scholarly journals PPAR-γ Modulators as Current and Potential Cancer Treatments

2021 ◽  
Vol 11 ◽  
Author(s):  
Tiange Chi ◽  
Mina Wang ◽  
Xu Wang ◽  
Ke Yang ◽  
Feiyu Xie ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Clinical Settings ◽  
Peroxisome Proliferator ◽  
Multiple Cancer ◽  
Cancer Treatments ◽  
Ppar Γ ◽  
Cancer Field ◽  
Potential Applications ◽  
Causes Of Mortality ◽  
Peroxisome Proliferator Activated Receptors

Worldwide, cancer has become one of the leading causes of mortality. Peroxisome Proliferator-Activated Receptors (PPARs) is a family of critical sensors of lipids as well as regulators of diverse metabolic pathways. They are also equipped with the capability to promote eNOS activation, regulate immunity and inflammation response. Aside from the established properties, emerging discoveries are also made in PPAR’s functions in the cancer field. All considerations are given, there exists great potential in PPAR modulators which may hold in the management of cancers. In particular, PPAR-γ, the most expressed subtype in adipose tissues with two isoforms of different tissue distribution, has been proven to be able to inhibit cell proliferation, induce cell cycle termination and apoptosis of multiple cancer cells, promote intercellular adhesion, and cripple the inflamed state of tumor microenvironment, both on transcriptional and protein level. However, despite the multi-functionalities, the safety of PPAR-γ modulators is still of clinical concern in terms of dosage, drug interactions, cancer types and stages, etc. This review aims to consolidate the functions of PPAR-γ, the current and potential applications of PPAR-γ modulators, and the challenges in applying PPAR-γ modulators to cancer treatment, in both laboratory and clinical settings. We sincerely hope to provide a comprehensive perspective on the prospect of PPAR-γ applicability in the field of cancer treatment.

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 PPAR-α Modulators as Current and Potential Cancer Treatments

2021 ◽  
Vol 11 ◽  
Author(s):  
Yan Tan ◽  
Mina Wang ◽  
Ke Yang ◽  
Tiange Chi ◽  
Zehuan Liao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Aerobic Glycolysis ◽  
Nuclear Hormone Receptor ◽  
Cancer Therapies ◽  
Cancer Treatments ◽  
Proliferation And Differentiation ◽  
Potential Applications ◽  
Causes Of Mortality ◽  
Potential Cancer ◽  
Abnormal Cell Proliferation

Cancer is one of the leading causes of mortality worldwide. PPAR modulators may hold great potential for the management of cancer patients. Indeed, PPARs are critical sensors and regulators of lipid, and they are able to promote eNOS activation, regulate immunity and inflammation response, and affect proliferation and differentiation of cancer cells. Cancer, a name given to a group of diseases, is characterized by multiple distinctive biological behaviors, including angiogenesis, abnormal cell proliferation, aerobic glycolysis, inflammation, etc. In the last decade, emerging evidence has shown that PPAR-α, a nuclear hormone receptor, can modulate carcinogenesis via exerting effects on one or several characteristic pathological behaviors of cancer. Therefore, the multi-functional PPAR modulators have substantial promise in various types of cancer therapies. This review aims to consolidate the functions of PPAR-α, as well as discuss the current and potential applications of PPAR-α agonists and antagonists in tackling cancer.

Peroxisome proliferator-activated receptors and cardiovascular remodeling

2005 ◽  
Vol 288 (3) ◽  
pp. H1037-H1043 ◽  
Author(s):  
Ernesto L. Schiffrin
Keyword(s):  
Cardiovascular Disease ◽  
Target Genes ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Fat Cell ◽  
Ppar Γ ◽  
Peroxisome Proliferator Activated Receptors ◽  
Prevention Of Cardiovascular Disease

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that heterodimerize with the retinoid X receptor and then modulate the function of many target genes. Three PPARs are known: α, β/δ, and γ. The better known are PPAR-α and PPAR-γ, which may be activated by different synthetic agonists, although the endogenous ligands are unknown. PPAR-α is involved in fatty acid oxidation and expressed in the liver, kidney, and skeletal muscle, whereas PPAR-γ is involved in fat cell differentiation, lipid storage, and insulin sensitivity. However, both have been shown to be present in variable amounts in cardiovascular tissues, including endothelium, smooth muscle cells, macrophages, and the heart. The activators of PPAR-α (fibrates) and PPAR-γ (thiazolidinediones or glitazones) antagonized the actions of angiotensin II in vivo and in vitro and exerted cardiovascular antioxidant and anti-inflammatory effects. PPAR activators lowered blood pressure, induced favorable effects on the heart, and corrected vascular structure and endothelial dysfunction in several rodent models of hypertension. Activators of PPARs may become therapeutic agents useful in the prevention of cardiovascular disease beyond their effects on carbohydrate and lipid metabolism. Some side effects, such as weight gain, as well as documented aggravation of advanced heart failure through fluid retention by glitazones, may, however, limit their therapeutic application in prevention of cardiovascular disease.

scholarly journals Peroxisome proliferator-activated receptors and thiazolidinediones in diabetic nephropathy

2019 ◽  
Vol 8 (10) ◽  
pp. 2344
Author(s):  
Navneet O. Soni ◽  
Saroja V. Pawar ◽  
Sheetal Kale ◽  
Uday A. Mane ◽  
Pravin U. Bhosale ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diabetic Nephropathy ◽  
Volume Expansion ◽  
Peroxisome Proliferator ◽  
Ppar Γ ◽  
Intracellular Mechanism ◽  
Current Article ◽  
Peroxisome Proliferator Activated Receptors ◽  
Expansion Effect

Diabetic nephropathy is global problem with several drugs into trial without much success the current article highlights the role of thiazolidinedione’s in diabetic nephropathy by scrutinizing and reconnoitring the cellular and intracellular mechanism and shielding action and the role of peroxisome proliferator-activated gamma receptors (PPARγ) receptors. Not only anti-diabetic action but renal protective effect with evidence based study has been highlighted. PPAR γ-is versatile target having numerous benefits and mainly preventing fibrosis in diabetic experimental model and some clinical case report yet, the benefits are not up to mark, since renal failure itself causes volume expansion and the thiazolidinedione’s (TZDs) also preserve salt and water and lead to congestive heart failure which constraints its clinical application. Dual activators and balaglitazone selective PPAR modulator are having upcoming potential for treatment of diabetic nephropathy. Further detail investigation on such drug is needed to explore. However adverse effect like heart failure, osteoporosis and volume expansion effect over-rides the beneficial effect thus limiting its clinical use of currently available TZDs.

scholarly journals Trace Elements, PPARs, and Metabolic Syndrome

2020 ◽  
Vol 21 (7) ◽  
pp. 2612 ◽  
Author(s):  
Yujie Shi ◽  
Yixin Zou ◽  
Ziyue Shen ◽  
Yonghong Xiong ◽  
Wenxiang Zhang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Trace Elements ◽  
Mrna Expression ◽  
High Fat Diet ◽  
Binding Activity ◽  
Peroxisome Proliferator ◽  
Dna Binding Activity ◽  
Ppar Γ ◽  
Peroxisome Proliferator Activated Receptors ◽  
Structure Of Proteins

Metabolic syndrome (MetS) is a constellation of metabolic derangements, including central obesity, insulin resistance, hypertension, glucose intolerance, and dyslipidemia. The pathogenesis of MetS has been intensively studied, and now many factors are recognized to contribute to the development of MetS. Among these, trace elements influence the structure of proteins, enzymes, and complex carbohydrates, and thus an imbalance in trace elements is an independent risk factor for MetS. The molecular link between trace elements and metabolic homeostasis has been established, and peroxisome proliferator-activated receptors (PPARs) have appeared as key regulators bridging these two elements. This is because on one hand, PPARs are actively involved in various metabolic processes, such as abdominal adiposity and insulin sensitivity, and on the other hand, PPARs sensitively respond to changes in trace elements. For example, an iron overload attenuates hepatic mRNA expression of Ppar-α; zinc supplementation is considered to recover the DNA-binding activity of PPAR-α, which is impaired in steatotic mouse liver; selenium administration downregulates mRNA expression of Ppar-γ, thereby improving lipid metabolism and oxidative status in the liver of high-fat diet (HFD)-fed mice. More importantly, PPARs’ expression and activity are under the control of the circadian clock and show a robust 24 h rhythmicity, which might be the reasons for the side effects and the clinical limitations of trace elements targeting PPARs. Taken together, understanding the casual relationships among trace elements, PPARs’ actions, and the pathogenesis of MetS is of great importance. Further studies are required to explore the chronopharmacological effects of trace elements on the diurnal oscillation of PPARs and the consequent development of MetS.

scholarly journals Peroxisome proliferator–activated receptor δ limits the expansion of pathogenic Th cells during central nervous system autoimmunity

2010 ◽  
Vol 207 (8) ◽  
pp. 1599-1608 ◽  
Author(s):  
Shannon E. Dunn ◽  
Roopa Bhat ◽  
Daniel S. Straus ◽  
Raymond A. Sobel ◽  
Robert Axtell ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Autoimmune Inflammation ◽  
Enhanced Expression ◽  
Synthetic Ligand ◽  
Ifn Γ ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator–activated receptors (PPARs; PPAR-α, PPAR-δ, and PPAR-γ) comprise a family of nuclear receptors that sense fatty acid levels and translate this information into altered gene transcription. Previously, it was reported that treatment of mice with a synthetic ligand activator of PPAR-δ, GW0742, ameliorates experimental autoimmune encephalomyelitis (EAE), indicating a possible role for this nuclear receptor in the control of central nervous system (CNS) autoimmune inflammation. We show that mice deficient in PPAR-δ (PPAR-δ−/−) develop a severe inflammatory response during EAE characterized by a striking accumulation of IFN-γ+IL-17A− and IFN-γ+IL-17A+ CD4+ cells in the spinal cord. The preferential expansion of these T helper subsets in the CNS of PPAR-δ−/− mice occurred as a result of a constellation of immune system aberrations that included higher CD4+ cell proliferation, cytokine production, and T-bet expression and enhanced expression of IL-12 family cytokines by myeloid cells. We also show that the effect of PPAR-δ in inhibiting the production of IFN-γ and IL-12 family cytokines is ligand dependent and is observed in both mouse and human immune cells. Collectively, these findings suggest that PPAR-δ serves as an important molecular brake for the control of autoimmune inflammation.

Ligands of the peroxisome proliferator‐activated receptors (PPAR‐γ and PPAR‐α) reduce myocardial infarct size

2002 ◽  
Vol 16 (9) ◽  
pp. 1027-1040 ◽  
Author(s):  
NICOLE S. WAYMAN ◽  
YOSHIYUKI HATTORI ◽  
MICHELLE C. MCDONALD ◽  
HELDER MOTA‐FILIPE ◽  
SALVATORE CUZZOCREA ◽  
...  
Keyword(s):  
Infarct Size ◽  
Myocardial Infarct ◽  
Peroxisome Proliferator ◽  
Myocardial Infarct Size ◽  
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.

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