The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2)

2016 ◽  
Vol 35 (12) ◽  
pp. 1252-1263 ◽  
Author(s):  
SS Palabiyik ◽  
E Karakus ◽  
Z Halici ◽  
E Cadirci ◽  
Y Bayir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Folk Medicine ◽  
Hepatoprotective Activity ◽  
High Dose ◽  
Protective Effects ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

Rhizophora Mucronata Lam. (Mangrove) Bark Extract Prevents Ethanol-induced Liver Injury, Oxidative Stress and Apoptosis in Swiss Albino Mice

2021 ◽  
Author(s):  
Chitra Jairaman ◽  
Sabine Matou-Nasri ◽  
Zeyad I Alehaideb ◽  
Syed Ali Mohamed Yacoob ◽  
Anuradha Venkataraman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Histopathological Examination ◽  
Bark Extract ◽  
High Dose ◽  
Protective Effects ◽  
Rhizophora Mucronata ◽  
Ethanol Intoxication ◽  
Hepatoprotective Effects

Abstract The bark extract of Rhizophora mucronata (BERM) was recently reported for its prominent in vitro protective effects against liver cell line toxicity caused by various toxicants, including ethanol. Here, we aimed to verify the in vivo hepatoprotective effects of BERM against ethanol intoxication. An oral administration of different concentrations (100, 200, and 400 mg/kg) of BERM prior to high-dose ethanol via intraperitoneal injection was performed in mice. On the 7th day, liver and kidney sections were dissected out for histopathological examination. The ethanol intoxication caused large areas of liver necrosis while the kidneys were not affected. Pre-BERM administration decreased ethanol-induced liver injury, as compared to the mice treated with ethanol alone. In addition, the pre-BERM administration resulted in a decrement in the level of ethanol-induced oxidative stress, revealed by a concomitant increase of GSH and a decrease of MDA hepatic levels. The BERM extract also reversed the ethanol-induced liver injury and hepatotoxicity, characterized by the low detection of TNF-α gene expression level and fragmented DNA, respectively. Altogether, BERM extract exerts antioxidative activities and present promising hepatoprotective effects against ethanol intoxication. The identification of the related bioactive compounds will be of interest for future use at physiological concentrations in ethanol-intoxicated individuals.

Artemisinin improves neurocognitive deficits associated with sepsis by activating the AMPK axis in the microglia.

2020 ◽  
Author(s):  
Shao-Peng Lin ◽  
Jue-Xian Wei ◽  
Shan Ye ◽  
Jiasong Hu ◽  
Jingyi Bu ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Inflammatory Cytokines ◽  
Nuclear Translocation ◽  
Neuronal Damage ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Neurocognitive Deficits ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Background and purpose: Artemisinin has been in use as an anti-malarial drug for almost half a century in the world. There is growing evidence that artemisinin also possesses potent anti-inflammatory and immunoregulatory properties. However, the efficacy of artemisinin treatment in neurocognitive deficits associated with sepsis remains unknown. Here, we evaluate the possible protective effects and explore the underlying mechanism of artemisinin on cognitive impairment resulting from sepsis.Methods: Male C57BL/6 mice were pretreated with either vehicle or artemisinin, and then injected with LPS to establish an animal model of sepsis. The cognitive function was then assessed using the Morris water maze. Neuronal damage and neuroinflammation in the hippocampus were evaluated by immunohistochemical and ELISA analysis. Additionally, the protective mechanism of artemisinin was determined in vitro.Results: The results showed that artemisinin preconditioning attenuated LPS-induced cognitive impairment, neural damage, and microglial activation in the mouse brain. The in vitro experiment revealed that artemisinin could reduce the production of pro-inflammatory cytokines and suppress the microglial migration in the BV2 microglia cells. Meanwhile, western blot demonstrated that artemisinin suppressed nuclear translocation of nuclear factor kappa-B and the expression of pro-inflammatory cytokines (i.e. tumor necrosis factor alpha, interleukin-6) by activating adenosine monophosphate-activated protein kinaseα1 (AMPKα1) pathway. Furthermore, knock-down of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin.Conclusion: Artemisinin is a potential therapeutic agent for sepsis-associated neuroinflammation and cognitive impairment, and its effect was probably mediated by the activation of AMPKα1 signalling pathway in microglia.

Pro-inflammatory cytokines reduce human TAFI expression via tristetraprolin-mediated mRNA destabilisation and decreased binding of HuR

2015 ◽  
Vol 114 (08) ◽  
pp. 337-349 ◽  
Author(s):  
Dragana Komnenov ◽  
Corey Scipione ◽  
Zainab Bazzi ◽  
Justin Garabon ◽  
Marlys Koschinsky ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Mediators ◽  
Hepg2 Cells ◽  
Inflammatory Cells ◽  
Gene Encoding ◽  
Protein Levels ◽  
Anti Inflammatory ◽  
Mechanistic Basis ◽  
Pro Inflammatory Cytokines

SummaryThrombin activatable fibrinolysis inhibitor (TAFI) is the zymogen form of a basic carboxypeptidase (TAFIa) with both anti-fibrinolytic and anti-inflammatory properties. The role of TAFI in inflammatory disease is multifaceted and involves modulation both of specific inflammatory mediators as well as of the behaviour of inflammatory cells. Moreover, as suggested by in vitro studies, inflammatory mediators are capable of regulating the expression of CPB2, the gene encoding TAFI. In this study we addressed the hypothesis that decreased TAFI levels observed in inflammation are due to post-transcriptional mechanisms. Treatment of human HepG2 cells with pro-inflammatory cytokines TNFα, IL-6 in combination with IL-1β, or with bacterial lipopolysaccharide (LPS) decreased TAFI protein levels by approximately two-fold over 24 to 48 hours of treatment. Conversely, treatment of HepG2 cells with the anti-inflammatory cytokine IL-10 increased TAFI protein levels by two-fold at both time points. We found that the mechanistic basis for this modulation of TAFI levels involves binding of tristetraprolin (TTP) to the CPB2 3′-UTR, which mediates CPB2 mRNA destabilisation. In this report we also identified that HuR, another ARE-binding protein but one that stabilises transcripts, is capable of binding the CBP2 3’UTR. We found that pro-inflammatory mediators reduce the occupancy of HuR on the CPB2 3’-UTR and that the mutation of the TTP binding site in this context abolishes this effect, although TTP and HuR appear to contact discrete binding sites. Interestingly, all of the mediators tested appear to increase TAFI protein expression in THP-1 macrophages, likewise through effects on CPB2 mRNA stability.

scholarly journals Protective effects of ethanolic extract of Alhagi maurorum roots on renal failure induced by acetaminophen in mice

2021 ◽  
Vol 8 (1) ◽  
pp. 16-22
Author(s):  
Seham I AL-Nafea ◽  
Mohammed O Aljahdali
Keyword(s):  
Oxidative Stress ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Serum Levels ◽  
High Dose ◽  
Root Extract ◽  
Protective Effects ◽  
Oxidative Stress Biomarkers ◽  
Protective Actions ◽  
And Oxidative Stress

The protective actions of ethanol Alhagi maurorum (AM) root ethanol extract on acetaminophen-induced oxidative stress and renal toxicity in mice was evaluated. Forty male SWR strain albino mice aged 8 weeks were grouped into five groups. G1 (n=5): as control. G2 (n=5): administered orally a single dose of acetaminophen (2000mg/kg). G3 (n=10) administrated orally 200 mg/kg of roots ethanol extract for one week then acetaminophen as G2 at 8th day and; G4 (n=10) administrated orally 400 mg/kg of roots ethanol extract for one week then acetaminophen as G2 at 8th day; G5 (n=10) administrated orally 600 mg/kg of roots ethanol extract for one week then acetaminophen as G2 at 8th day. At end of experiments, the mice were killed under anesthesia and blood samples were gathered to preform complete blood test (CBC), serum levels of urea and creatinine and oxidative stress biomarkers as superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) using available Elisa mice kits. Kidneys were removed and histologically examined. Acetaminophen intake significantly elevated WBCs, neutrophils, monocytes, urea and creatinine levels and significantly decreased RBCs, hemoglobin, hematocrit, GSH, SOD and CAT (P <0.05). Treatment with Alhagi maurorum roots extract especially high dose (600 mg/kg) resulted in decreased in WBCs, neutrophils, monocytes, urea and creatinine levels and significantly increased RBCs, hemoglobin, hematocrit, GSH, SOD and CATversusacetaminophen group. Alhagi maurorum root extract treatment similarly decreased renal histological alteration induced by acetaminophen. This study can be utilized as prove of reading that Alhagi maurorum ethanol root extract especially high dose might be administered to prevent renal destruction induced by acetaminophen due to its antioxidant activity

scholarly journals Dihydromyricetin Attenuates Palmitate Acid-Induced Oxidative Stress by promoting Autophagy via SIRT3-ATG4B Signaling in Hepatocytes

2021 ◽  
Author(s):  
Mantian Mi ◽  
Li Huang ◽  
Xianglong Zeng ◽  
Bo Li ◽  
Cong Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Underlying Mechanism ◽  
Protective Effects ◽  
Inhibitory Effects ◽  
Potential Therapeutic Target ◽  
Mitochondrial Ros ◽  
Intracellular Ros ◽  
Protein Expressions ◽  
And Oxidative Stress

Abstract Background Oxidative stress in hepatocytes was an important pathogenesis of nonalcoholic steatohepatitis (NASH). Autophagy was a cellular process that can remove damaged organelles under oxidative stress, and thus presented a potential therapeutic target against NASH. The aim of this work was to investigate whether autophagy participated the protective effects of dihydromyricetin (DHM) on palmitic acid (PA)-induced oxidative stress in hepatocytes and the underlying mechanism. Methods HepG2 cells were pretreated with DHM (20 µM) for 2 h, followed by PA (0.2 mM) treatment for 16 h. The oxidative stress was assessed by the quantification of intracellular reactive oxygen species (ROS), mitochondrial ROS (mtROS), mitochondrial membrane potential (MMP) and mitochondrial ultrastructural analyses. The protein expressions of SIRT3, LC3I/II, P62 and ATG4B, as well as the acetylation of AGT4B were determined by western blotting using HepG2 and HepG2/ ATG4B+/− cells with heterozygous knockout of ATG4B. Results Exposure to PA resulted in increased intracellular ROS and mtROS, decreased MMP and aggravated mitochondrial injury in HepG2 cells, which were notably attenuated by DHM treatment. DHM-induced inhibition of oxidative stress was associated with the induction of autophagy, characterized by upregulated ATG4B and LC3 II as well as downregulated P62 levels. Furthermore, the inhibitory effects of DHM on PA-induced autophagy arrest and oxidative stress were eliminated when pretreated with a SIRT3 inhibitor 3-TYP or conducted in HepG2/ATG4B+/− cells, suggesting that SIRT3 and ATG4B were involved in DHM-induced benefits. Moreover, DHM treatment increased the protein expression of SIRT3 and SIRT3-dependent deacetylation of ATG4B in HepG2 cells. Conclusion Our results demonstrated that DHM attenuated PA-induced oxidative stress in hepatocytes through induction of autophagy, which was mediated through the increased expression of SIRT3 and SIRT3-mediated ATG4B deacetylation following DHM treatment.

scholarly journals Nobiletin Protects Against Diabetes-induced Testicular Injury via Hypophysis-gonadal Axis Up-regulation and Amelioration of Oxidative Stress

2021 ◽  
Author(s):  
Marwa Salah ◽  
Khadiga Ahmed Ismail ◽  
sally mostafa khadrawy
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Caspase 3 ◽  
Androgen Receptors ◽  
Glycosylated Hemoglobin ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
High Dose ◽  
Testicular Injury ◽  
Pro Inflammatory Cytokines

Abstract Background: Testicular injury is one of the most serious problems of Diabetes mellitus. The present study aims to compare the effect of two different doses of nobiletin and the probable mechanisms against diabetes-induced testicular impairment in rats. Methods and Results: Streptozotocin injection was used to induce diabetes. Diabetic rats received nobiletin (10 mg/kg) or (25 mg/kg) daily and orally for 30 days. Diabetic rats displayed a significant elevation in glucose, glycosylated hemoglobin (HbA1c), homeostasis model of insulin resistance (HOMA-IR), and pro-inflammatory cytokines. Levels of serum insulin, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly reduced. Histological changes with positive caspase-3 and decreased Androgen receptors (AR) immunoexpressions were observed in diabetic rats. Both doses of nobiletin improved hyperglycemia, reduced pro-inflammatory cytokines, and augmented insulin, testosterone, LH, and FSH levels. Gene and protein manifestation of LH and FSH receptors and cytochrome P450 17 α-hydroxylase (CYP17A1) was markedly down-regulated in testicular tissues of diabetic group, an effect which was markedly increased with both doses of nobiletin. In addition, both doses significantly reduced lipid peroxidation, and caspase-3 immuno-expression and improved the activity of the antioxidant enzymes and AR in testicular tissues of diabetic group. Conclusion: Both doses showed protective effects against diabetes-induced testicular injury by diminution of oxidative stress, hyperglycemia, inflammation, caspase-3 and up-regulation of the hypophysis-gonadal axis and androgen receptors. The high dose of nobiletin was more effective than the lower dose.

scholarly journals EGCG Attenuates Uric Acid-Induced Inflammatory and Oxidative Stress Responses by Medicating the NOTCH Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Hua Xie ◽  
Jianqin Sun ◽  
Yanqiu Chen ◽  
Min Zong ◽  
Shijie Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Inflammatory Cytokines ◽  
Stress Responses ◽  
Umbilical Vein ◽  
Notch Pathway ◽  
Notch 1 ◽  
Western Blots ◽  
And Oxidative Stress

Background. The aim of this study is to investigate whether (-)-epigallocatechin-3-gallate (EGCG) can prevent the UA-induced inflammatory effect of human umbilical vein endothelial cells (HUVEC) and the involved mechanisms in vitro.Methods. HUVEC were subjected to uric acid (UA) with or without EGCG treatment. RT-PCR and western blots were performed to determine the level of inflammation marker. The antioxidant activity was evaluated by measuring scavenged reactive oxygen species (ROS). Functional studies of the role of Notch-1 in HUVEC lines were performed using RNA interference analyses.Results. UA significantly increased the expressions of IL-6, ICAM-1, TNF-α, and MCP-1 and the production of ROS in HUVEC. Meanwhile, the expression of Notch-1 and its downstream effects significantly increased. Using siRNA, inhibition of Notch-1 signaling significantly impeded the expressions of inflammatory cytokines under UA treatment. Interestingly, EGCG suppressed the expressions of inflammatory cytokines and the generation of ROS. Western blot analysis of Notch-1 showed that EGCG significantly decreased the expressions of inflammatory cytokines through Notch-1 signaling pathways.Conclusions. In summary, our findings indicated that Notch-1 plays an important role in the UA-induced inflammatory response, and the downregulation of Notch-1 by EGCG could be an effective approach to decrease inflammation and oxidative stress induced by UA.

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