Hesperidin protects against cyclophosphamide-induced hepatotoxicity by upregulation of PPARγ and abrogation of oxidative stress and inflammation

2014 ◽  
Vol 92 (9) ◽  
pp. 717-724 ◽  
Author(s):  
Ayman M. Mahmoud
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Protective Effect ◽  
Liver Lipid ◽  
Inos Mrna ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Intraperitoneal Dose

The most important reason for the non-approval and withdrawal of drugs by the Food and Drug Administration is hepatotoxicity. Therefore, this study was undertaken to evaluate the protective effects of hesperidin against cyclophosphamide (CYP)-induced hepatotoxicity in Wistar rats. The rats received a single intraperitoneal dose of CYP of 200 mg/kg body mass, followed by treatment with hesperidin, orally, at doses of 25 and 50 mg/kg for 11 consecutive days. CYP induced hepatic damage, as evidenced by the significantly elevated levels of serum pro-inflammatory cytokines, serum transaminases, liver lipid peroxidation, and nitric oxide. As a consequence, there was reduced glutathione content, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, were markedly reduced. In addition, CYP administration induced a considerable downregulation of peroxisome proliferator activated receptor gamma (PPARγ) and upregulation of nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) mRNA expression. Hesperidin, in a dose-dependent manner, rejuvenated the altered markers to an almost normal state. In conclusion, hesperidin showed a potent protective effect against CYP-induced oxidative stress and inflammation leading to hepatotoxicity. The study suggests that hesperidin exerts its protective effect against CYP-induced hepatotoxicity through upregulation of hepatic PPARγ expression and abrogation of inflammation and oxidative stress.

scholarly journals Piperine Alleviates Doxorubicin-Induced Cardiotoxicity via Activating PPAR-γ in Mice

PPAR Research ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Yan ◽  
Si-Chi Xu ◽  
Chun-Yan Kong ◽  
Xiao-Yang Zhou ◽  
Zhou-Yan Bian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Injury ◽  
Inflammatory Factors ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Myocardial Oxidative Stress

Background. Oxidative stress, inflammation and cardiac apoptosis were closely involved in doxorubicin (DOX)-induced cardiac injury. Piperine has been reported to suppress inflammatory response and pyroptosis in macrophages. However, whether piperine could protect the mice against DOX-related cardiac injury remain unclear. This study aimed to investigate whether piperine inhibited DOX-related cardiac injury in mice. Methods. To induce DOX-related acute cardiac injury, mice in DOX group were intraperitoneally injected with a single dose of DOX (15 mg/kg). To investigate the protective effects of piperine, mice were orally treated for 3 weeks with piperine (50 mg/kg, 18:00 every day) beginning two weeks before DOX injection. Results. Piperine treatment significantly alleviated DOX-induced cardiac injury, and improved cardiac function. Piperine also reduced myocardial oxidative stress, inflammation and apoptosis in mice with DOX injection. Piperine also improved cell viability, and reduced oxidative damage and inflammatory factors in cardiomyocytes. We also found that piperine activated peroxisome proliferator-activated receptor-γ (PPAR-γ), and the protective effects of piperine were abolished by the treatment of the PPAR-γ antagonist in vivo and in vitro. Conclusions. Piperine could suppress DOX-related cardiac injury via activation of PPAR-γ in mice.

scholarly journals Protective Effect of PPARγAgonists on Cerebellar Tissues Oxidative Damage in Hypothyroid Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Yousef Baghcheghi ◽  
Farimah Beheshti ◽  
Hossein Salmani ◽  
Mohammad Soukhtanloo ◽  
Mahmoud Hosseini
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Drinking Water ◽  
Oxidative Damage ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Group I ◽  
Biochemical Measurements ◽  
Thiol Content

The aim of the current study was to investigate the effects of peroxisome proliferator-activated receptor gamma (PPARγ) agonists on cerebellar tissues oxidative damage in hypothyroid rats. The animals included seven groups: group I (control), the animals received drinking water; group II, the animals received 0.05% propylthiouracil (PTU) in drinking water; besides PTU, the animals in groups III, IV, V, VI, and VII, were injected with 20 mg/kg vitamin E (Vit E), 10 or 20 mg/kg pioglitazone, and 2 or 4 mg/kg rosiglitazone, respectively. The animals were deeply anesthetized and the cerebellar tissues were removed for biochemical measurements. PTU administration reduced thiol content, superoxide dismutase (SOD), and catalase (CAT) activities in the cerebellar tissues while increasing malondialdehyde (MDA) and nitric oxide (NO) metabolites. Vit E, pioglitazone, and rosiglitazone increased thiol, SOD, and CAT in the cerebellar tissues while reducing MDA and NO metabolites. The results of present study showed that, similar to Vit E, both rosiglitazone and pioglitazone as PPARγagonists exerted protective effects against cerebellar tissues oxidative damage in hypothyroid rats.

The protective effect of daidzein on high glucose-induced oxidative stress in human umbilical vein endothelial cells

2016 ◽  
Vol 71 (1-2) ◽  
pp. 21-28 ◽  
Author(s):  
Mi Hwa Park ◽  
Jae-Won Ju ◽  
Mihyang Kim ◽  
Ji-Sook Han
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Protective Effect ◽  
High Glucose ◽  
Umbilical Vein ◽  
Vascular Complications ◽  
Dependent Manner ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

AbstractEndothelial cell dysfunction is considered a major cause of vascular complications in diabetes. In the present study, we investigated the protective effect of daidzein, a natural isoflavonoid, against high-glucose–induced oxidative damage in human umbilical vein endothelial cells (HUVECs). Treatment with a high concentration of glucose (30 mM) induced oxidative stress in the endothelial cells, against which daidzein protected the cells as demonstrated by significantly increased cell viability. In addition, lipid peroxidation, intracellular reactive oxygen species (ROS) generation, and indirect nitric oxide levels induced by the high glucose treatment were significantly reduced in the presence of daidzein (0.02–0.1 mM) in a dose-dependent manner. High glucose levels induced the overexpression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and NF-κB proteins in HUVECs, which was suppressed by treatment with 0.04 mM daidzein. These findings indicate the potential of daidzein to reduce high glucose-induced oxidative stress.

scholarly journals Roles of NF-κB Activation and Peroxisome Proliferator-Activated Receptor Gamma Inhibition in the Effect of Rifampin on Inducible Nitric Oxide Synthase Transcription in Human Lung Epithelial Cells

2008 ◽  
Vol 53 (4) ◽  
pp. 1539-1545 ◽  
Author(s):  
Yael Yuhas ◽  
Eva Berent ◽  
Regev Cohen ◽  
Shai Ashkenazi
Keyword(s):  
Nitric Oxide ◽  
Human Lung ◽  
Inos Mrna ◽  
No Production ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflammatory Genes ◽  
Lung Epithelial ◽  
Pparγ Expression ◽  
Inducible Nitric Oxide

ABSTRACT Rifampin (rifampicin), an important antibiotic agent and a major drug used for the treatment of tuberculosis, exerts immunomodulatory effects. Previous studies have found that rifampin increases inducible nitric oxide (NO) synthase (iNOS) expression and NO production. The present study investigated the potential mechanism(s) underlying these actions. The incubation of human lung epithelial A549 cells with a cytokine mix (interleukin-1β, tumor necrosis factor alpha, and gamma interferon) induced the expression of iNOS mRNA. The addition of rifampin increased the iNOS level by 1.9 ± 0.3-fold at a dose of 10 μg/ml (P < 0.01) and by 4.0 ± 0.3-fold at a dose of 50 μg/ml (P < 0.001). Rifampin treatment also affected the transcription factors that regulate iNOS mRNA: there was an increased and prolonged degradation of the inhibitory subunit of NF-κB, a corresponding increase in the level of cytokine-induced DNA binding of NF-κB (2.1 ± 0.2-fold), and a decrease in the level of expression of peroxisome proliferator-activated receptor gamma (PPARγ). Specifically, the level of PPARγ expression dropped by 15% in response to cytokine stimulation and by an additional 40% when rifampin was added (P < 0.001). Rifampin had no effect on the activation of mitogen-activated protein kinases or the signal transducer and transcription activator (STAT-1). In conclusion, rifampin augments NO production by upregulating iNOS mRNA. It also increases the level of NF-κB activation and decreases the level of PPARγ expression. The increases in the levels of NF-κB activation and NO production probably contribute to the therapeutic effects of rifampin. However, given the role of NF-κB in upregulating many inflammatory genes and the roles of PPARγ in downregulating inflammatory genes and in lipid and glucose metabolism, these findings have implications for potential adverse effects of rifampin in patients with chronic inflammatory diseases and glucose or lipid disorders.

scholarly journals Protective Effects of Peroxisome Proliferator-Activated Receptor-αAgonist, Wy14643, on Hypoxia/Reoxygenation Injury in Primary Rat Hepatocytes

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ke Chen ◽  
Yuan-Hai Li ◽  
Si-Qi Xu ◽  
Sheng-Hong Hu ◽  
Lei Zhang
Keyword(s):  
Rat Hepatocytes ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Protective Effects ◽  
Primary Hepatocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Group A ◽  
Reoxygenation Injury ◽  
Dose Dependent ◽  
Significant Protective Effect

This study investigates the effects and possible mechanism of an agonist of PPARα, Wy14643, on primary hepatocytes subjected to H/R injury in rats. H/R induced a significant increase ALT, AST, MDA in the culture medium and ROS in the hepatocytes. These effects were reversed by pretreatment with Wy14643 in the dose-dependent manner. The activity of SOD and the level of GSH in the hepatocytes were decreased after H/R, which were increased by Wy14643 pretreatment. Moreover, the mRNA expressions of PPARαsignificantly increased in H/R+Wy14643 groups when compared with that in H/R group. A PPARαagonist, Wy14643, exerts significant protective effect against H/R injury in primary hepatocytes via PPARαactivation and attenuating oxidative stress.

scholarly journals Rosiglitazone Affects Nitric Oxide Synthases and Improves Renal Outcome in a Rat Model of Severe Ischemia/Reperfusion Injury

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Boris Betz ◽  
Reinhard Schneider ◽  
Tobias Kress ◽  
Martin Alexander Schick ◽  
Christoph Wanner ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
No Synthase ◽  
Renal Ischemia ◽  
Renal Outcome ◽  
Inos Mrna ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Morphological Alterations

Background.Nitric oxide (NO)-signal transduction plays an important role in renal ischemia/reperfusion (I/R) injury. NO produced by endothelial NO-synthase (eNOS) has protective functions whereas NO from inducible NO-synthase (iNOS) induces impairment. Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor (PPAR)-γagonist exerted beneficial effects after renal I/R injury, so we investigated whether this might be causally linked with NOS imbalance.Methods.RGZ (5 mg/kg) was administered i.p. to SD-rats (f) subjected to bilateral renal ischemia (60 min). Following 24 h of reperfusion, inulin- and PAH-clearance as well as PAH-net secretion were determined. Morphological alterations were graded by histopathological scoring. Plasma NOx-production was measured. eNOS and iNOS expression was analyzed by qPCR. Cleaved caspase 3 (CC3) was determined as an apoptosis indicator and ED1 as a marker of macrophage infiltration in renal tissue.Results.RGZ improves renal function after renal I/R injury (PAH-/inulin-clearance, PAH-net secretion) and reduces histomorphological injury. Additionally, RGZ reduces NOxplasma levels, ED-1 positive cell infiltration and CC3 expression. iNOS-mRNA is reduced whereas eNOS-mRNA is increased by RGZ.Conclusion.RGZ has protective properties after severe renal I/R injury. Alterations of the NO pathway regarding eNOS and iNOS could be an explanation of the underlying mechanism of RGZ protection in renal I/R injury.

scholarly journals SIRT3-dependent mitochondrial oxidative stress in sodium fluoride-induced hepatotoxicity and salvage by melatonin

2017 ◽  
Author(s):  
Chao Song ◽  
Jiamin Zhao ◽  
Jingcheng Zhang ◽  
Tingchao Mao ◽  
Beibei Fu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Binding Activity ◽  
Daily Injection ◽  
Mechanistic Study ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor

AbstractOxidative stress induced by fluoride (F) is associated with fluorosis formation, but the underlying molecular mechanism remains unclear. In this study, Melatonin pretreatment suppressed F-induced hepatocyte injury in HepG2 cells. Melatonin increases the activity of superoxide dismutase (SOD2) by enhancing sirtuin 3 (SIRT3)-mediated deacetylation and promotes SOD2 gene expression via SIRT3-regulated DNA-binding activity of forkhead box O3 (FoxO3a), indicating that melatonin markedly enhanced mROS scavenging in F-exposed HepG2 cells. Notably, melatonin activated the peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α). PGC-1α interacted with the estrogen-related receptor alpha (ERRα) bound to the SIRT3 promoter, where it functions as a transcription factor to regulate SIRT3 expression. Furthermore, daily injection of melatonin for 30 days inhibited F-induced oxidative stress in mice liver, leading to improvement of liver function. Mechanistic study revealed that the protective effects of melatonin were associated with down-regulation of JNK1/2 phosphorylation in vitro and in vivo. Collectively, our data suggest a novel role of melatonin in preventing F-induced oxidative stress through activation of the SIRT3 pathway.

scholarly journals MG53 Protects against Sepsis-Induced Myocardial Dysfunction by Upregulating Peroxisome Proliferator-Activated Receptor-α

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Xue Han ◽  
Daili Chen ◽  
Ning Liufu ◽  
Fengtao Ji ◽  
Qingshi Zeng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Function ◽  
Myocardial Dysfunction ◽  
Cecal Ligation ◽  
Underlying Mechanism ◽  
Cardiomyocyte Apoptosis ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Myocardial Oxidative Stress

Background. The heart is one of the most commonly affected organs during sepsis. Mitsugumin-53 (MG53) has attracted attention in research due to its cardioprotective function. However, the role of MG53 in sepsis-induced myocardial dysfunction (SIMD) remains unknown. The purpose of this study was to explore the underlying mechanism of MG53 in SIMD and investigate its potential relationship with peroxisome proliferator-activated receptor-α (PPARα). Methods. The cecal ligation and puncture (CLP) model was created to induce SIMD in rats. Protein levels of MG53 and PPARα, cardiac function, cardiomyocyte injury, myocardial oxidative stress and inflammatory indicators, and cardiomyocyte apoptosis were measured at 18 h after CLP. The effects of MG53 on PPARα in SIMD were investigated via preconditioning recombinant human MG53 (rhMG53) and PPARα antagonist GW6471. Results. The expression of MG53 and PPARα sharply decreased in the myocardium at 18 h after CLP. Compared with the sham group, cardiac function was significantly depressed, which was associated with the destructed myocardium, upregulated oxidative stress indicators and proinflammatory cytokines, and excessive cardiomyocyte apoptosis in the CLP group. Supplementation with rhMG53 enhanced myocardial MG53, increased the survival rate with improved cardiac function, and reduced oxidative stress, inflammation, and myocardial apoptosis, which were associated with PPARα upregulation. Pretreatment with GW6471 abolished the abovementioned protective effects induced by MG53. Conclusions. Both MG53 and PPARα were downregulated after sepsis shock. MG53 supplement protects the heart against SIMD by upregulating PPARα expression. Our results provide a new treatment strategy for SIMD.

scholarly journals Activating the PGC-1α/TERT Pathway by Catalpol Ameliorates Atherosclerosis via Modulating ROS Production, DNA Damage, and Telomere Function: Implications on Mitochondria and Telomere Link

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Yukun Zhang ◽  
Changyuan Wang ◽  
Yue Jin ◽  
Qining Yang ◽  
Qiang Meng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Rehmannia Glutinosa ◽  
Iridoid Glucoside ◽  
Telomere Shortening ◽  
Peroxisome Proliferator Activated Receptor ◽  
Telomere Function ◽  
Luciferase Activity Assay

Catalpol, an iridoid glucoside, has been found present in large quantities in the root of Rehmannia glutinosa L. and showed a strong antioxidant capacity in the previous study. In the present work, the protective effect of catalpol against AS via inhibiting oxidative stress, DNA damage, and telomere shortening was found in LDLr−/− mice. This study also shows that activation of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)/telomerase reverse transcriptase (TERT) pathway, which is the new link between mitochondria and telomere, was involved in the protective effects of catalpol. Further, by using PGC-1α or TERT siRNA in oxLDL-treated macrophages, it is proved that catalpol reduced oxidative stress, telomere function, and related DNA damage at least partly through activating the PGC-1α/TERT pathway. Moreover, dual luciferase activity assay-validated catalpol directly enhanced PGC-1α promoter activity. In conclusion, our study revealed that the PGC-1α/TERT pathway might be a possible therapeutic target in AS and catalpol has highly favorable characteristics for the treatment of AS via modulating this pathway.

Sign in / Sign up

Export Citation Format

Share Document