scholarly journals Nano-Curcumin Prevents Cardiac Injury, Oxidative Stress and Inflammation, and Modulates TLR4/NF-κB and MAPK Signaling in Copper Sulfate-Intoxicated Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1414
Author(s):  
Wedad S. Sarawi ◽  
Ahlam M. Alhusaini ◽  
Laila M. Fadda ◽  
Hatun A. Alomar ◽  
Awatif B. Albaker ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Copper Sulfate ◽  
Troponin I ◽  
Tissue Injury ◽  
Cardiac Injury ◽  
Elevated Serum ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Native Form ◽  
Tnf Α

Copper (Cu) is essential for a plethora of biological processes; however, its high redox reactivity renders it potentially toxic. This study investigated the protective effect of curcumin (CUR) and nano-CUR (N-CUR) against Cu cardiotoxicity, emphasizing the role of oxidative stress, TLR4/NF-κB and mitogen-activated protein kinase (MAPK) signaling and cell death in rats. Rats received 100 mg/kg copper sulfate (CuSO4), a pesticide used for repelling pests, and were concurrently treated with CUR or N-CUR for 7 days. Cu caused cardiac injury manifested by elevated serum cardiac troponin I (cTnI), creatine kinase (CK)-MB, and lactate dehydrogenase (LDH), as well as histopathological alterations. Cardiac malondialdehyde (MDA), NF-κB p65, TNF-α, and IL-6 were increased, and reduced glutathione (GSH), superoxide dismutase (SOD) and catalase were decreased in Cu-treated rats. CUR and N-CUR prevented cardiac tissue injury, decreased serum cTnI, CK-MB, and LDH, and cardiac MDA, NF-κB p65, TNF-α, and IL-6, and enhanced cellular antioxidants. CUR and N-CUR downregulated TLR4 and AP-1, and decreased the phosphorylation levels of p38 MAPK, JNK, and ERK1/2. In addition, CUR and N-CUR increased cardiac Bcl-2 and BAG-1, decreased Bax and caspase-3, and prevented DNA fragmentation. In conclusion, N-CUR prevents Cu cardiotoxicity by attenuating oxidative injury, inflammatory response, and apoptosis, and modulating TLR4/NF-κB and MAPK signaling. The cardioprotective effect of N-CUR was more potent than the native form.

scholarly journals Curcumin Ameliorates Lead-Induced Hepatotoxicity by Suppressing Oxidative Stress and Inflammation, and Modulating Akt/GSK-3β Signaling Pathway

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 703 ◽  
Author(s):  
Ahlam Alhusaini ◽  
Laila Fadda ◽  
Iman H. Hasan ◽  
Enas Zakaria ◽  
Abeer M. Alenazi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Tissue Injury ◽  
Elevated Serum ◽  
Antioxidant Defenses ◽  
Exact Role ◽  
Toxic Heavy Metal ◽  
Tnf Α ◽  
Gsk 3Β

Lead (Pb) is a toxic heavy metal pollutant with adverse effects on the liver and other body organs. Curcumin (CUR) is the principal curcuminoid of turmeric and possesses strong antioxidant and anti-inflammatory activities. This study explored the protective effect of CUR on Pb hepatotoxicity with an emphasis on oxidative stress, inflammation and Akt/GSK-3β signaling. Rats received lead acetate and CUR and/or ascorbic acid (AA) for seven days and samples were collected for analyses. Pb(II) induced liver injury manifested by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as histopathological alterations, including massive hepatocyte degeneration and increased collagen deposition. Lipid peroxidation, nitric oxide, TNF-α and DNA fragmentation were increased, whereas antioxidant defenses were diminished in the liver of Pb(II)-intoxicated rats. Pb(II) increased hepatic NF-κB and JNK phosphorylation and caspase-3 cleavage, whereas Akt and GSK-3β phosphorylation was decreased. CUR and/or AA ameliorated liver function, prevented tissue injury, and suppressed oxidative stress, DNA damage, NF-κB, JNK and caspase-3. In addition, CUR and/or AA activated Akt and inhibited GSK-3β in Pb(II)-induced rats. In conclusion, CUR prevents Pb(II) hepatotoxicity via attenuation of oxidative injury and inflammation, activation of Akt and inhibition of GSK-3β. However, further studies scrutinizing the exact role of Akt/GSK-3β signaling are recommended.

scholarly journals (–)-Loliolide Isolated from Sargassum horneri Suppressed Oxidative Stress and Inflammation by Activating Nrf2/HO-1 Signaling in IFN-γ/TNF-α-Stimulated HaCaT Keratinocytes

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 856
Author(s):  
Eui-Jeong Han ◽  
Ilekuttige Priyan Shanura Fernando ◽  
Hyun-Soo Kim ◽  
Dae-Sung Lee ◽  
Areum Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nuclear Factor Κb ◽  
Sargassum Horneri ◽  
Mitogen Activated Protein Kinase ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Hacat Keratinocytes ◽  
Tnf Α ◽  
Ifn Γ

The present study evaluated the effects of (–)-loliolide isolated from Sargassum horneri (S. horneri) against oxidative stress and inflammation, and its biological mechanism in interferon (IFN)-γ/tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocytes. The results showed that (–)-loliolide improved the cell viability by reducing the production of intracellular reactive oxygen species (ROS) in IFN-γ/TNF-α-stimulated HaCaT keratinocytes. In addition, (–)-loliolide effectively decreased the expression of inflammatory cytokines (interleukin (IL)-4 IL-6, IL-13, IFN-γ and TNF-α) and chemokines (CCL11 (Eotaxin), macrophage-derived chemokine (MDC), regulated on activation, normal T cell expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC)), by downregulating the expression of epidermal-derived initial cytokines (IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)). Furthermore, (–)-loliolide suppressed the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling, whereas it activated nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Interestingly, the cytoprotective effects of (–)-loliolide against IFN-γ/TNF-α stimulation were significantly blocked upon inhibition of HO-1. Taken together, these results suggest that (–)-loliolide effectively suppressed the oxidative stress and inflammation by activating the Nrf2/HO-1 signaling in IFN-γ/TNF-α-stimulated HaCaT keratinocytes.

scholarly journals Salidroside pretreatment protects against myocardial injury induced by heat stroke in mice

2019 ◽  
Vol 47 (10) ◽  
pp. 5229-5238
Author(s):  
Guo-dong Chen ◽  
Heng Fan ◽  
Jian-Hua Zhu
Keyword(s):  
Oxidative Stress ◽  
Myocardial Injury ◽  
Troponin I ◽  
Heat Stroke ◽  
Cardiac Injury ◽  
Myocardial Damage ◽  
Thiobarbituric Acid ◽  
Protective Effects ◽  
Creatine Kinase Mb ◽  
Factor Α

Objective To explore the protective effects and mechanisms of salidroside on myocardial injury induced by heat stroke (HS) in mice. Methods We pretreated mice with salidroside for 1 week and then established an HS model by exposure to 41.2°C for 1 hour. We then examined the effects of salidroside on survival. We also assessed the severity of cardiac injury by pathology, and analyzed changes in levels of myocardial injury markers, inflammatory cytokines, and oxidative stress. Results Salidroside pretreatment significantly reduced HS-induced mortality and improved thermoregulatory function. Salidroside also provided significant protection against HS-induced myocardial damage, and decreased the expression levels of cardiac troponin I, creatine kinase-MB, and lactate dehydrogenase. Moreover, salidroside attenuated HS-induced changes in the inflammation markers tumor necrosis factor-α, interleukin (IL)-6, and IL-10, and down-regulated the oxidative stress response indicated by thiobarbituric acid reactant substances, malondialdehyde, reduced glutathione, and superoxide dismutase. Conclusions Salidroside pretreatment protected against HS-induced myocardial damage, potentially via a mechanism involving anti-inflammatory and anti-oxidative effects.

scholarly journals Honokiol ameliorates radiation-induced brain injury via the activation of SIRT3

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096399
Author(s):  
Guixiang Liao ◽  
Zhihong Zhao ◽  
Hongli Yang ◽  
Xiaming Li
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Interleukin 1 ◽  
Dependent Manner ◽  
Ht22 Cells ◽  
Tnf Α ◽  
Radiation Induced ◽  
Cox 2

Objective Sirtuin 3 (SIRT3) plays a vital role in regulating oxidative stress in tissue injury. The aim of this study was to evaluate the radioprotective effects of honokiol (HKL) in a zebrafish model of radiation-induced brain injury and in HT22 cells. Methods The levels of reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were evaluated in the zebrafish brain and HT22 cells. The expression levels of SIRT3 and cyclooxygenase-2 (COX-2) were measured using western blot assays and real-time polymerase chain reaction (RT-PCR). Results HKL treatment attenuated the levels of ROS, TNF-α, and IL-1β in both the in vivo and in vitro models of irradiation injury. Furthermore, HKL treatment increased the expression of SIRT3 and decreased the expression of COX-2. The radioprotective effects of HKL were achieved via SIRT3 activation. Conclusions HKL attenuated oxidative stress and pro-inflammatory responses in a SIRT3-dependent manner in radiation-induced brain injury.

scholarly journals MiR-4674 regulates angiogenesis in tissue injury by targeting p38K signaling in endothelial cells

2020 ◽  
Vol 318 (3) ◽  
pp. C524-C535 ◽  
Author(s):  
Basak Icli ◽  
Hao Li ◽  
Daniel Pérez-Cremades ◽  
Winona Wu ◽  
Denizhan Ozdemir ◽  
...  
Keyword(s):  
Tissue Repair ◽  
Tissue Injury ◽  
Interleukin 1 ◽  
Mapk Signaling ◽  
Tube Formation ◽  
Mitogen Activated Protein Kinase ◽  
Small Noncoding Rnas ◽  
Disease States ◽  
Pathological Disease ◽  
Impaired Angiogenesis

Neoangiogenesis is critical for tissue repair in response to injury such as myocardial ischemia or dermal wound healing. MicroRNAs are small noncoding RNAs and important regulators of angiogenesis under physiological and pathological disease states. Therefore, identification of microRNAs that may restore impaired angiogenesis in response to tissue injury may provide new targets for therapy. Using a microRNA microarray profiling approach, we identified a human-specific microRNA, miR-4674, that was significantly decreased in patients after myocardial tissue injury and had an endothelial cell (EC)-enriched expression pattern. Functionally, overexpression of miR-4674 markedly attenuated EC proliferation, migration, network tube formation, and spheroid sprouting, whereas blockade of miR-4674 had the opposite effects. Transcriptomic profiling, gene set enrichment analyses, bioinformatics, 3′-untranslated region (3’-UTR) reporter and microribonucleoprotein immunoprecipitation (miRNP-IP) assays, and small interfering RNA dependency studies revealed that miR-4674 regulates VEGF stimulated-p38 mitogen-activated protein kinase (MAPK) signaling and targets interleukin 1 receptor-associated kinase 1 (Irak1) and BICD cargo adaptor 2 (Bicd2) in ECs. Furthermore, Irak1 and Bicd2 were necessary for miR-4674-driven EC proliferation and migration. Finally, neutralization of miR-4674 increased angiogenesis, Irak1 and Bicd2 expression, and p38 phosphorylation in human skin organoids as a model of tissue injury. Collectively, targeting miR-4674 may provide a novel therapeutic target for tissue repair in pathological disease states associated with impaired angiogenesis.

scholarly journals Epigallocatechin Gallate Modulates Muscle Homeostasis in Type 2 Diabetes and Obesity by Targeting Energetic and Redox Pathways: A Narrative Review

2019 ◽  
Vol 20 (3) ◽  
pp. 532 ◽  
Author(s):  
Ester Casanova ◽  
Josepa Salvadó ◽  
Anna Crescenti ◽  
Albert Gibert-Ramos
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Epigallocatechin Gallate ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Insulin Resistant ◽  
Systemic Signaling

Obesity is associated with the hypertrophy and hyperplasia of adipose tissue, affecting the healthy secretion profile of pro- and anti-inflammatory adipokines. Increased influx of fatty acids and inflammatory adipokines from adipose tissue can induce muscle oxidative stress and inflammation and negatively regulate myocyte metabolism. Muscle has emerged as an important mediator of homeostatic control through the consumption of energy substrates, as well as governing systemic signaling networks. In muscle, obesity is related to decreased glucose uptake, deregulation of lipid metabolism, and mitochondrial dysfunction. This review focuses on the effect of epigallocatechin-gallate (EGCG) on oxidative stress and inflammation, linked to the metabolic dysfunction of skeletal muscle in obesity and their underlying mechanisms. EGCG works by increasing the expression of antioxidant enzymes, by reversing the increase of reactive oxygen species (ROS) production in skeletal muscle and regulating mitochondria-involved autophagy. Moreover, EGCG increases muscle lipid oxidation and stimulates glucose uptake in insulin-resistant skeletal muscle. EGCG acts by modulating cell signaling including the NF-κB, AMP-activated protein kinase (AMPK), and mitogen-activated protein kinase (MAPK) signaling pathways, and through epigenetic mechanisms such as DNA methylation and histone acetylation.

scholarly journals Weaning Induced Hepatic Oxidative Stress, Apoptosis, and Aminotransferases through MAPK Signaling Pathways in Piglets

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Zhen Luo ◽  
Wei Zhu ◽  
Qi Guo ◽  
Wenli Luo ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Redox Status ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Control Group ◽  
Hepatic Oxidative Stress ◽  
Mitogen Activated Protein ◽  
D 20 ◽  
Mapk Signaling Pathways

This study investigated the effects of weaning on the hepatic redox status, apoptosis, function, and the mitogen-activated protein kinase (MAPK) signaling pathways during the first week after weaning in piglets. A total of 12 litters of piglets were weaned at d 21 and divided into the weaning group (WG) and the control group (CG). Six piglets from each group were slaughtered at d 0 (d 20, referred to weaning), d 1, d 4, and d 7 after weaning. Results showed that weaning significantly increased the concentrations of hepatic free radicals H2O2and NO, malondialdehyde (MDA), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), while significantly decreasing the inhibitory hydroxyl ability (IHA) and glutathione peroxidase (GSH-Px), and altered the level of superoxide dismutase (SOD). The apoptosis results showed that weaning increased the concentrations of caspase-3, caspase-8, caspase-9 and the ratio of Bax/Bcl-2. In addition, aspartate aminotransferase transaminase (AST) and alanine aminotransferase (ALT) in liver homogenates increased after weaning. The phosphorylated JNK and ERK1/2 increased, while the activated p38 initially decreased and then increased. Our results suggested that weaning increased the hepatic oxidative stress and aminotransferases and initiated apoptosis, which may be related to the activated MAPK pathways in postweaning piglets.

scholarly journals 3, 4-Dihydroxyphenylethanol attenuates cadmium-induced oxidative stress, inflammation and apoptosis in rat heart

2021 ◽  
Vol 18 (4) ◽  
pp. 713-719
Author(s):  
Yan Huang ◽  
Hongsheng Gang ◽  
Bitao Liang ◽  
Ming Li
Keyword(s):  
Oxidative Stress ◽  
Cardiac Tissue ◽  
Troponin I ◽  
Heart Tissue ◽  
Cardiac Markers ◽  
Tnf Α ◽  
Protein Expressions ◽  
Tissue Homogenates ◽  
Induced Apoptosis ◽  
Pro Inflammatory Cytokines

Purpose: To investigate the therapeutic effect of 3, 4-dihydroxyphenylethanol (DOPET) on cadmium (Cd) induced cardiotoxicity in murine model. Methods: Four groups of rats were used in this study (n = 6). The rats were treated with DOPET and Cd for 28 days. Biochemical parameters were determined in plasma and heart tissue homogenates. Results: Cadmium (Cd) significantly increased lipid peroxidation and protein carbonylation. However, DOPET treatment significantly attenuated Cd-induced oxidative stress. Cd intoxication significantly increased cardiac markers {creatine kinase, lactate dehydrogenase (LDH) and cardiac troponin-I} levels in plasma, and reduced the levels of antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase Gpx ,glutathione (GSH) and malndialdehyde (MDA) in heart tissue. These Cdinduced changes in cardiac markers and antioxidants were reversed by DOPET treatment. Cd treatment led to upregulation of protein expressions of pro-inflammatory cytokines (TNF-α and Il-6). However, DOPET supplementation brought about a decrease in the protein expressions of these cytokines. Western blot analysis revealed that Cd induced apoptosis in cardiac tissue, as was evident from alterations in protein expressions of the apoptotic inducers, Bax and cleaved caspase-3, and the anti-apoptotic factor Bcl-2. However, DOPET treatment effectively reversed Cd-induced apoptosis. Conclusion: These results indicate that DOPET exerts cardio-protective effect against Cd-induced toxicity via antioxidant, anti-inflammatory and anti-apoptotic mechanisms.

scholarly journals Effects of enalapril and paricalcitol treatment on diabetic nephropathy and renal expressions of TNF-α, P53, Caspase-3 and Bcl-2 in STZ-induced diabetic rats

2019 ◽  
Author(s):  
Osama M. Ahmed ◽  
Tarek M. Ali ◽  
Mohamed A. Abdel Gaid ◽  
Ahmed A. Elberry
Keyword(s):  
Oxidative Stress ◽  
Wistar Rats ◽  
Antioxidant Defense ◽  
Caspase 3 ◽  
Enzyme Inhibitor ◽  
Elevated Serum ◽  
Antioxidant Defense System ◽  
Diabetic Rats ◽  
Defense System ◽  
Tnf Α

AbstractThis study aimed to assess the renopreventive effect of the angiotensin converting enzyme inhibitor (ACEI), enalapril, and/or vitamin D receptor (VDR) activator, paricalcitol, on streptozotocin (STZ) diabetes-induced nephropathy and to elucidate the mechanisms of action through investigation of the effects on renal oxidative stress, antioxidant defense system and expressions of TNF-α, P53, caspase-3, and Bcl-2. Diabetes mellitus was induced in fasting male Wistar rats by single intraperitoneal injection of STZ (45 mg /kg b.w.) dissolved in citrate buffer pH 4.5. Ten days after STZ injection, the diabetic rats were treated with enalapril (25 mg/l of drinking water) and/or paricalcitol (8 µg/kg b.w.per os) dissolved in 5% DMSO daily for 4 weeks. The obtained data revealed that the treatment of diabetic Wistar rats with enalapril and/or paricalcitol led to a significant decrease in the elevated serum urea, uric acid, creatinine and sodium, potassium levels; thereby reflecting improvement of the impaired kidney function. The deteriorated kidney lipid peroxidation, GSH content and GST and catalase activities in diabetic rats were significantly ameliorated as a result of treatment with enalapril and/or paricalcitol. The elevated fasting and post-prandial serum glucose levels and the lowered serum insulin and C-peptide levels were also improved. Moreover, the treatment of diabetic rats successfully prevented the diabetes-induced histopathological deleterious changes of kidney and islets of Langerhans of pancreas. In association, the immunohistochemically detected pro-inflammatory cytokine TNF-α and apoptotic mediators P53 and caspase-3 were remarkably decreased in kidney of diabetic rats as a result of treatment, while the expression of anti-apoptotic protein Bcl-2 was increased. Based on these findings, it can be concluded that enalapril and paricalcitol can prevent STZ diabetes-induced nephropathy though amelioration of the glycemic state and antioxidant defense system together with the suppression of oxidative stress, inflammation and apoptosis.

scholarly journals Juglanin alleviates myocardial injury in rats with acute myocardial infarction through modulating MAPK signaling pathway

2021 ◽  
Vol 13 (3) ◽  
pp. 116-122
Author(s):  
Jing Sun ◽  
Lei Song
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Signaling Pathway ◽  
Myocardial Injury ◽  
Morphological Changes ◽  
Mapk Signaling ◽  
Protective Role ◽  
Mitogen Activated Protein Kinase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α

The aim of this study was to investigate the protective role of Juglanin in rats suffering from acute myocardial infarction (AMI). Male Sprague–Dawley (SD) mice were used to construct the AMI model. Hematoxylin and Eosin staining was used to observe the morphological changes of cardiomyocytes. Changes in lactate dehydro-genase (LDH), caspase-3 and caspase-9 were measured using commercial kits. Enzyme-linked immunosorbent assay was used to measure the serum level of creatine kinase myocardial band (CK-MB), Interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), IL-10 and IL-1β. Protein expression and phosphorylation were determined by Western blotting test. The morphology of cardiomyocytes suffered great changes because of AMI, which included focal myocardial necrosis, severe inflammatory cell infiltration, and myocardial fiber dissolution, disorder, and partial rupture. The morphological changes in cardiomyocytes were significantly ameliorated through treatment with Juglanin (10 mg/kg and 30 mg/kg). Increment of serum CK-MB, LDH, IL-6, TNF-α, IL-10 and IL-1β was reduced in AMI rats treated with 10-mg/kg and 30-mg/kg Juglanin. Cell apoptosis was also inhibited by Juglanin treatment. AMI-induced phosphorylation of p38, extracellular signal-regulated kinase (p-ERK) and c-Jun N-terminal kinase (p-JNK) was suppressed through treatment with Juglanin. This study demonstrated that Juglanin alleviated myocardial injury in rats because of AMI through inactivation of mitogen-activated protein kinase signaling pathway, thus indicating a protective role in rat AMI model.

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