Inhibition of NADPH oxidase by apocynin promotes myocardial antioxidant response and prevents isoproterenol-induced myocardial oxidative stress in rats

Tanriverdi, Lokman Hekim; Parlakpınar, Hakan; Özhan, Onural; Ermiş, Necip; Polat, Alaadin; Vardı, Nigar; Tanbek, Kevser; Yıldız, Azibe; Acet, Ahmet

doi:10.1080/10715762.2017.1375486

Cited by 27 publications

(18 citation statements)

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“…The damaged enzymes, which have the role of electron transferring in the mitochondria, causing the electron transfer to oxygen, in turn resulting in the generation of superoxide, that is, the initial ROS molecule. Also, deterioration of the balance between formation rate of oxidant molecules and antioxidant defenses leads to oxidative stress, which is related to myocardial hyperfunction …”

Section: Discussionmentioning

confidence: 99%

Protective and therapeutic effects of dexpanthenol on isoproterenol‐induced cardiac damage in rats

Kalkan

Parlakpınar

Disli

et al. 2018

J of Cellular Biochemistry

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The purpose of the study was to explore the protective and therapeutic effects of dexpanthenol (DEX) on isoproterenol (ISO)-induced cardiac damage. Forty rats were distributed into four groups: group I (Control); group II (ISO); ISO (150 mg/kg/day) was given to rats once a day for 2 consecutive days with an interval of 24 h; group III (DEX+ISO): DEX (250 mg/kg) was applied 30 min before the first ISO administration and continued in the next two days after second ISO administration; group IV (ISO+DEX): After the ISO treatment at 1st and 2nd days, DEX was given at 3rd and 4th days. Rats were monitored for mean arterial blood pressure (BP), heart rate, oxygen saturation (%SO ), and electrocardiography (ECG). Heart tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), reduced glutathione (GSH), total oxidant status (TOS); total antioxidant capacity (TAC), oxidative stress index (OSI), and caspase-3 were determined. BP and SO values indicated a significant decrease in the ISO group. Also, T wave negativity was observed in 6 of 10 rats, SOD, CAT, and GPX levels were significantly lower in ISO group than control group. ISO administration increased TOS and OSI levels, whereas DEX treatment significantly reduced these parameters. Also, ISO-induced morphological alterations such as disorganization of cardiomyocytes, loss of myofibrils and cytoplasmic vacuolization whereas these histological damages were significantly decreased in ISO+DEX and DEX+ISO groups when compared to the ISO group. This study implies the cardioprotective effects of DEX on ISO-induced cardiotoxicity.

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Section: Discussionmentioning

confidence: 99%

Protective and therapeutic effects of dexpanthenol on isoproterenol‐induced cardiac damage in rats

Kalkan

Parlakpınar

Disli

et al. 2018

J of Cellular Biochemistry

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“…Of these, Nox2 and Nox4 are highly expressed in the cardiomyocytes mediating both adaptive and maladaptive changes in the heart [8]. Nox activity is reported to be elevated in cardiac dysfunction under different disease states including sepsis, ischemic cardiomyopathy, and heart failure [9, 10]. Increasing evidence has shown that Nox is activated by various stimuli like proinflammatory cytokine TNF- α , endothelin-1 (ET-1), and endotoxin [11–13].…”

Section: Introductionmentioning

confidence: 99%

NADPH Oxidase Hyperactivity Contributes to Cardiac Dysfunction and Apoptosis in Rats with Severe Experimental Pancreatitis through ROS-Mediated MAPK Signaling Pathway

Wen

Liu

Lin

et al. 2019

Oxidative Medicine and Cellular Longevity

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NADPH oxidase (Nox) is considered a major source of reactive oxygen species (ROS) in the heart in normal and pathological conditions. However, the role of Nox in severe acute pancreatitis- (SAP-) associated cardiac injury remains unclear. Therefore, we aim to investigate the contribution of Nox to SAP-associated cardiac injury and to explore the underlying molecular mechanisms. Apocynin, a Nox inhibitor, was given at 20 mg/kg for 30 min before SAP induction by a retrograde pancreatic duct injection of 5% sodium taurocholate. Histopathological staining, Nox activity and protein expression, oxidative stress markers, apoptosis and associated proteins, cardiac-related enzyme indexes, and cardiac function were assessed in the myocardium in SAP rats. The redox-sensitive MAPK signaling molecules were also examined by western blotting. SAP rats exhibited significant cardiac impairment along with increased Nox activity and protein expression, ROS production, cell apoptosis, and proapoptotic Bax and cleaved caspase-3 protein levels. Notably, Nox inhibition with apocynin prevented SAP-associated cardiac injury evidenced by a decreased histopathologic score, cardiac-related enzymes, and cardiac function through the reduction of ROS production and cell apoptosis. This protective role was further confirmed by a simulation experiment in vitro. Moreover, we found that SAP-induced activation in MAPK signaling molecules in cardiomyocytes was significantly attenuated by Nox inhibition. Our data provide the first evidence that Nox hyperactivation acts as the main source of ROS production in the myocardium, increases oxidative stress, and promotes cell apoptosis via activating the MAPK pathway, which ultimately results in cardiac injury in SAP.

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“…NAC, a N -acetyl derivative of L-cysteine and a precursor of the reduced glutathione (GSH), acts as an antioxidant [ 52 ]. Apocynin is a NADPH oxidase (NOX) inhibitor and acts by scavenging the superoxide anion (O 2 −• ), which is generated during the reduction of O 2 by NOX in order to abate the oxidative stress and inflammation [ 53 ]. Curcumin, also known as diferuloylmethane (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), is a natural polyphenol found in the rhizome of Curcuma longa (turmeric) and is known to have antioxidant, antiinflammatory, antimicrobial, and antimutagenic or anticancer properties [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

MIP-1α Expression Induced by Co-Stimulation of Human Monocytic Cells with Palmitate and TNF-α Involves the TLR4-IRF3 Pathway and Is Amplified by Oxidative Stress

Sindhu

Akhter

Wilson

et al. 2020

Cells

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Metabolic inflammation is associated with increased expression of saturated free fatty acids, proinflammatory cytokines, chemokines, and adipose oxidative stress. Macrophage inflammatory protein (MIP)-1α recruits the inflammatory cells such as monocytes, macrophages, and neutrophils in the adipose tissue; however, the mechanisms promoting the MIP-1α expression remain unclear. We hypothesized that MIP-1α co-induced by palmitate and tumor necrosis factor (TNF)-α in monocytic cells/macrophages could be further enhanced in the presence of reactive oxygen species (ROS)-mediated oxidative stress. To investigate this, THP-1 monocytic cells and primary human macrophages were co-stimulated with palmitate and TNF-α and mRNA and protein levels of MIP-1α were measured by using quantitative reverse transcription, polymerase chain reaction (qRT-PCR) and commercial enzyme-linked immunosorbent assays (ELISA), respectively. The cognate receptor of palmitate, toll-like receptor (TLR)-4, was blunted by genetic ablation, neutralization, and chemical inhibition. The involvement of TLR4-downstream pathways, interferon regulatory factor (IRF)-3 or myeloid differentiation (MyD)-88 factor, was determined using IRF3-siRNA or MyD88-deficient cells. Oxidative stress was induced in cells by hydrogen peroxide (H2O2) treatment and ROS induction was measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. The data show that MIP-1α gene/protein expression was upregulated in cells co-stimulated with palmitate/TNF-α compared to those stimulated with either palmitate or TNF-α (P < 0.05). Further, TLR4-IRF3 pathway was implicated in the cooperative induction of MIP-1α in THP-1 cells, and this cooperativity between palmitate and TNF-α was clathrin-dependent and also required signaling through c-Jun and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Notably, ROS itself induced MIP-1α and could further promote MIP-1α secretion together with palmitate and TNF-α. In conclusion, palmitate and TNF-α co-induce MIP-1α in human monocytic cells via the TLR4-IRF3 pathway and signaling involving c-Jun/NF-κB. Importantly, oxidative stress leads to ROS-driven MIP-1α amplification, which may have significance for metabolic inflammation.

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Inhibition of NADPH oxidase by apocynin promotes myocardial antioxidant response and prevents isoproterenol-induced myocardial oxidative stress in rats

Cited by 27 publications

References 77 publications

Protective and therapeutic effects of dexpanthenol on isoproterenol‐induced cardiac damage in rats

Protective and therapeutic effects of dexpanthenol on isoproterenol‐induced cardiac damage in rats

NADPH Oxidase Hyperactivity Contributes to Cardiac Dysfunction and Apoptosis in Rats with Severe Experimental Pancreatitis through ROS-Mediated MAPK Signaling Pathway

MIP-1α Expression Induced by Co-Stimulation of Human Monocytic Cells with Palmitate and TNF-α Involves the TLR4-IRF3 Pathway and Is Amplified by Oxidative Stress

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