05). All these effects were abolished by anti-IL-23 administration. Conclusion: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction.

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