scholarly journals Effects of peroxisome proliferator activated receptors (PPAR)-γ and -α agonists on cochlear protection from oxidative stress

PLoS ONE ◽  
2017 ◽  
Vol 12 (11) ◽  
pp. e0188596 ◽  
Author(s):  
Marijana Sekulic-Jablanovic ◽  
Vesna Petkovic ◽  
Matthew B. Wright ◽  
Krystsina Kucharava ◽  
Nathan Huerzeler ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Peroxisome Proliferator ◽  
Ppar Γ ◽  
Peroxisome Proliferator Activated Receptors

scholarly journals Amelioration of Oxidative Stress and Neuroinflammation by Saroglitazar, A Dual PPARα/γ Agonist in MES Induced Epileptic Rats

2019 ◽  
Vol 12 (04) ◽  
pp. 1985-1991
Author(s):  
Snigdha Rani Panigrahy ◽  
Supriya Pradhan ◽  
Chandra Sekhar Maharana
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Marker ◽  
Immunohistochemical Analysis ◽  
Clonic Seizure ◽  
Peroxisome Proliferator ◽  
Ppar Γ ◽  
Group I ◽  
Cox 2 ◽  
Peroxisome Proliferator Activated Receptors ◽  
Pre Treatment

Oxidative stress and neuroinflammatory process are implicated in pathophysiology of epilepsy as well as epileptogenesis. The α and γ isoform of peroxisome proliferator-activated receptors (PPAR) agonist has been reported to have antioxidant and anti-inflammatory functions. We hypothesized that saroglitazar, a dual PPAR-α and PPAR-γ agonist may ameliorate oxidative stress and neuroinflammatory process in MES induced epileptic rats. A total of 36 rats were randomized to different groups (n=6). Group I served as normal control, while in the remaining groups (group IV, V and VI) animals were pre-treated with saroglitazar for 15 days prior to inducing MES. Group I animals were pre-treated with vehicle and group-III with diazepam (2mg/kg). Epilepsy was induced in rats and time taken for onset of tonic hind limb extension (THLE), duration of THLE, duration of clonic phase and recovery time in seconds were noted. Brain SOD and MDA levels were assessed and immunohistochemical analysis was done to evaluate the expression of inflammatory marker COX-2. Pre-treatment with saroglitazar was effective against tonic clonic seizure in MES treated rats. SOD levels significantly increased and a significant reduction in MDA levels with a remarkable decrease in the uptake of COX-2 antibody were reported. Saroglitazar attenuated MES induced epilepsy and the probable underlying mechanisms are due to the inhibition of oxidative stress and neuroinflammation.

scholarly journals Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
White Adipocyte ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

Role of peroxisome proliferator–activated receptor-gamma activation on visfatin, advanced glycation end products, and renal oxidative stress in obesity-induced type 2 diabetes mellitus

2018 ◽  
Vol 37 (11) ◽  
pp. 1187-1198 ◽  
Author(s):  
A Tabassum ◽  
T Mahboob
Keyword(s):  
Oxidative Stress ◽  
Renal Damage ◽  
Peroxisome Proliferator ◽  
Advanced Glycation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Glycation End Products ◽  
End Products

The present study focused on the role of peroxisome proliferator–activated receptor-gamma (PPAR-γ) activation on renal oxidative damages, serum visfatin, and advanced glycation end products (AGEs) in high-fat diet (HFD)-induced type 2 diabetes mellitus. Following the institutional animal ethics committee guidelines, Wistar rats were categorized into five groups: group 1: fed on a normal rat diet; group 2: HFD-induced obese rats (HFD for 8 weeks); group 3: HFD-fed rats treated with rosiglitazone (RSG; 3 mg/kg orally for 7 days); group 4: T2DM rats induced by HFD and low dose of streptozotocin (i.p. 35 mg/kg); group 5: T2DM rats treated with RSG (3 mg/kg orally for 7 days). Serum levels of AGEs and visfatin, renal damage, and oxidative stress were analyzed. Results showed that HFD-induced obesity and T2DM caused an elevated blood glucose, serum AGEs, visfatin, insulin, urea, creatinine, and tissue malondialdehyde, whereas a decreased catalase and superoxide dismutase activity were observed. The PPAR-γ activation via agonist restored these changes. Our findings suggest that AGEs and visfatin possess an important role in the progression of renal oxidative stress, which can be reduced by the PPAR-γ agonist that impede deleterious effects of HFD and HFD-induced T2DM on renal damage.

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 Beta-sitosterol upregulated paraoxonase-1 via peroxisome proliferator-activated receptor-γ in irradiated rats

2017 ◽  
Vol 95 (6) ◽  
pp. 661-666 ◽  
Author(s):  
Enas Mahmoud Moustafa ◽  
Noura Magdy Thabet
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Enzyme Activities ◽  
Liver Tissue ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Oxidative Stress Marker ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

This study was designed to evaluate the effect of beta-sitosterol (BS) on the peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression role in the activity of paraoxonase (PON-1) enzyme in oxidative stress status of irradiated rats. Animals were exposed to whole body γ-radiation single dose 6 Gy and received BS dose (40 mg·(kg body mass)−1·day−1, orally). In liver tissue, gene expression of PPAR-γ ligand was determined. Oxidative stress marker (malondialdehyde, MDA) and antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT), PON-1, and arylesterase (ARE)) were assayed in serum and liver tissue. Also, serum lipid profile (cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) was measured. In irradiated animals that received BS, expression of PPAR-γ ligand increase significantly associated with increase in PON-1 and ARE enzyme activities. Also, the activities of SOD, CAT enzymes, and HDL-c levels display elevation. By contrast, significant decrease in MDA content, cholesterol, TG, and LDL-c levels were revealed after BS administration. Our findings in this study provide the evidence that BS has radio-protective effect via regulating the gene expression of PPAR-γ, causing an increase in PON-1 and ARE enzyme activities. This action of BS is due to its free radical scavenging properties, antioxidant effect, lowering of cholesterol, and PPAR-γ agonist properties.

Oxidative stress-induced alterations in PPAR-γ and associated mitochondrial destabilization contribute to kidney cell apoptosis

2014 ◽  
Vol 307 (7) ◽  
pp. F814-F822 ◽  
Author(s):  
David M. Small ◽  
Christudas Morais ◽  
Jeff S. Coombes ◽  
Nigel C. Bennett ◽  
David W. Johnson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Cell Viability ◽  
Mitochondrial Biogenesis ◽  
Peroxisome Proliferator ◽  
Western Blots ◽  
Positive Effects ◽  
Ppar Γ ◽  
Mitotracker Red ◽  
And Oxidative Stress

The mechanism(s) underlying renoprotection by peroxisome proliferator-activated receptor (PPAR)-γ agonists in diabetic and nondiabetic kidney disease are not well understood. Mitochondrial dysfunction and oxidative stress contribute to kidney disease. PPAR-γ upregulates proteins required for mitochondrial biogenesis. Our aim was to determine whether PPAR-γ has a role in protecting the kidney proximal tubular epithelium (PTE) against mitochondrial destabilisation and oxidative stress. HK-2 PTE cells were subjected to oxidative stress (0.2–1.0 mM H2O2) for 2 and 18 h and compared with untreated cells for apoptosis, mitosis (morphology/biomarkers), cell viability (MTT), superoxide (dihydroethidium), mitochondrial function (MitoTracker red and JC-1), ATP (luminescence), and mitochondrial ultrastructure. PPAR-γ, phospho-PPAR-γ, PPAR-γ coactivator (PGC)-1α, Parkin (Park2), p62, and light chain (LC)3β were investigated using Western blots. PPAR-γ was modulated using the agonists rosiglitazone, pioglitazone, and troglitazone. Mitochondrial destabilization increased with H2O2 concentration, ATP decreased (2 and 18 h; P < 0.05), Mitotracker red and JC-1 fluorescence indicated loss of mitochondrial membrane potential, and superoxide increased (18 h, P < 0.05). Electron microscopy indicated sparse mitochondria, with disrupted cristae. Mitophagy was evident at 2 h (Park2 and LC3β increased; p62 decreased). Impaired mitophagy was indicated by p62 accumulation at 18 h ( P < 0.05). PPAR-γ expression decreased, phospho-PPAR-γ increased, and PGC-1α decreased (2 h), indicating aberrant PPAR-γ activation and reduced mitochondrial biogenesis. Cell viability decreased (2 and 18 h, P < 0.05). PPAR-γ agonists promoted further apoptosis. In summary, oxidative stress promoted mitochondrial destabilisation in kidney PTE, in association with increased PPAR-γ phosphorylation. PPAR-γ agonists failed to protect PTE. Despite positive effects in other tissues, PPAR-γ activation appears to be detrimental to kidney PTE health when oxidative stress induces damage.

scholarly journals Peroxisome Proliferator-Activated Receptor Expression in Murine Models and Humans with Age-related Macular Degeneration

2009 ◽  
Vol 2 (1) ◽  
pp. 141-148 ◽  
Author(s):  
Alexandra A. Herzlich ◽  
Xiaoyan Ding ◽  
Defen Shen ◽  
Robert J. Ross ◽  
Jingsheng Tuo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Retinal Pigment ◽  
Critical Role ◽  
Receptor Expression ◽  
Age Related Macular Degeneration ◽  
Epithelial Cell Line ◽  
Peroxisome Proliferator ◽  
Ppar Γ ◽  
Age Related

Peroxisome proliferator-activated receptors (PPARs) play a role in oxidative stress and VEGF regulation, which are closely related to age-related macular degeneration (AMD). PPAR γ expression and its downstream molecules were examined in fat-1 mice (transgenic mice that convert n-6 to n-3 fatty acids), Ccl2-/-/Cx3cr1-/- mice (an AMD model), ARPE19 cells (a human retinal pigment epithelial cell line, RPE, a cell type with a critical role in AMD), and human eyes with and without AMD. PPAR α, β, and γ, VEGF and receptors were determined by immunohistochemistry in the mice models, humans, and ARPE19 cells. Transcripts of PPARs, VEGF, MMP-9 and HO-1 were determined by RQ-PCR. PPARs were constitutively expressed in normal neuroretina and RPE of humans and mice. PPAR γ expression was increased in fat-1 and Ccl2-/-/Cx3cr1-/- mice. VEGF was decreased in fat-1 mice but increased in Ccl2-/-/Cx3cr1-/- mice. VEGF receptors were stable. VEGF, MMP9 and HO-1 transcript levels were increased in ARPE19 cells under H2O2 - induced oxidative stress. Human AMD retinas exhibited higher PPAR γ. The findings of increased expression of PPAR γ and its downstream proteins (VEGF, MMP9, and HO-1) in H2O2-treated ARPE19 cells, Ccl2-/-/Cx3cr1-/- mice, and human AMD eyes, but decreased VEGF in fat-1 mice, suggest that PPAR γ may play a role in AMD.

scholarly journals Amelioration of High Fructose Diet-Induced Insulin Resistance, Hyperuricemia, and Liver Oxidative Stress by Combined Use of Selective Agonists of PPAR-α and PPAR-γ in Rats

2020 ◽  
Vol 3 (2) ◽  
pp. 76-86
Author(s):  
Mahmoud M. Farag ◽  
Ehab H. Ashour ◽  
Wessam F. El-Hadidy
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Serum Insulin ◽  
Combined Treatment ◽  
Vehicle Group ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Ppar Γ ◽  
The Metabolic Syndrome ◽  
High Fructose

Background: The use of high-fructose (Fr) corn sweeteners and sucrose in manufactured food has markedly increased recently. This excessive Fr intake has been proposed in the etiology of the metabolic syndrome, which shows an increasing prevalence throughout the world. Objective: In this study, we questioned whether fenofibrate (FF), a peroxisome proliferator-activated receptor (PPAR)-α agonist, and pioglitazone (PG), a PPAR-γ agonist, might be effective in ameliorating the metabolic syndrome in a rat model. Materials and Methods: The metabolic syndrome was induced by feeding rats a high-Fr (60%) diet for 10 weeks. The rats were divided into 5 groups: control group, fed a normal rat chow; Fr + vehicle group; Fr + FF group; Fr + PG group; and Fr + (FF + PG) group (treated with both drugs). Drug or vehicle treatment was given daily for 6 weeks (from weeks 5 to 10). Thereafter, blood and liver samples were obtained for biochemical studies. Results: Rats fed a high-Fr diet developed hyperglycemia, hyperinsulinemia, hyperuricemia, hypertriglyceri­demia, and hypercholesterolemia, and had increased serum alanine aminotransferase, hepatic tumor necrosis factor-α, and malondialdehyde levels but decreases in both glutathione content and superoxide dismutase activity. Rat treatment with FF and/or PG attenuated these alterations. The improvement was greater with the combined treatment than with either drug alone, and normalization of insulin sensitivity was observed only in rats treated with the combination therapy. Conclusion: Acting on the 2 main PPAR subfamilies, the combination of FF and PG provides a more efficacious therapy for modulating the changes in serum insulin, uric acid, and lipids, as well as the accompanying hepatic inflammation and oxidative stress that characterize the Fr-induced metabolic syndrome.

Sign in / Sign up

Export Citation Format

Share Document