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Pioglitazone AND PPAR gamma

Hongbin Jia, Shuangshuang Xu, Qingzhen Liu, Jian Liu, Jianguo Xu, Weiyan Li, Yi Jin, Qing Ji
The molecular mechanisms underlying neuropathic pain have yet to be elucidated. The present study aimed to examine the modulation of neuroimmune activation in the spinal cord by the synthetic peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, pioglitazone (Pio), in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Rats were randomly assigned into four groups: Sham surgery with vehicle, chronic constriction injury with vehicle or Pio (10 mg/kg), and chronic constriction injury with Pio and a PPAR-γ antagonist GW9662 (2 mg/kg)...
October 2016: Experimental and Therapeutic Medicine
J R Anderson, K Mortimer, L Pang, K M Smith, H Bailey, D B Hodgson, D E Shaw, A J Knox, T W Harrison
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a nuclear receptor that modulates inflammation in models of asthma. To determine whether pioglitazone improves measures of asthma control and airway inflammation, we performed a single-center randomized, double-blind, placebo-controlled, parallel-group trial. METHODS: Sixty-eight participants with mild asthma were randomized to 12 weeks pioglitazone (30 mg for 4 weeks, then 45 mg for 8 weeks) or placebo...
2016: PloS One
Yao-Chung Chuang, Tsu-Kung Lin, Ding-I Yang, Jenq-Lin Yang, Chia-Wei Liou, Shang-Der Chen
BACKGROUND: Dynamin-related protein 1 (Drp1) is a mitochondrial fission protein that, upon phosphorylation at serine 616 (p-Drp1(Ser616)), plays a pivotal role in neuronal death after ischemia. In the present study, we hypothesized that peroxisome proliferator-activated receptor-gamma (PPARγ)-dependent pathway can reduce the expression of p-Drp1(Ser616) and ameliorate hippocampal injury induced by global ischemia in rats. RESULTS: We found that pretreatment of the rats with Mdivi-1, a selective Drp1 inhibitor, decreased the level of transient global ischemia (TGI)-induced p-Drp1(Ser616) and reduced cellular contents of oxidized proteins, activated caspase-3 expression as well as the extent of DNA fragmentation...
2016: Journal of Biomedical Science
Hiroyo Ninomiya, Ayumu Hirata, Junji Kozawa, Shinsuke Nakata, Takekazu Kimura, Tetsuhiro Kitamura, Tetsuyuki Yasuda, Michio Otsuki, Akihisa Imagawa, Hideaki Kaneto, Tohru Funahashi, Iichiro Shimomura
The 3243 A>G mutation in mitochondrial DNA is the most common cause of monogenic diabetes mellitus in Japan. A 45-year-old woman with mitochondrial diabetes and significant insulin resistance presented with hypoadiponectinemia despite a normal amount of visceral fat. Three months of treatment with pioglitazone (PIO) improved her blood glucose profile and response to the 75-g oral glucose tolerance test. These changes were accompanied by the amelioration of her insulin resistance and the impairment of early-phase insulin secretion...
2016: Internal Medicine
Ibrahim Tugrul, Turhan Dost, Omer Demir, Filiz Gokalp, Ozlem Oz, Necip Girit, Mustafa Birincioglu
AIM: The aim of this study was to investigate the effects of pioglitazone and losartan pre-treatment on the aortic contractile response to the alpha-1 agonist, phenylephrine, and the alpha-2 agonist, clonidine, in L-NAME-induced hypertensive, STZ-induced diabetic, and hypertensive diabetic rats. METHODS: Male Wistar rats were randomly allocated to four groups: control, diabetic (DM), hypertensive (HT) and hypertensive diabetic (HT + DM) groups. Three weeks after drug application, in vitro dose-response curves to phenylephrine (Phe) (10(-9)-10(-5) M) and clonidine (Clo) (10(-9)-10(-5) M) were recorded in aortic rings in the absence (control) and presence of pioglitazone (10 µM) and/or losartan (10 µM)...
May 4, 2016: Cardiovascular Journal of Africa
Mei Liu, Adam D Bachstetter, Wayne A Cass, Jonathan Lifshitz, Guoying Bing
Increasing evidence suggests that traumatic brain injury (TBI) may raise the risk of developing late-onset Parkinson's disease (PD). Recently, the peroxisome proliferation-activated receptor gamma (PPARɣ) agonist pioglitazone has been demonstrated to be neuroprotective in animal models of neurodegeneration. The present study investigates the vulnerability of the nigrostriatal system after TBI, and intervention with pioglitazone treatment. Adult male Sprague-Dawley rats were subjected to sham or moderate midline fluid percussion brain injury, followed by an intraperitoneal injection of 10 mg/kg pioglitazone or vehicle beginning 30 min after the injury and subsequently every 24 h for 5 days...
May 3, 2016: Journal of Neurotrauma
Brahmchetna Bedi, Zhihong Yuan, Myungsoo Joo, Susu M Zughaier, Joanna B Goldberg, Jack L Arbiser, C Michael Hart, Ruxana T Sadikot
The pathogenic profile of Pseudomonas aeruginosa is related to its ability to secrete a variety of virulence factors. Quorum sensing (QS) is a mechanism wherein small diffusible molecules, specifically acyl-homoserine lactones, are produced by P. aeruginosa to promote virulence. We show here that macrophage clearance of P. aeruginosa (PAO1) is enhanced by activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ). Macrophages treated with a PPARγ agonist (pioglitazone) showed enhanced phagocytosis and bacterial killing of PAO1...
July 2016: Infection and Immunity
Daisuke Kamimura, Kazuaki Uchino, Tomoaki Ishigami, Michael E Hall, Satoshi Umemura
Left ventricular (LV) fibrosis plays an important role in the development of heart failure with preserved ejection fraction (HFpEF). We investigated whether chronic peroxisome proliferator-activated receptor gamma agonism with pioglitazone can prevent the development of HFpEF. We also evaluated the role of Wnt-β-catenin signaling in the development of HFpEF, and its relationship to peroxisome proliferator-activated receptor gamma signaling. Dahl salt-sensitive rats placed on an 8% NaCl diet from age 6 weeks were used as HFpEF model...
August 2016: Journal of Cardiovascular Pharmacology
S Shanmuga Priya, Ramalingam Sankaran, Sudha Ramalingam, Thiagarajan Sairam, L S Somasundaram
INTRODUCTION: Pro12Ala polymorphism is a missense mutation at codon 12 in peroxisome proliferator-activated receptor γ gene (PPARG). This polymorphism is known to be associated with increased insulin sensitivity. Pioglitazone, a thiazolidinedione, is an anti-diabetic drug which acts as an agonist at PPAR γ receptor. AIM: To determine the association between Pro12Ala polymorphism of the PPARG and variation in therapeutic response to the PPARγ agonist, pioglitazone...
February 2016: Journal of Clinical and Diagnostic Research: JCDR
Nina Prokoph, Mats Ormö, Gavin O'Mahony, Anders Hogner, Jane McPheat, Ulla Karlsson, Lovisa Holmberg Schiavone, Jianming Liu
The peroxisome proliferator-activated receptor gamma (PPARγ) is the target for the thiazolidinedione class of potent insulin-sensitizing drugs, which includes rosiglitazone and pioglitazone. However, their usage has been restricted due to severe side effects. Recent data have shown that specifically inhibiting the cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of PPARγ at Ser273 may lead to novel insulin sensitizers with fewer side effects. Here we describe a novel enzyme-linked immunosorbent assay (ELISA) in the 384-well format, which enables screening for PPARγ ligands that inhibit phosphorylation at Ser273 by Cdk5...
May 2016: Assay and Drug Development Technologies
Enas A Abd El-Haleim, Ashraf K Bahgat, Samira Saleh
Peroxisome proliferator-activated receptors (PPARs) gamma and alpha have been shown to play key roles in maintaining glucose and lipid homeostasis by acting as insulin sensitizers and lipid-lowering agents respectively, which would make them potential candidates for the treatment of non-alcoholic steatohepatitis (NASH) characterized by insulin resistance, hyperglycemia, and hypertriglyceridemia. The effects of pioglitazone, a PPAR-γ agonist, and fenofibrate, a PPAR-α agonist, as monotherapy and in combination on the expressions of key genes linked to the development of NASH were studied in rats with fructose-induced NASH...
February 15, 2016: European Journal of Pharmacology
Maximilian Pohland, Stephanie Hagl, Maren Pellowska, Mario Wurglics, Manfred Schubert-Zsilavecz, Gunter P Eckert
Developing new therapeutic strategies for Alzheimer's disease (AD) is a current challenge. Approved drugs merely act symptomatically and delay the progression of the disease for a relatively short period of time. Here, we investigated the effectiveness of MH84 in a cellular HEK293APPwt model of AD, characterized by elevated beta amyloid protein levels (Aβ1-42) and mitochondrial dysfunction. MH84 is a derivate of pirinixic acid belonging to a novel class of γ-secretase modulators, which combines γ-secretase modulation with activation of peroxisome proliferator-activator receptor gamma (PPARγ)...
February 2016: Neurochemical Research
Labanyamoy Kole, Mrinmoy Sarkar, Anwesha Deb, Biplab Giri
BACKGROUND: The thiazolidinedione (TZD) class of peroxisome proliferator-activated receptor gamma (PPAR-γ) ligands are known for their ability to induce adipocyte differentiation, to increase insulin sensitivity including anticancer properties. But, whether or not upstream events like MAPK activation or PPAR-γ signaling are involved or associated with this anticancer activity is not well understood in breast cancer cells. The role of MAPK and PPAR pathways during the pioglitazone (Pio) induced PPAR-γ independent anticancer activity in MCF7 cells has been focused here...
February 2016: Pharmacological Reports: PR
Raghavender Pottabathini, Anil Kumar, Archana Bhatnagar, Sukant Garg, E Ekavali
BACKGROUND: The relation between glutamate homeostasis and PPAR gamma has got tremendous importance in nerve trauma and pain. Present study has been designed to elucidate the interaction between the GLT-1 activator (ceftriaxone) and PPAR gamma agonist (pioglitazone) in the spinal nerve ligation induced neuropathic pain. METHODS: Male SD rats were subjected to spinal nerve ligation to induce neuropathic pain. Pioglitazone, ceftriaxone and their combination treatments were given for 28 days...
February 2016: Pharmacological Reports: PR
Jacqueline C Silva, Fernanda A César, Edson M de Oliveira, Walter M Turato, Gustavo L Tripodi, Gabriela Castilho, Adriana Machado-Lima, Beatriz de Las Heras, Lisardo Boscá, Marcelo M Rabello, Marcelo Z Hernandes, Marina G R Pitta, Ivan R Pitta, Marisa Passarelli, Martina Rudnicki, Dulcineia S P Abdalla
Peroxisome proliferator-activated receptor gamma (PPARγ) regulates multiple pathways involved in the pathogenesis of obesity and atherosclerosis. Here, we evaluated the therapeutic potential of GQ-177, a new thiazolidinedione, on diet-induced obesity and atherosclerosis. The intermolecular interaction between PPARγ and GQ-177 was examined by virtual docking and PPAR activation was determined by reporter gene assay identifying GQ-177 as a partial and selective PPARγ agonist. For the evaluation of biological activity of GQ-177, low-density lipoprotein receptor-deficient (LDLr(-/-)) C57/BL6 mice were fed either a high fat diabetogenic diet (diet-induced obesity), or a high fat atherogenic diet, and treated with vehicle, GQ-177 (20mg/kg/day), pioglitazone (20mg/kg/day, diet-induced obesity model) or rosiglitazone (15mg/kg/day, atherosclerosis model) for 28 days...
February 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
María José Pérez, Rodrigo A Quintanilla
Alzheimer's disease (AD) is a multifactorial metabolic brain disorder characterized by protein aggregates, synaptic failure, and cognitive impairment. In the AD brain is common to observe the accumulation of senile plaques formed by amyloid-beta (Aβ) peptide and the neurofibrillary tangles composed of modified tau protein, which both lead to cellular damage and progressive neurodegeneration. Currently, there is no effective therapy for AD; however several studies have shown that the treatments with the peroxisome proliferators activated receptor-gamma (PPARγ) agonists known as thiazolidinedione drugs (TZDs), like rosiglitazone and pioglitazone, attenuate neurodegeneration and improve cognition in mouse models and patients with mild-to-moderate AD...
2015: PPAR Research
Josephine M Egan
Combining a tyrosine kinase inhibitor (imatinib) and a thiazolidinedione (pioglitazone) is proposed for the treatment of chronic myeloid leukemia.
November 12, 2015: New England Journal of Medicine
Lekha Saha
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Three subtypes, PPARα, PPARβ/δ, and PPARγ, have been identified so far. PPARα is expressed in the liver, kidney, small intestine, heart, and muscle, where it activates the fatty acid catabolism and control lipoprotein assembly in response to long-chain unsaturated fatty acids, eicosanoids, and hypolipidemic drugs (e.g., fenofibrate). PPARβ/δ is more broadly expressed and is implicated in fatty acid oxidation, keratinocyte differentiation, wound healing, and macrophage response to very low density lipoprotein metabolism...
November 6, 2015: World Journal of Gastrointestinal Pharmacology and Therapeutics
Sanjay Kalra, Yashdeep Gupta
No abstract text is available yet for this article.
March 2015: JPMA. the Journal of the Pakistan Medical Association
Jia Liu, Lu-Ning Wang
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. OBJECTIVES: To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA)...
2015: Cochrane Database of Systematic Reviews
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