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Lactate AND Pioglitazone

M J Meneses, R L Bernardino, R Sá, J Silva, A Barros, M Sousa, B M Silva, P F Oliveira, M G Alves
Pioglitazone is a synthetic agonist for the nuclear receptor peroxisome proliferator-activated receptor γ used to treat type 2 diabetes mellitus. Recently we reported that antidiabetic drugs regulate the nutritional support of spermatogenesis by Sertoli cells. Herein, we investigate the effects of pioglitazone on human Sertoli cells metabolism. Human Sertoli cells were cultured in the presence of pioglitazone (1, 10, 100μM). Protein levels of phosphofructokinase 1, lactate dehydrogenase, hexokinase, glucose transporters (GLUT1, GLUT2, GLUT3), monocarboxylate transporter 4 and oxidative phosphorylation complexes were determined by Western blot...
October 2016: International Journal of Biochemistry & Cell Biology
Dhiraj Mittal, Rajeev Taliyan, P L Sharma, Harlokesh Narayan Yadav
OBJECTIVES: The signaling pathways upstream of glycogen synthase kinase-3β (GSK-3β) get reduced during ischemic preconditioning (IPC) in hyperlipidemic rat heart. Pioglitazone, an insulin sensitizer, exerts cardioprotection through GSK-3β. The objective of the study is to investigate the role of pioglitazone on the attenuated cardioprotective effect of IPC in hyperlipidemic rat heart. MATERIALS AND METHODS: The rats were administered high-fat diet for 8 weeks to induce experimental hyperlipidemia (HL)...
January 2016: Indian Journal of Pharmacology
Weiran Ye, Yijia Zheng, Shanshan Zhang, Li Yan, Hua Cheng, Muchao Wu
Oxamate (OXA) is a pyruvate analogue that directly inhibits the lactate dehydrogenase (LDH)-catalyzed conversion process of pyruvate into lactate. Earlier and recent studies have shown elevated blood lactate levels among insulin-resistant and type 2 diabetes subjects and that blood lactate levels independently predicted the development of incident diabetes. To explore the potential of OXA in the treatment of diabetes, db/db mice were treated with OXA in vivo. Treatment of OXA (350-750 mg/kg of body weight) for 12 weeks was shown to decrease body weight gain and blood glucose and HbA1c levels and improve insulin secretion, the morphology of pancreatic islets, and insulin sensitivity in db/db mice...
2016: PloS One
Ali Reza Yousefi, Hamid Kohram, Ahmad Zare Shahneh, Mohammad Javad Zamiri, Ali Akbar Fouladi-Nashta
The objective of this study was to investigate the effect of dietary supplementation of pioglitazone (PGT), a specific ligand for PPARγ, on metabolic dynamics, milk production, and reproductive performance of transition dairy cows. Eighty multiparous Holstein cows in their second or more lactations were blocked by the calving date and parity and assigned randomly to four dietary groups (n = 20 cow/treatment) including control (no PGT-/-), supplemented with PGT (6-mg PGT/kg body weight) from Day -14 to +21 relative to parturition (PGT+/+) or only during prepartum (PGT+/-) or postpartum periods (PGT-/+)...
June 2016: Theriogenology
Uma Bhandari, Vinay Kumar, Parveen Kumar, C D Tripathi, Geetika Khanna
BACKGROUND & OBJECTIVES: Cardiomyocyte apoptosis is one of the pathologic phenomena associated with diabetes and related conditions including obesity, insulin resistance and hyperlipidaemia. In the present study, the protective effects of pioglitazone on cardiomyocyte apoptosis was evaluated in experimental diabetes induced by low dose of streptozoticin (STZ) combined with high fat diet (HFD) in rats. METHODS: Male Wistar rats (150-200 g) were injected with low-dose STZ (45 mg/kg, i...
November 2015: Indian Journal of Medical Research
Noha M Shawky, George S G Shehatou, Mona Abdel Rahim, Ghada M Suddek, Nariman M Gameil
This study investigates the possible protective effects of levocetirizine against fructose-induced insulin resistance, hepatic steatosis and vascular dysfunction, in comparison to pioglitazone, a standard insulin sensitizer. Male Sprague Dawley rats (150-200 g) were divided into 4 groups. Three groups were fed on high fructose diets (HFD) containing 60% w/w fructose, while the fourth control group was fed on standard laboratory food for 8 weeks. AUCOGTT, AUCITT, fasting glucose, HOMA-IR, hepatic glutathione (GSH) and malondialdehyde (MDA) levels, serum total cholesterol, LDL-C, C-reactive protein (CRP) level and lactate dehydrogenase (LDH) activity and liver steatosis scores were significantly higher in HFD group compared to control group...
October 5, 2014: European Journal of Pharmacology
Azza A K El-Sheikh, Rehab A Rifaai
Hepatoprotective potential of peroxisome proliferator activator receptor (PPAR)- α and - γ agonists, fenofibrate (FEN), and pioglitazone (PIO), respectively, against cyclophosphamide (CP)-induced toxicity has been investigated in rat. FEN and PIO (150 and 10 mg/kg/day, resp.) were given orally for 4 weeks. In separate groups, CP (150 mg/kg, i.p.) was injected as a single dose 5 days before the end of experiment, with or without either PPAR agonist. CP induced hepatotoxicity, as it caused histopathological alterations, with increased serum alanine and aspartate transaminases, total bilirubin, albumin, alkaline phosphatase and lactate dehydrogenase...
2014: PPAR Research
Krishna Mohan Surapaneni, Mallika Jainu
BACKGROUND: Non alcoholic steatohepatitis (NASH), severe form of diseases belonging to the spectrum of the Non alcoholic fatty liver disease (NAFLD). It is an asymptomatic disease which leads to fibrosis and finally to cirrhosis, an end stage liver disease. OBJECTIVE: To study the effect of pioglitazone, quercetin and hydroxy citric acid on hepatic biomarkers and various biochemical parameters in experimentally induced non alcoholic steatohepatitis (NASH). MATERIALS AND METHODS: Male Wister rats were divided into 8 groups...
April 2014: Pharmacognosy Research
Timothy D Whitehead, Samuel T Nemanich, Carmen Dence, Kooresh I Shoghi
UNLABELLED: Research and discovery of novel radiopharmaceuticals and targets thereof generally involves initial studies in cell cultures, followed by animal studies, both of which present several inherent limitations. The objective of this work was to develop a tissue bioreactor (TBR) enabling modulation of the microenvironment and to integrate the TBR with a small-animal PET scanner to facilitate imaging biomarker research and discovery and validation of radiopharmaceuticals. METHODS: The TBR chamber is a custom-blown, water-jacketed, glass vessel enclosed in a circulating perfusion bath powered by a peristaltic pump, which is integrated within the field of view of the PET scanner...
October 2013: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Sania Grover, Puneet Kumar, Kuldeep Singh, Vir Vikram, R D Budhiraja
Tardive dyskinesia is a type of hyperkinetic movement disorder which consists of abnormal involuntary movements, characterized by orofacial movements. Previous studies suggest that oxidative stress and neuro-inflammation play important role in the pathogenesis of TD. Recently, PPAR-α and PPAR-ϒ have been reported as neuroprotective agent in various animal models. The present study investigated the neuroprotective effect of PPAR-ϒ agonist, pioglitazone (20 and 40 mg/kg, p.o.) and PPAR-α agonist, fenofibrate (100 and 200mg/kg, p...
October 2013: Pharmacology, Biochemistry, and Behavior
Arshag Kalanderian, Nicola Abate, Igor Patrikeev, Jingna Wei, Kathleen Listiak Vincent, Massoud Motamedi, George Robert Saade, Egle Bytautiene
OBJECTIVE: Pioglitazone (PIO), an antidiabetic drug of the thiazolidinedione family, improves glucose and lipid metabolism in muscle, adipose, and liver tissues via peroxisome proliferator-activated receptor gamma activation. We hypothesize that PIO therapy will improve the metabolic status of offspring exposed to maternal obesity in a mouse model developmentally programmed for metabolic syndrome. STUDY DESIGN: CD-1 female mice were fed a high-fat diet for 3 months prior to breeding and throughout pregnancy and lactation...
April 2013: American Journal of Obstetrics and Gynecology
F Masciopinto, N Di Pietro, C Corona, M Bomba, C Pipino, M Curcio, A Di Castelnuovo, D Ciavardelli, E Silvestri, L M T Canzoniero, I Sekler, A Pandolfi, S L Sensi
In this study, we investigated the effects of long-term (9-month) treatment with pioglitazone (PIO; 20 mg/kg/d) in two animal models of Alzheimer's disease (AD)-related neural dysfunction and pathology: the PS1-KI(M146V) (human presenilin-1 (M146V) knock-in mouse) and 3xTg-AD (triple transgenic mouse carrying AD-linked mutations) mice. We also investigated the effects on wild-type (WT) mice. Mice were monitored for body mass changes, fasting glycemia, glucose tolerance, and studied for changes in brain mitochondrial enzyme activity (complexes I and IV) as well as energy metabolism (lactate dehydrogenase (LDH))...
2012: Cell Death & Disease
Arghya Biswas, Syed Imam Rabbani, Kshama Devi
OBJECTIVES: To investigate the effect of pioglitazone on isoproterenol-induced heart failure and high-fructose diet-induced metabolic changes in rats. MATERIALS AND METHODS: Three doses of pioglitazone (Pio - 3, 10, 30 mg/kg, po) were tested in male Wistar rats. In the Heart Failure (HF) group, treatment was followed by Isoproterenol (ISO) injection. The markers for HF, such as enzyme estimation, relative heart weight, and antioxidant status, were evaluated. In another group, metabolic disturbances were induced by High Fructose Diet (HFD)...
May 2012: Indian Journal of Pharmacology
Tao Chen, Xiaoping Jin, Brian H Crawford, Hua Cheng, Talib B Saafir, Mary B Wagner, Zuyi Yuan, Guoliang Ding
Regulation of catalase (CAT) by peroxisome proliferator-activated receptor-γ (PPARγ) was investigated to determine if PPARγ activation provides cardioprotection from oxidative stress caused by hydrogen peroxide (H(2)O(2)) in an age-dependent manner. Left ventricular developed pressure (LVDP) was measured in Langendorff perfused newborn or adult rabbit hearts, exposed to 200μM H(2)O(2), with perfusion of rosiglitazone (RGZ) or pioglitazone (PGZ), PPARγ agonists. We found: (1) H(2)O(2) significantly decreased sarcomere shortening in newborn ventricular cells but not in adult cells...
July 15, 2012: Free Radical Biology & Medicine
Lamiaa A Ahmed, Hesham A Salem, Amina S Attia, Azza M Agha
The present investigation was designed to study the cardioprotective effects of nicorandil and pioglitazone preconditioning in myocardial ischemia/reperfusion-induced hemodynamic, biochemical and histological changes in rats. Oral doses of nicorandil (3 or 6 mg/kg) and pioglitazone (10 or 20mg/kg) were administered once daily for 5 consecutive days. Rats were then subjected to myocardial ischemia/reperfusion (40 min/10 min). Heart rate and ventricular arrhythmias were recorded during ischemia/reperfusion progress...
August 1, 2011: European Journal of Pharmacology
Guy L Weinberg, Richard Ripper, Sarah Bern, Bocheng Lin, Lucas Edelman, Guido Digregorio, Mariann Piano, Douglas L Feinstein
BACKGROUND: The authors tested whether cocaine depresses mitochondrial acylcarnitine exchange and if a drug that enhances glucose metabolism could protect against cocaine-induced cardiac dysfunction. METHODS: Oxygen consumption with and without cocaine was compared in rat cardiac mitochondria using octanoylcarnitine (lipid) or pyruvate (nonlipid) substrates. Isolated hearts from rats with or without a pioglitazone-supplemented diet were exposed to cocaine. RESULTS: The 0...
June 2011: Anesthesiology
Barbara Brunmair, Katrin Staniek, Zsuzsanna Lehner, Debendranath Dey, Charles W Bolten, Karin Stadlbauer, Anton Luger, Clemens Fürnsinn
The pharmacology of thiazolidinediones (TZDs) seems to be driven not only by activation of peroxisome proliferator-activated receptor-γ (PPARγ), but also by PPARγ-independent effects on mitochondrial function and cellular fuel handling. This study portrayed such actions of the novel hydrophilic TZD compound BLX-1002 and compared them to those of conventional TZDs. Mitochondrial function and fuel handling were examined in disrupted rat muscle mitochondria, intact rat liver mitochondria, and specimens of rat skeletal muscle...
June 2011: American Journal of Physiology. Cell Physiology
H-L Zhang, M Xu, C Wei, A-P Qin, C-F Liu, L-Z Hong, X-Y Zhao, J Liu, Z-H Qin
Previous studies have demonstrated that pioglitazone (Piog), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, inhibits ischemia-induced brain injury. Piog has also been shown to exert anti-inflammatory effects by attenuation of nuclear factor-κB (NF-κB) activation after myocardial ischemia/reperfusion injury. Because NF-κB is known to play a major role in the pathophysiology of brain ischemia, the present study was undertaken to elucidate whether pioglitazone attenuates ischemic neuronal damage through PPARγ-mediated suppression of NF-κB apoptotic signaling pathway...
March 10, 2011: Neuroscience
Lourdes Ibáñez, Abel López-Bermejo, Marta Díaz, Goya Enríquez, Luis Del Río, Francis De Zegher
CONTEXT: Therapy of androgen excess should not only confer cosmetic benefit, but also improve long-term markers of endocrine-metabolic and cardiovascular health. Here we report on our pilot experience with a low-dose polytherapy for 30 months. DESIGN, PATIENTS, INTERVENTION: Unblinded extension (24-30 months) of a double-placebo study exploring low-dose polytherapy over 24 months. Between 24 and 30 months, women with hyperinsulinemic androgen excess (N = 36; mean age: 19.4 year; BMI: 23...
December 2010: Gynecological Endocrinology
Eva Gottfried, Sebastian Rogenhofer, Heidi Waibel, Leoni A Kunz-Schughart, Albrecht Reichle, Monika Wehrstein, Alice Peuker, Katrin Peter, Gabi Hartmannsgruber, Reinhard Andreesen, Marina Kreutz
The anti-diabetic thiazolidinedione compound pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, and selective cyclooxygenase-2 inhibitors are clinically used in patients with advanced malignancies. Several previously published in vivo and in vitro studies showed growth inhibitory effects on different cancer cell lines. However, the underlying mechanisms are fairly unclear. Here, we analyzed the effects of pioglitazone in combination with other drugs in a three-dimensional multicellular tumor spheroid culture system (MCTS) generated from the two prostate carcinoma cell lines PC3 and LNCaP...
January 2011: Cancer Chemotherapy and Pharmacology
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