Protective role of Salvia miltiorrhiza Polysaccharides on Florfenicol Induced Oxidative and Apoptotic Injury of Liver in Broilers

2021 ◽  
Author(s):  
Xiao Wang ◽  
Yuqing Cui ◽  
Chao Han ◽  
Yumeng Geng ◽  
Di Zhang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Liver Injury ◽  
Protein Expression ◽  
Liver Tissue ◽  
Salvia Miltiorrhiza ◽  
Protective Role ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Mrna And Protein Expression ◽  
Liver Tissues

Abstract Salvia miltiorrhiza Polysaccharides (SMPs) can alleviate liver injury in mice, but there are few reports on liver injury of broilers, especially the liver injury caused by antibiotics. To explore the hepatoprotective effects of SMPs against florfenicol (FFC) induced broilers liver injury, the broilers were treated with FFC and SMPs. The results showed SMPs could significantly inhibit the decrease of weight gain and the increase of liver index induced by FFC (P < 0.05). SMPs could significantly reduce the contents of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) in serum and the malondialdehyde (MDA), nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in liver tissues (P < 0.05), also significantly increased the content of total protein (TP) in serum and superoxide dismutase (SOD), catalase (CAT) in liver tissues (P < 0.05). QPCR and western bolt results showed that SMPs significantly increased the mRNA and protein expression of cytochrome P4501A1 (CYP1A1), cytochrome P4502H1 (CYP2H1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone-1 (NQO-1) in liver tissue, also significantly reduced the rate of hepatocyte apoptosis and the mRNA and protein expression of p53, cytochrome-C (CytC), caspase-3 in liver tissue (P < 0.05). The results demonstrated that SMPs can inhibit the oxidative stress in hepatocytes by regulating the related proteins in Nrf2 pathway, thereby reducing the apoptosis of hepatocytes, and protecting liver injury.

scholarly journals Galangin Activates Nrf2 Signaling and Attenuates Oxidative Damage, Inflammation, and Apoptosis in a Rat Model of Cyclophosphamide-Induced Hepatotoxicity

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 346 ◽  
Author(s):  
Aladaileh ◽  
Abukhalil ◽  
Saghir ◽  
Hanieh ◽  
Alfwuaires ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Liver Injury ◽  
Oxidative Damage ◽  
Biological Activities ◽  
B Cell Lymphoma ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Quinone Acceptor

Cyclophosphamide (CP) is a widely used chemotherapeutic agent; however, its clinical application is limited because of its multi-organ toxicity. Galangin (Gal) is a bioactive flavonoid with promising biological activities. This study investigated the hepatoprotective effect of Gal in CP-induced rats. Rats received Gal (15, 30 and 60 mg/kg/day) for 15 days followed by a single dose of CP at day 16. Cyclophosphamide triggered liver injury characterized by elevated serum transaminases, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and histopathological manifestations. Increased hepatic reactive oxygen species, malondialdehyde, nitric oxide, and oxidative DNA damage along with declined glutathione and antioxidant enzymes were demonstrated in CP-administered rats. CP provoked hepatic nuclear factor-kappaB (NF-κB) phosphorylation and increased mRNA abundance of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) both expression and serum levels. Gal prevented CP-induced liver injury, boosted antioxidants and suppressed oxidative stress, DNA damage, NF-κB phosphorylation and pro-inflammatory mediators. Gal diminished Bax and caspase-3, and increased B-cell lymphoma-2 (Bcl-2) in liver of CP-administered rats. In addition, Gal increased peroxisome proliferator-activated receptor gamma (PPARγ) expression and activated hepatic nuclear factor erythroid 2-related factor 2 (Nrf2) signaling showed by the increase in Nrf2, NAD(P)H: quinone acceptor oxidoreductase-1 (NQO-1) and heme oxygenase 1 (HO-1) in CP-administered rats. These findings suggest that Gal prevents CP hepatotoxicity through activation of Nrf2/HO-1 signaling and attenuation of oxidative damage, inflammation and cell death. Therefore, Gal might represent a promising adjuvant therapy to prevent hepatotoxicity in patients on CP treatment.

scholarly journals Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 976
Author(s):  
Chongshan Dai ◽  
Hui Li ◽  
Yang Wang ◽  
Shusheng Tang ◽  
Tony Velkov ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Protective Effect ◽  
Molecular Mechanisms ◽  
Acute Liver Injury ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Liver Tissues

This study investigates the protective effect of baicalein on carbon tetrachloride (CCl4)-induced acute liver injury and the underlying molecular mechanisms. Mice were orally administrated baicalein at 25 and 100 mg/kg/day for 7 consecutive days or ferrostatin-1 (Fer-1) at 10 mg/kg was i.p. injected in mice at 2 and 24 h prior to CCl4 injection or the vehicle. Our results showed that baicalein or Fer-1 supplementation significantly attenuated CCl4 exposure-induced elevations of serum alanine aminotransferase and aspartate aminotransferase, and malondialdehyde levels in the liver tissues and unregulated glutathione levels. Baicalein treatment inhibited the nuclear factor kappa-B (NF-κB) pathway, activated the erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway in liver tissues, and markedly improved CCl4-induced apoptosis, inflammation and ferroptosis in liver tissues exposed with CCl4. In vitro, baicalein treatment improved CCl4 -induced decreases of cell viabilities and knockdown of Nrf2 and arachidonate 12-lipoxygenase (ALOX12) genes partly abolished the protective effect of baicalein on CCl4 -induced cytotoxicity in HepG2 cells. In conclusion, our results reveal that baicalein supplementation ameliorates CCl4-induced acute liver injury in mice by upregulating the antioxidant defense pathways and downregulating oxidative stress, apoptosis, inflammation and ferroptosis, which involved the activation of Nrf2 pathway and the inhibition of ALOX12 and NF-κB pathways.

scholarly journals Protective Effects of Taraxasterol against Ethanol-Induced Liver Injury by Regulating CYP2E1/Nrf2/HO-1 and NF-κB Signaling Pathways in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Lu Xu ◽  
Yifan Yu ◽  
Rui Sang ◽  
Jinxia Li ◽  
Bingjie Ge ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathways ◽  
Heme Oxygenase 1 ◽  
Intragastric Administration ◽  
Related Factor ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Histopathological Changes ◽  
Liver Index ◽  
Liver Tissues

Taraxasterol, a pentacyclic-triterpene compound, is one of the main active components isolated from the traditional Chinese medicinal herb Taraxacum. The objective of this study is to evaluate the protective effects of taraxasterol and its possible underlying mechanisms against ethanol-induced liver injury in mice. ICR mice were fed with Lieber-DeCarli diet containing 5% ethanol for 10 d and then challenged with a single dose of 20% ethanol (5 g/kg BW) by intragastric administration. The mice were intragastrically treated daily with taraxasterol (2.5, 5, and 10 mg/kg). Tiopronin was used as a positive control. The liver index was calculated, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in sera were detected. The contents of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) and the activity of superoxide dismutase (SOD) in the livers were measured. The histopathological changes of liver tissues were observed by hematoxylin and eosin (H&E) staining. The protein expression levels of hepatic cytochrome P450 2E1 (CYP2E1), nuclear factor erythroid 2-related factor 2 (Nrf2), antioxidant protein heme oxygenase-1 (HO-1), and nuclear factor-kappa B (NF-κB) signaling pathway in liver tissues were detected by immunohistochemistry and Western blot methods. Taraxasterol significantly reduced the ethanol-induced increases of liver index, ALT, AST, and TG levels in sera and TG and MDA contents in the livers and hepatic ROS production and suppressed the ethanol-induced decreases of hepatic GSH level and SOD activity. Taraxasterol also significantly inhibited the secretion of proinflammatory cytokines TNF-α and IL-6 induced by ethanol. In addition, taraxasterol improved the liver histopathological changes in mice with ethanol-induced liver injury. Further studies revealed that taraxasterol significantly inhibited the ethanol-induced upregulation of CYP2E1, increased the ethanol-induced downregulation of Nrf2 and HO-1, and inhibited the degradation of inhibitory kappa Bα (IκBα) and the expression level of NF-κB p65 in liver tissues of ethanol-induced mice. These findings suggest that taraxasterol possesses the potential protective effects against ethanol-induced liver injury in mice by exerting antioxidative stress and anti-inflammatory response via CYP2E1/Nrf2/HO-1 and NF-κB signaling pathways.

Pistacia chinensisInhibits NO Production and Upregulates HO-1 Induction via PI-3K/Akt Pathway in LPS Stimulated Macrophage Cells

2012 ◽  
Vol 40 (05) ◽  
pp. 1085-1097 ◽  
Author(s):  
Taddesse Yayeh ◽  
Mei Hong ◽  
Qi Jia ◽  
Young-Chul Lee ◽  
Hyun-Jin Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Expression ◽  
Raw264.7 Cells ◽  
Akt Pathway ◽  
Heme Oxygenase 1 ◽  
No Production ◽  
Related Factor ◽  
Phenolic Lipids ◽  
Cox 2 ◽  
Pre Treatment

Pistacia chinensis has been used for various purposes in China including as an understock for grafting Pistacia vera. However, little attention was given to its health promoting effects. Therefore, in this study, we investigated the effect of Pistacia chinensis methanolic extract (PCME) containing resorcinol class of phenolic lipids on pro-inflammatory mediators and heme oxygenase-1(HO-1) in lipopolysaccharide stimulated RAW264.7 cells. While PCME (2.5–10 μg/ml) inhibited mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interleukin (IL)-6, it up-regulated HO-1 expression. Likewise, PCME inhibited iNOS protein expression, but not COX-2, and reduced nitric oxide (NO) release. Moreover, Phosphorylated c-Jun N-terminal Kinase (JNK) was attenuated dose-dependently in PCME pre-treated RAW264.7 cells. In addition, PCME up-regulated HO-1 protein expression was diminished by pre-treatment of PI-3K inhibitor. Furthermore, nuclear factor erythroid 2 related factor 2 (Nrf2) repressor was attenuated time-dependently during PCME treatment. Taken together, our study showed (for the first time) that PCME inhibited NO production and up-regulated HO-1 induction via PI-3K/Akt pathway, suggesting the role of Pistacia chinensis as potential sources of anti-inflammatory and antioxidant natural compounds.

scholarly journals Heme-Mediated Activation of the Nrf2/HO-1 Axis Attenuates Calcification of Valve Interstitial Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 427
Author(s):  
Enikő Balogh ◽  
Arpan Chowdhury ◽  
Haneen Ababneh ◽  
Dávid Máté Csiki ◽  
Andrea Tóth ◽  
...  
Keyword(s):  
Target Gene ◽  
Interstitial Cells ◽  
Protective Role ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Valvular Interstitial Cells ◽  
Aortic Valves ◽  
Antioxidant Genes ◽  
Valve Interstitial Cells ◽  
Nrf2 Target Gene

Calcific aortic valve stenosis (CAVS) is a heart disease characterized by the progressive fibro-calcific remodeling of the aortic valves, an actively regulated process with the involvement of the reactive oxygen species-mediated differentiation of valvular interstitial cells (VICs) into osteoblast-like cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of a variety of antioxidant genes, and plays a protective role in valve calcification. Heme oxygenase-1 (HO-1), an Nrf2-target gene, is upregulated in human calcified aortic valves. Therefore, we investigated the effect of Nrf2/HO-1 axis in VIC calcification. We induced osteogenic differentiation of human VICs with elevated phosphate and calcium-containing osteogenic medium (OM) in the presence of heme. Heme inhibited Ca deposition and OM-induced increase in alkaline phosphatase and osteocalcin (OCN) expression. Heme induced Nrf2 and HO-1 expression in VICs. Heme lost its anti-calcification potential when we blocked transcriptional activity Nrf2 or enzyme activity of HO-1. The heme catabolism products bilirubin, carbon monoxide, and iron, and also ferritin inhibited OM-induced Ca deposition and OCN expression in VICs. This study suggests that heme-mediated activation of the Nrf2/HO-1 pathway inhibits the calcification of VICs. The anti-calcification effect of heme is attributed to the end products of HO-1-catalyzed heme degradation and ferritin.

scholarly journals Pharmacological Targeting of Heme Oxygenase-1 in Osteoarthritis

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 419
Author(s):  
Yohei Sanada ◽  
Sho Joseph Ozaki Tan ◽  
Nobuo Adachi ◽  
Shigeru Miyaki
Keyword(s):  
Heme Oxygenase ◽  
Redox Homeostasis ◽  
Synovial Fibroblasts ◽  
Protective Role ◽  
Joint Disease ◽  
Heme Oxygenase 1 ◽  
Transcriptional Level ◽  
Related Factor ◽  
Mobility Limitations ◽  
Therapeutic Implications

Osteoarthritis (OA) is a common aging-associated disease that clinically manifests as joint pain, mobility limitations, and compromised quality of life. Today, OA treatment is limited to pain management and joint arthroplasty at the later stages of disease progression. OA pathogenesis is predominantly mediated by oxidative damage to joint cartilage extracellular matrix and local cells such as chondrocytes, osteoclasts, osteoblasts, and synovial fibroblasts. Under normal conditions, cells prevent the accumulation of reactive oxygen species (ROS) under oxidatively stressful conditions through their adaptive cytoprotective mechanisms. Heme oxygenase-1 (HO-1) is an iron-dependent cytoprotective enzyme that functions as the inducible form of HO. HO-1 and its metabolites carbon monoxide and biliverdin contribute towards the maintenance of redox homeostasis. HO-1 expression is primarily regulated at the transcriptional level through transcriptional factor nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), specificity protein 1 (Sp1), transcriptional repressor BTB-and-CNC homology 1 (Bach1), and epigenetic regulation. Several studies report that HO-1 expression can be regulated using various antioxidative factors and chemical compounds, suggesting therapeutic implications in OA pathogenesis as well as in the wider context of joint disease. Here, we review the protective role of HO-1 in OA with a focus on the regulatory mechanisms that mediate HO-1 activity.

scholarly journals Anti-Inflammatory and Antioxidant Effects of Soroseris hirsuta Extract by regulating iNOS/NF-κB and NRF2/HO-1 Pathways in Murine Macrophage RAW 264.7 Cells

2021 ◽  
Vol 11 (10) ◽  
pp. 4711
Author(s):  
Woo Jin Lee ◽  
Wan Yi Li ◽  
Sang Woo Lee ◽  
Sung Keun Jung
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Antioxidant Properties ◽  
Raw 264.7 Cells ◽  
Heme Oxygenase 1 ◽  
Raw 264.7 ◽  
Related Factor ◽  
Iκb Kinase ◽  
Anti Inflammatory ◽  
Antioxidant Effects

Until now, the physiological effects of Soroseris hirsuta were primarily unknown. Here we have evaluated the anti-inflammatory and antioxidant effects of Soroseris hirsuta extract (SHE) on lipopolysaccharide (LPS)-activated murine macrophages RAW 264.7 cells. SHE inhibited nitric oxide expression and inducible nitric oxide synthase expression in RAW 264.7 cells treated with LPS. Moreover, SHE suppressed LPS-induced phosphorylation of IκB kinase, inhibitor of kappa B, p65, p38, and c-JUN N-terminal kinase. Western blot and immunofluorescence analyses showed that SHE suppressed p65 nuclear translocation induced by LPS. Furthermore, SHE inhibited the reactive oxygen species in LPS-treated RAW 264.7 cells. SHE significantly increased heme oxygenase-1 expression and the nuclear translocation of nuclear factor erythroid 2-related factor 2. SHE suppressed LPS-induced interleukin-1β mRNA expression in RAW 264.7 cells. Thus, SHE is a promising nutraceutical as it displays anti-inflammatory and antioxidant properties.

scholarly journals Hepatoprotective Effect of Polysaccharides Isolated from Dendrobium officinale against Acetaminophen-Induced Liver Injury in Mice via Regulation of the Nrf2-Keap1 Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Guosheng Lin ◽  
Dandan Luo ◽  
Jingjing Liu ◽  
Xiaoli Wu ◽  
Jinfen Chen ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Hepatoprotective Effect ◽  
Dendrobium Officinale ◽  
Regulatory Subunit ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Glutamate Cysteine Ligase ◽  
Nrf2 Signaling Pathway

The effect of polysaccharides isolated from Dendrobium officinale (DOP) on acetaminophen- (APAP-) induced hepatotoxicity and the underlying mechanisms involved are investigated. Male Institute of Cancer Research (ICR) mice were randomly assigned to six groups: (1) control, (2) vehicle (APAP, 230 mg/kg), (3) N-acetylcysteine (100 mg/kg), (4) 50 mg/kg DOP, (5) 100 mg/kg DOP, and (6) 200 mg/kg DOP. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum and glutathione (GSH), malondialdehyde (MDA), catalase (CAT), total antioxidant capacity (T-AOC), myeloperoxidase (MPO), and reactive oxygen species (ROS) levels in the liver were determined after the death of the mice. The histological examination of the liver was also performed. The effect of DOP on the Kelch-like ECH-associated protein 1- (Keap1-) nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was evaluated using Western blot analysis and real-time polymerase chain reaction (PCR). The results showed that DOP treatment significantly alleviated the hepatic injury. The decrease in ALT and AST levels in the serum and ROS, MDA, and MPO contents in the liver, as well as the increases in GSH, CAT, and T-AOC in the liver, were observed after DOP treatment. DOP treatment significantly induced the dissociation of Nrf2 from the Nrf2−Keap1 complex and promoted the Nrf2 nuclear translocation. Subsequently, DOP-mediated Nrf2 activation triggered the transcription and expressions of the glutamate–cysteine ligase catalytic (GCLC) subunit, glutamate–cysteine ligase regulatory subunit (GCLM), heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1) in APAP-treated mice. The present study revealed that DOP treatment exerted potentially hepatoprotective effects against APAP-induced liver injury. Further investigation about mechanisms indicated that DOP exerted the hepatoprotective effect by suppressing the oxidative stress and activating the Nrf2−Keap1 signaling pathway.

scholarly journals The Protective Role of Resveratrol against Arsenic Trioxide-Induced Cardiotoxicity

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Weiqian Zhang ◽  
Changming Guo ◽  
Ruifeng Gao ◽  
Ming Ge ◽  
Yanzhu Zhu ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Cardiac Dysfunction ◽  
Oxidative Dna Damage ◽  
Antioxidant Properties ◽  
Reactive Oxygen Species Generation ◽  
Protective Role ◽  
Natural Food ◽  
Heme Oxygenase 1 ◽  
Related Factor

Arsenic trioxide (As2O3) shows substantial anticancer activity in patients with acute promyelocytic leukemia (APL). Unfortunately, limiting the application of this effective agent to APL patients is severe cardiotoxicity. Resveratrol, the natural food-derived polyphenolic compound, is well known for its antioxidant properties and protects the cardiovascular system. But the potential role of resveratrol against As2O3in heart via nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) is unclear. The present study evaluated the effects of pretreatment with resveratrol and As2O3on oxidative stress and cardiac dysfunction in rat. In the present study, resveratrol decreased As2O3-induced reactive oxygen species generation, oxidative DNA damage, and pathological alterations. In addition, cardiac dysfunction parameters, intracellular calcium and arsenic accumulation, glutathione redox ratio, and cAMP deficiency levels were observed in As2O3-treated rats; these changes were attenuated by resveratrol. Furthermore, resveratrol significantly prohibited the downregulation of both Nrf2 and HO-1 gene expressions that were downregulated by As2O3, whereas resveratrol did not alter As2O3-induced nitric oxide formation. Thus, the protective role of resveratrol against As2O3-induced cardiotoxicity is implemented by the maintenance of redox homeostasis (Nrf2-HO-1 pathway) and facilitating arsenic efflux. Our findings suggest coadministration with resveratrol, and As2O3might provide a novel therapeutic strategy for APL.

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