scholarly journals Vanillin Prevents Doxorubicin-Induced Apoptosis and Oxidative Stress in Rat H9c2 Cardiomyocytes

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2317 ◽  
Author(s):  
Ivana Sirangelo ◽  
Luigi Sapio ◽  
Angela Ragone ◽  
Silvio Naviglio ◽  
Clara Iannuzzi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Point Of View ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Erk Phosphorylation ◽  
H9c2 Cardiomyocytes ◽  
Induced Apoptosis ◽  
Tumor Types

Doxorubicin (doxo) is an effective anticancer compound in several tumor types. However, as a consequence of oxidative stress induction and ROS overproduction, its high cardiotoxicity demands urgent attention. Vanillin possesses antioxidant, antiproliferative, antidepressant and anti-glycating properties. Therefore, we investigated the potential vanillin protective effects against doxo-induced cardiotoxicity in H9c2 cells. Using multiparametric approach, we demonstrated that vanillin restored both cell viability and damage in response to doxo exposure. Contextually, vanillin decreased sub-G1 appearance and caspase-3 and PARP1 activation, reducing the doxo-related apoptosis induction. From a mechanistic point of view, vanillin hindered doxo-induced ROS accumulation and impaired the ERK phosphorylation. Notably, besides the cardioprotective effects, vanillin did not counteract the doxo effectiveness in osteosarcoma cells. Taken together, our results suggest that vanillin ameliorates doxo-induced toxicity in H9c2 cells, opening new avenues for developing alternative therapeutic approaches to prevent the anthracycline-related cardiotoxicity and to improve the long-term outcome of antineoplastic treatment.

scholarly journals Lingonberry anthocyanins protect cardiac cells from oxidative-stress-induced apoptosis

2017 ◽  
Vol 95 (8) ◽  
pp. 904-910 ◽  
Author(s):  
Cara K. Isaak ◽  
Jay C. Petkau ◽  
Heather Blewett ◽  
Karmin O ◽  
Yaw L. Siow
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Cells ◽  
Control Group ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Induced Apoptosis ◽  
Hoechst Staining

Lingonberry grown in northern Manitoba, Canada, contains exceptionally high levels of anthocyanins and other polyphenols. Previous studies from our lab have shown that lingonberry anthocyanins can protect H9c2 cells from ischemia–reperfusion injury and anthocyanin-rich diets have been shown to be associated with decreased cardiovascular disease and mortality. Oxidative stress can impair function and trigger apoptosis in cardiomyocytes. This study investigated the protective effects of physiologically relevant doses of lingonberry extracts and pure anthocyanins against hydrogen-peroxide-induced cell death. Apoptosis and necrosis were detected in H9c2 cells after hydrogen peroxide treatment via flow cytometry using FLICA 660 caspase 3/7 combined with YO-PRO-1 and then confirmed with Hoechst staining and fluorescence microscopy. Each of the 3 major anthocyanins found in lingonberry (cyanidin-3-galactoside, cyanidin-3-glucoside, and cyanidin-3-arabinoside) was protective against hydrogen-peroxide-induced apoptosis in H9c2 cells at 10 ng·mL−1 (20 nmol·L−1) and restored the number of viable cells to match the control group. A combination of the 3 anthocyanins was also protective and a lingonberry extract tested at 3 concentrations produced a dose-dependent protective effect. Lingonberry anthocyanins protected cardiac cells from oxidative-stress-induced apoptosis and may have cardioprotective effects as a dietary modification.

scholarly journals FGF-2 Transcriptionally Down-Regulates the Expression of BNIP3L via PI3K/Akt/FoxO3a Signaling and Inhibits Necrosis and Mitochondrial Dysfunction Induced by High Concentrations of Hydrogen Peroxide in H9c2 Cells

2016 ◽  
Vol 40 (6) ◽  
pp. 1678-1691 ◽  
Author(s):  
Qian Chen ◽  
Xiaosong Chen ◽  
Conghui Han ◽  
Ying Wang ◽  
Tao Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Mitochondrial Dysfunction ◽  
Gene Promoter ◽  
Luciferase Assay ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Akt Inhibitor ◽  
H9c2 Cardiomyocytes ◽  
H9c2 Cardiomyoblast Cells

Background/Aims: Cardiovascular disease is a growing major global public health problem. Necrosis is one of the main forms of cardiomyocyte death in heart disease. Oxidative stress is regarded as one of the key regulators of cardiac necrosis, which eventually leads to cardiovascular disease. Many pharmacological and in vitro studies have suggested that FGF-2 can act directly on cardiomyocytes to maintain the integrity and function of the myocardium and prevent damage during oxidative stress. However, the mechanisms by which FGF-2 rescues the myocardium from oxidative stress damage in cardiovascular disease remain unclear. The present study explored the protective effects of FGF-2 in the H2O2-induced necrosis of H9C2 cardiomyocytes as well as the possible signaling pathways involved. Methods: Necrosis of H9c2 cardiomyocytes was induced by H2O2 and assessed using a Cell Counting Kit-8 (CCK8) assay and flow cytometry analysis. The cells were pretreated with the PI3K/Akt inhibitor Wortmannin to investigate the possible involvement of the PI3K/Akt pathway in the protection by FGF-2. The levels of Akt, p-Akt, FoxO3a, p-FoxO3a, and BNIP3L were detected by Western blot. Chromatin immuno-precipitation (ChIP) analysis was used to test whether FoxO3a binds directly to the BNIP3L promoter region. A luciferase assay was used to study the effects of FoxO3a on BNIP3L gene promoter activity. Mitochondrial ΔΨM was quantified using tetramethylrhodamine methyl ester perchlorate (TMRM). The mitochondrial oxygen consumption rate (OCR) was assessed with a Seahorse XF24 Analyzer. Results: Treatment with H2O2 decreased the phosphorylation of Akt and FoxO3a, and it induced the nuclear localization of FoxO3a and the necrosis of H9c2 cells. These effects of H2O2 were abrogated by pretreatment with FGF-2. Furthermore, the protective effects of FGF-2 were abolished by the PI3K/Akt inhibitor Wortmannin. ChIP analyses indicated that FoxO3a binds directly to the BNIP3L promoter region. Using a luciferase assay, we further observed that FoxO3a increased BNIP3L gene promoter activity. As expected, overexpression of BNIP3L in H9C2 cardiomyoblast cells reduced the cardioprotection of FGF-2 in H2O2-induced necrosis and mitochondrial dysfunction. Conclusions: The present data suggest that FGF-2 protects against H2O2-induced necrosis of H9C2 cardiomyocytes via the activation of the PI3K/Akt/FoxO3a pathway. Moreover, the present results demonstrate that FoxO3a is an important transcription factor that acts by binding to the promoter and promoting the transcription of BNIP3L, and it contributes to the necrosis and mitochondrial dysfunction induced by H2O2 in H9c2 cardiomyoblast cells.

SGLT1 knockdown prevents glucose fluctuation-induced apoptosis of cardiomyocytes through attenuating oxidative stress and mitochondrial dysfunction

2020 ◽  
Author(s):  
Qian Chai ◽  
Jiajing Miao ◽  
Meili Liu ◽  
Ziying Zhang ◽  
Ziang Meng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Cardiovascular Complications ◽  
H9c2 Cells ◽  
Glucose Fluctuation ◽  
Sodium Glucose Cotransporter ◽  
Antioxidase Activity ◽  
H9c2 Cardiomyocytes ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Blood glucose fluctuation has been validated to be more detrimental than constant high glucose in the development of cardiovascular complications of diabetes mellitus (DM). Sodium‑glucose cotransporter 2 (SGLT2) inhibitors have been developed as antidiabetic drugs with cardiovascular benefits. However, whether inhibition of SGLT1 protects the diabetic heart remains to be elucidated. The present study investigated the role of SGLT1 in rat H9c2 cardiomyocytes subjected to glucose fluctuation and the underlying mechanisms. The results indicated that SGLT1 knockdown was able to restore cell proliferation and suppress cytotoxicity induced by glucose fluctuation. Glucose fluctuation induced oxidative stress in H9c2 cells, while these changes were reversed effectively by SGLT1 knockdown, as manifested by reduction of intracellular reactive oxygen species and increased antioxidase activity. Further study demonstrated that SGLT1 knockdown attenuated mitochondrial dysfunction in H9c2 cells exposed to glucose fluctuation, including restoration of mitochondrial membrane potential and promotion of mitochondrial fusion. In addition, SGLT1 knockdown downregulated Bax expression, upregulated Bcl-2 expression, and reduced caspase-3 activation in glucose fluctuation-induced H9c2 cells. Taken together, our study reveals that SGLT1 knockdown ameliorates glucose fluctuation-induced cardiomyocyte apoptosis, which might be ascribed to regulation of oxidative stress and mitochondrial dysfunction.

Cardioprotective effect of KR-33889, a novel PARP inhibitor, against oxidative stress-induced apoptosis in H9c2 cells and isolated rat hearts

2017 ◽  
Vol 40 (5) ◽  
pp. 640-654 ◽  
Author(s):  
Eun-Seok Park ◽  
Do-Hyun Kang ◽  
Jun Chul Kang ◽  
Yong Chang Jang ◽  
Min-Ju Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parp Inhibitor ◽  
Cardioprotective Effect ◽  
H9c2 Cells ◽  
Rat Hearts ◽  
Induced Apoptosis ◽  
Isolated Rat

scholarly journals Effects of Four Compounds from Gentianella acuta (Michx.) Hulten on Hydrogen Peroxide-Induced Injury in H9c2 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Kai Ren ◽  
He Su ◽  
Li-juan Lv ◽  
Le-tai Yi ◽  
Xue Gong ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Protein Expression ◽  
Treated Group ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Mtt Method ◽  
Bioassay Guided Fractionation ◽  
Induced Apoptosis

In previous studies, Gentianella acuta (Michx.) Hulten was reported to contain xanthones, iridoids, terpenoids, and sterols and is mainly used to cure hepatitis, jaundice, fever, headache, and angina pectoris. In this study, we used bioassay guided fractionation to identify compounds from G. acuta and investigated their activity against hydrogen peroxide (H2O2)-induced apoptosis of H9c2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic (GCLC) expression were assessed using quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was evaluated using western blot. The results showed that all four compounds had protective effects on H9c2 cells. The transcription levels of HO-1 and GCLC significantly increased in H9c2 cells pretreated with norswertianolin (1), swetrianolin (2), demethylbellidifolin (3), and bellidifolin (4). However, compared to the model group, the transcription levels of Nrf2 were not enhanced by pretreatment with compounds 1, 2, and 4. The protein expression levels of HO-1 and GCLC in H9c2 cells were greater than that in the H2O2-treated group, and the expression of Nrf2 was not significantly changed except by swetrianolin treatment; inhibitors can reverse the protective effect by ZnPP (15 μM), BSO (10 μM), and brusatol (10 μM). The results indicated that the four compounds isolated from G. acuta inhibited the oxidative injury induced by H2O2 by activating the Nrf2/ARE pathway in H9c2 cells and provide evidence that G. acuta may be a potential therapeutic agent for the treatment of cardiovascular diseases.

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