N-Acetyl-Serotonin Protects HepG2 Cells from Oxidative Stress Injury Induced by Hydrogen Peroxide

Oxidative stress plays an important role in the pathogenesis of liver diseases. N-Acetyl-serotonin (NAS) has been reported to protect against oxidative damage, though the mechanisms by which NAS protects hepatocytes from oxidative stress remain unknown. To determine whether pretreatment with NAS could reduce hydrogen peroxide- (H2O2-) induced oxidative stress in HepG2 cells by inhibiting the mitochondrial apoptosis pathway, we investigated the H2O2-induced oxidative damage to HepG2 cells with or without NAS using MTT, Hoechst 33342, rhodamine 123, Terminal dUTP Nick End Labeling Assay (TUNEL), dihydrodichlorofluorescein (H2DCF), Annexin V and propidium iodide (PI) double staining, immunocytochemistry, and western blot. H2O2produced dramatic injuries in HepG2 cells, represented by classical morphological changes of apoptosis, increased levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), decreased activity of superoxide dismutase (SOD), and increased activities of caspase-9 and caspase-3, release of cytochrome c (Cyt-C) and apoptosis-inducing factor (AIF) from mitochondria, and loss of membrane potential (ΔΨm). NAS significantly inhibited H2O2-induced changes, indicating that it protected against H2O2-induced oxidative damage by reducing MDA levels and increasing SOD activity and that it protected the HepG2 cells from apoptosis through regulating the mitochondrial apoptosis pathway, involving inhibition of mitochondrial hyperpolarization, release of mitochondrial apoptogenic factors, and caspase activity.

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S-Allyl Cysteine Alleviates Hydrogen Peroxide Induced Oxidative Injury and Apoptosis through Upregulation of Akt/Nrf-2/HO-1 Signaling Pathway in HepG2 Cells

BioMed Research International ◽

10.1155/2018/3169431 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14 ◽

Cited By ~ 6

Author(s):

Chitra Basu ◽

Runa Sur

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Oxidative Damage ◽

Hepg2 Cells ◽

Liver Diseases ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Dependent Manner ◽

Cell Viability Assay

Hydrogen peroxide (H2O2) mediated oxidative stress leading to hepatocyte apoptosis plays a pivotal role in the pathophysiology of several chronic liver diseases. This study demonstrates that S-allyl cysteine (SAC) renders cytoprotective effects on H2O2 induced oxidative damage and apoptosis in HepG2 cells. Cell viability assay showed that SAC protected HepG2 cells from H2O2 induced cytotoxicity. Further, SAC treatment dose dependently inhibited H2O2 induced apoptosis via decreasing the Bax/Bcl-2 ratio, restoring mitochondrial membrane potential (∆Ψm), inhibiting mitochondrial cytochrome c release, and inhibiting proteolytic cleavage of caspase-3. SAC protected cells from H2O2 induced oxidative damage by inhibiting reactive oxygen species accumulation and lipid peroxidation. The mechanism underlying the antiapoptotic and antioxidative role of SAC is the induction of the heme oxygenase-1 (HO-1) gene in an NF-E2-related factor-2 (Nrf-2) and Akt dependent manner. Specifically SAC was found to induce the phosphorylation of Akt and enhance the nuclear localization of Nrf-2 in cells. Our results were further confirmed by specific HO-1 gene knockdown studies which clearly demonstrated that HO-1 induction indeed played a key role in SAC mediated inhibition of apoptosis and ROS production in HepG2 cells, thus suggesting a hepatoprotective role of SAC in combating oxidative stress mediated liver diseases.

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Camalexin Induces Apoptosis via the ROS-ER Stress-Mitochondrial Apoptosis Pathway in AML Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/7426950 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Yang Yang ◽

Gang Wang ◽

Wenjun Wu ◽

Shunnan Yao ◽

Xiaoyan Han ◽

...

Keyword(s):

Er Stress ◽

Plant Pathogens ◽

Leukemic Cells ◽

Dependent Manner ◽

Mitochondrial Apoptosis ◽

Antitumor Effects ◽

Sod Activity ◽

Apoptosis Pathway ◽

Mitochondrial Apoptosis Pathway

Camalexin is a phytoalexin that accumulates in various cruciferous plants upon exposure to environmental stress and plant pathogens. It was shown that camalexin has potent antitumor properties, but its underlying mechanisms are still elusive. In the present study, we evaluated the effects of camalexin on human leukemic cells and normal polymorph nuclear cells. CCK-8 assay was used to determine cell viability after camalexin treatment. Apoptosis, intracellular reactive oxygen species (ROS) levels, and loss of mitochondrial membrane potential (MMP) were measured by flow cytometry. The activity of SOD, catalase, and ratio of GSH/GSSG were assayed. ER stress and apoptotic signaling pathway was examined by Western blot. Xenograft mice were used to verify the effect of camalexin in vivo. Our results indicated that camalexin inhibited viability of leukemic but not normal polymorph nuclear cells. Furthermore, camalexin induces apoptosis via the mitochondrial pathway in a caspase-dependent manner. We also observed ER stress is located upstream of apoptosis induced by camalexin. Besides, ROS levels, SOD activity, CAT activity, and GSSG levels were significantly enhanced while the GSH level was decreased after treatment of camalexin. In addition, the generation of ROS is critical for the ER stress and apoptosis induced by camalexin. Finally, administration of camalexin suppresses xenograft tumor graft growth without obvious toxicity. Taken together, this study indicates that camalexin exerts antitumor effects against leukemia cells via the ROS-ER stress-mitochondrial apoptosis pathway.

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Corrigendum to “Aspirin eugenol ester ameliorates paraquat-induced oxidative damage through ROS/p38-MAPK-mediated mitochondrial apoptosis pathway” [Toxicology 453 (2021) 152721]

Toxicology ◽

10.1016/j.tox.2021.152763 ◽

2021 ◽

Vol 454 ◽

pp. 152763

Author(s):

Zhen-Dong Zhang ◽

Ya-Jun Yang ◽

Xi-Wang Liu ◽

Zhe Qin ◽

Shi-Hong Li ◽

...

Keyword(s):

Oxidative Damage ◽

P38 Mapk ◽

Mitochondrial Apoptosis ◽

Apoptosis Pathway ◽

Mitochondrial Apoptosis Pathway ◽

Aspirin Eugenol Ester

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Myricitrin Protects against Doxorubicin-Induced Cardiotoxicity by Counteracting Oxidative Stress and Inhibiting Mitochondrial Apoptosis via ERK/P53 Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/6093783 ◽

2016 ◽

Vol 2016 ◽

pp. 1-16 ◽

Cited By ~ 15

Author(s):

Jing Sun ◽

Guibo Sun ◽

Xiaolan Cui ◽

Xiangbao Meng ◽

Meng Qin ◽

...

Keyword(s):

Oxidative Stress ◽

Myocardial Damage ◽

Mitochondrial Apoptosis ◽

Mechanism Study ◽

Apoptosis Pathway ◽

Mitochondrial Apoptosis Pathway ◽

Myocardial Apoptosis ◽

Underlying Mechanisms

Doxorubicin (Dox) is one of the most effective and widely used anthracycline antineoplastic antibiotics. Unfortunately, the use of Dox is limited by its cumulative and dose-dependent cardiac toxicity. Myricitrin, a natural flavonoid which is isolated from the ground bark ofMyrica rubra, has recently been found to have a strong antioxidative effect. This study aimed to evaluate the possible protective effect of myricitrin against Dox-induced cardiotoxicity and the underlying mechanisms. An in vivo investigation in SD rats demonstrated that myricitrin significantly reduced the Dox-induced myocardial damage, as indicated by the decreases in the cardiac index, amelioration of heart pathological injuries, and decreases in the serum cardiac enzyme levels. In addition, in vitro studies showed that myricitrin effectively reduced the Dox-induced cell toxicity. Further study showed that myricitrin exerted its function by counteracting oxidative stress and increasing the activities of antioxidant enzymes. Moreover, myricitrin suppressed the myocardial apoptosis induced by Dox, as indicated by decreases in the activation of caspase-3 and the numbers of TUNEL-positive cells, maintenance of the mitochondrial membrane potential, and increase in the Bcl-2/Bax ratio. Further mechanism study revealed that myricitrin-induced suppression of myocardial apoptosis relied on the ERK/p53-mediated mitochondrial apoptosis pathway.

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Ebselen protects mitochondrial function and oxidative stress while inhibiting the mitochondrial apoptosis pathway after acute spinal cord injury

Neuroscience Letters ◽

10.1016/j.neulet.2018.05.007 ◽

2018 ◽

Vol 678 ◽

pp. 110-117 ◽

Cited By ~ 6

Author(s):

Zhi-Qiang Jia ◽

San-Qiang Li ◽

Wei-Qiang Qiao ◽

Wen-Zhong Xu ◽

Jian-Wu Xing ◽

...

Keyword(s):

Oxidative Stress ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Mitochondrial Function ◽

Acute Spinal Cord Injury ◽

Mitochondrial Apoptosis ◽

Apoptosis Pathway ◽

Mitochondrial Apoptosis Pathway ◽

Cord Injury ◽

And Oxidative Stress

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Matrine Exerts Hepatotoxic Effects via the ROS-Dependent Mitochondrial Apoptosis Pathway and Inhibition of Nrf2-Mediated Antioxidant Response

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/1045345 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 8

Author(s):

Longtai You ◽

Chunjing Yang ◽

Yuanyuan Du ◽

Yi Liu ◽

Gongsen Chen ◽

...

Keyword(s):

Antioxidant Response ◽

S Phase ◽

Activity Level ◽

Heme Oxygenase 1 ◽

Mitochondrial Apoptosis ◽

Sod Activity ◽

Apoptosis Pathway ◽

Mitochondrial Apoptosis Pathway ◽

Wide Range ◽

Hepatotoxic Effect

Matrine, an alkaloid isolated from Sophora flavescens, possesses a wide range of pharmacological properties. However, the use of matrine in clinical practice is limited due to its toxic effects. The present study investigated the roles of mitochondria and reactive oxygen species (ROS) in matrine-induced liver injury. Our results showed that treatment of HL-7702 cells with matrine led to significant and concentration- and time-dependent reductions in their viability, as well as significant and concentration-dependent increases in the number of apoptotic cells and supernatant lactate dehydrogenase (LDH) activity. The treatment led to significant increases in the population of cells in S phase and significant reduction of cell proportion in G0/G1 and G2/M phases. It also significantly and concentration-dependently increased the levels of ROS and malondialdehyde (MDA) but significantly and concentration-dependently reduced superoxide dismutase (SOD) activity, level of reduced glutathione (GSH), and mitochondrial membrane potential (MMP). Matrine treatment significantly and concentration-dependently upregulated the expressions of Bax, p53, p-p53, p21, cyclin E, Fas, cleaved caspase-3, caspase-8, and caspase-9 proteins and downregulated the expressions of Bcl-2, cyclin-dependent kinase 2 (CDK2), and cyclin A. It also significantly promoted the cleavage of poly(ADP-ribose)polymerase (PARP), upregulated Kelch-like ECH-associated protein 1 (Keap1) expression, and downregulated the expressions of cellular total and nuclear Nrf2. Matrine significantly inhibited the expressions of downstream oxidoreductases (Heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductases 1 (NQO-1)) and enhanced the formation of Keap1/Nrf2 protein complex. These results show that the hepatotoxic effect of matrine is exerted via inhibition of Nrf2 pathway, activation of ROS-mediated mitochondrial apoptosis pathway, and cell cycle arrest at S phase. Pretreatment with N-acetyl cysteine (NAC) partially reversed matrine-induced hepatotoxicity.

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Selenium deficiency induces duodenal villi cell apoptosis via an oxidative stress-induced mitochondrial apoptosis pathway and an inflammatory signaling-induced death receptor pathway

Metallomics ◽

10.1039/c8mt00142a ◽

2018 ◽

Vol 10 (10) ◽

pp. 1390-1400 ◽

Cited By ~ 15

Author(s):

Jianfa Wang ◽

Zhe Liu ◽

Xianjing He ◽

Shuai Lian ◽

Jianbin Liang ◽

...

Keyword(s):

Oxidative Stress ◽

Trace Element ◽

Cell Apoptosis ◽

Death Receptor ◽

Selenium Deficiency ◽

Mitochondrial Apoptosis ◽

Inflammatory Signaling ◽

Apoptosis Pathway ◽

Death Receptor Pathway ◽

Mitochondrial Apoptosis Pathway

Selenium is an important nutritional trace element possessing antioxidant and anti-apoptotic properties in intestinal.

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Protective Effect of N-Acetylcysteine against Oxidative Stress Induced by Zearalenone via Mitochondrial Apoptosis Pathway in SIEC02 Cells

Toxins ◽

10.3390/toxins10100407 ◽

2018 ◽

Vol 10 (10) ◽

pp. 407 ◽

Cited By ~ 7

Author(s):

Jingjing Wang ◽

Mengmeng Li ◽

Wei Zhang ◽

Aixin Gu ◽

Jiawen Dong ◽

...

Keyword(s):

Oxidative Stress ◽

Messenger Rna ◽

Caspase 3 ◽

Intestinal Epithelial ◽

Mitochondrial Apoptosis ◽

Caspase 9 ◽

Treatment Results ◽

Apoptosis Pathway ◽

Mitochondrial Apoptosis Pathway ◽

Small Intestinal

Zearalenone (ZEN), a nonsteroidal estrogen mycotoxin, is widely found in feed and foodstuffs. Intestinal cells may become the primary target of toxin attack after ingesting food containing ZEN. Porcine small intestinal epithelial (SIEC02) cells were selected to assess the effect of ZEN exposure on the intestine. Cells were exposed to ZEN (20 µg/mL) or pretreated with (81, 162, and 324 µg/mL) N-acetylcysteine (NAC) prior to ZEN treatment. Results indicated that the activities of glutathione peroxidase (Gpx) and glutathione reductase (GR) were reduced by ZEN, which induced reactive oxygen species (ROS) and malondialdehyde (MDA) production. Moreover, these activities increased apoptosis and mitochondrial membrane potential (ΔΨm), and regulated the messenger RNA (mRNA) expression of Bax, Bcl-2, caspase-3, caspase-9, and cytochrome c (cyto c). Additionally, NAC pretreatment reduced the oxidative damage and inhibited the apoptosis induced by ZEN. It can be concluded that ZEN-induced oxidative stress and damage may further induce mitochondrial apoptosis, and pretreatment of NAC can degrade this damage to some extent.

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