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Pioglitazone AND kidney

Said Said Elshama, Ayman El-Meghawry El-Kenawy, Hosam-Eldin Hussein Osman
OBJECTIVES: Pioglitazone (Actos) is one of the most controversial recent oral antidiabetic drugs. It was originally authorized in the European Union in 2000, and approved as an oral monotherapy for overweight second type of diabetic patients in 2002. It belongs to the thiazolidinedione group which some of its members have been withdrawn from the market due to the hepatotoxicity or cardiotoxicity effects. This study investigates sub-chronic use of pioglitazone induced toxicity in mice by the assessment of renal and liver function tests, cardiac enzymes, and some hematological indices with histological changes of liver, kidney, heart, and bladder...
July 2016: Iranian Journal of Basic Medical Sciences
Rowaida Refaat, Ahmed Sakr, Mona Salama, Ashgan El Sarha
Preclinical Research The majority of studies on vildagliptin and pioglitazone have focused on their combination in glycemic control. The aim of the present study was to investigate their effects in combination on (i) hyperglycemia-induced oxidative stress and inflammation and (ii) on organs involved in the pathophysiology of diabetes, pancreas, kidney and liver. Type 2 diabetes was induced using low-dose streptozotocin in male Wistar rats. Diabetic rats were treated for 4 weeks, with vildagliptin (10 mg/kg/day), pioglitazone (10 mg/kg/day) and their combination...
September 2016: Drug Development Research
Melanie Davies, Sudesna Chatterjee, Kamlesh Khunti
Worldwide, an estimated 200 million people have chronic kidney disease (CKD), the most common causes of which include hypertension, arteriosclerosis, and diabetes. Importantly, ~40% of patients with diabetes develop CKD, yet evidence from major multicenter randomized controlled trials shows that intensive blood glucose control through pharmacological intervention can reduce the incidence and progression of CKD. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin...
2016: Clinical Pharmacology: Advances and Applications
Amrit Pal Singh, Nirmal Singh, Preet Mohinder Singh Bedi
The present study investigated the role of N-methyl-D-aspartate (NMDA) receptors in pioglitazone-mediated protection against renal ischemia reperfusion injury (IRI) in rats. Male wistar rats were subjected to 40 min of bilateral renal ischemia followed by reperfusion for 24 h to induce kidney injury. The renal damage was evaluated by measuring serum creatinine, creatinine clearance, blood urea nitrogen, uric acid, electrolytes, and microproteinuria in rats. Oxidative stress in renal tissues was quantified in terms of myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione level...
June 2016: Molecular and Cellular Biochemistry
Swetha Chandru, Prashant Vishwanath, Devananda Devegowda, Suresha Nagaraja Ramasamudra, Akila Prashant, Basavanagowdappa Hathur
INTRODUCTION: The present study was taken up to compare and evaluate the effect of Momordica charantia supplementation with pioglitazone on PKC-β and PPAR-γ activity in kidneys of diabetic rats. The hypoglycaemic and lipid lowering effect of Momordica charantia were screened in laboratory animal model and its potency was compared with a Thiazolidinedione (TZD) group antidiabetic drug like pioglitazone. MATERIALS AND METHODS: Adult healthy albino rats of Wistar strain aged 3-4months, weighing between 170-250gm of either sex were divided into 4 groups; Group 1 (normal controls), Group 2 (diabetic controls), Group 3 (diabetic rats treated with pioglitazone) and Group 4 (diabetic rats treated with bitter melon juice)...
April 2016: Journal of Clinical and Diagnostic Research: JCDR
Li Sun, Quan Yuan, Tianhua Xu, Li Yao, Jiangmin Feng, Jianfei Ma, Lining Wang, Changlong Lu, Danan Wang
BACKGROUND/AIMS: Pioglitazone is a type of peroxisome proliferator-activated receptor x03B3; agonist and is capable of alleviating renal ischemia-reperfusion injury. METHODS: A5/6 nephrectomized rat model was established to induce renal impairments mimicking chronic kidney diseases (CKDs). The effect of pioglitazone on renal structure, function, antioxidative capacity, and angiogenesis in the nephrectomized rats was assessed. Moreover, the expression of HIF-1α, eNOS, VEGF, Flt-1 and Flk-1 was determined to reveal the possible pathways through which pioglitazone exerted its beneficial effect on CKDs...
2016: Cellular Physiology and Biochemistry
Yao-Wu Liu, Xia Zhu, Ya-Qin Cheng, Qian Lu, Fan Zhang, Hao Guo, Xiao-Xing Yin
Ibuprofen, a commonly administered nonsteroidal anti‑inflammatory therapeutic agent, is also a partial agonist of peroxisome proliferator‑activated receptor γ (PPARγ). The present study investigated the effects of ibuprofen on type 1 diabetic nephropathy (DN) in rats, and the potential mechanisms associated with the activation of PPARγ. Diabetic rats were induced through a single intraperitoneal injection of streptozotocin before oral treatment with ibuprofen or pioglitazone for 8 weeks. The 24‑h urine collection was performed for measurement of total protein content...
June 2016: Molecular Medicine Reports
Samia M Ali, Hoda Khalifa, Dalia K Mostafa, Amal El Sharkawy
AIM: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease, and thus, the ability of antidiabetic drugs to ameliorate renal microvascular disease may be as important as their ability to control blood glucose. Therefore, we investigated the reno-protective effect of the antidiabetic drugs, Sitagliptin and Pioglitazone, versus combined Metformin/Enalapril in a rat model of type 2 diabetes. METHOD: Male Wistar rats were randomly assigned to be either normal control or diabetic...
May 15, 2016: Life Sciences
Piero Vasapollo, Erika Cione, Filippo Luciani, Luca Gallelli
Selective agents able to locate and identify unique targets represent a crucial aspect of modern pharmacology. The exclusive location of sodium-glucose co-transporter-2 (SGLUT2) on kidneys prompt companies to develop SGLT2 inhibitors that today are the latest class of drugs for diabetes treatment. In particular, canagliflozin blocks the re-absorption of glucose in the kidney lowering blood glucose levels by increasing glucose excretion. We report a 61-year old woman who developed an intense and severe pruritus during the treatment with canagliflozin...
April 5, 2016: Current Drug Safety
Kazumi Taguchi, Atsushi Okada, Shuzo Hamamoto, Rei Unno, Takahiro Kobayashi, Ryosuke Ando, Keiichi Tozawa, Bing Gao, Kenjiro Kohri, Takahiro Yasui
Peroxisome proliferator-activated receptors (PPARs) and related inflammatory and oxidative molecule expression were investigated in a hyperoxaluric rodent model to evaluate the in vivo efficacy of PPAR agonists in preventing renal crystal formation. PPAR expression was examined in a mouse hyperoxaluria kidney stone model induced by daily intra-abdominal glyoxylate injection. Therapeutic effects of the PPARα agonist fenofibrate and PPARγ agonist pioglitazone were also assessed in a 1% ethylene glycol-induced rat model of hyperoxaluria...
2016: PPAR Research
Keizo Matsushita, Hai-Chun Yang, Manu M Mysore, Jianyong Zhong, Yu Shyr, Li-Jun Ma, Agnes B Fogo
We previously observed that high-dose angiotensin receptor blocker (ARB) can induce regression of existing glomerulosclerosis. We also found that proliferator-activated recepto-γ (PPARγ) agonist can attenuate glomerulosclerosis in a nondiabetic model of kidney disease, with specific protection of podocytes. We now assessed effects of combination therapy with ARB and pioglitazone on established glomerulosclerosis. Sprague-Dawley male rats underwent 5/6 nephrectomy (5/6 Nx) at week 0 and renal biopsy at week 8...
June 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
K K Clemens, K Liu, S Shariff, G Schernthaner, N Tangri, A X Garg
AIM: To examine how antihyperglycaemic medications were prescribed to older adults with diabetes and chronic kidney disease over the last decade. METHODS: We conducted a population-based study of 144 252 older adults with diabetes and chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73 m(2) or receiving chronic dialysis) in Ontario, Canada. In each study quarter (3-month intervals from 1 April 2004 until 31 March 2013) we studied the proportion of treated and newly treated patients prescribed insulin, sulphonylureas, α-glucosidase inhibitors, metformin, thiazolidinediones, meglitinides and dipeptidyl peptidase-4 (DPP-4) inhibitors...
June 2016: Diabetes, Obesity & Metabolism
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
Mai M Helmy, Maged W Helmy, Mahmoud M El-Mas
Nephrotoxicity is a major side effect for the antineoplastic drug cisplatin. Here, we employed pharmacological, biochemical, and molecular studies to investigate the role of peroxisome proliferator-activated receptors (PPARs) in cisplatin nephrotoxicity. Rats were treated with a single i.p. dose of cisplatin (5 mg/kg) alone or combined with pioglitazone (PPARγ agonist), fenofibrate (PPARα agonist), pioglitazone plus fenofibrate, or thalidomide (Tumor necrosis factor-α inhibitor; TNF-α). Cisplatin nephrotoxicity was evidenced by rises in renal indices of functional (blood urea nitrogen, BUN, and creatinine), inflammatory (TNF-α, interleukin 6, IL-6), oxidative (increased malondialdehyde, MDA, and decreased superoxide dismutase, SOD and nitric oxide metabolites, NOx), apoptotic (caspase 3), and histological (glomerular atrophy, acute tubular necrosis and vacuolation) profiles...
2015: PloS One
Gurkishan S Chadha, Marilyn E Morris
Although many studies have evaluated the effects of type 2 diabetes mellitus (T2DM) on the pharmacokinetics (PK) of low molecular weight molecules, there is limited information regarding effects on monoclonal antibodies. Our previous studies have reported significant increases in total (2-4 fold) and renal (100-300 fold) clearance of human IgG, an antibody isotype, in Zucker diabetic fatty (ZDF) rats. Pioglitazone treatment incompletely reversed the disease-related PK changes. The objective of this study was to construct a mechanistic model for simultaneous fitting plasma and urine data, to yield physiologically relevant PK parameters...
November 2015: AAPS Journal
Juan-E Li, Kumi Futawaka, Hiroyuki Yamamoto, Masato Kasahara, Tetsuya Tagami, Tong-Hua Liu, Kenji Moriyama
Cinnamon is a traditional folk herb used in Asia and has been reported to have antidiabetic effects. Our previous study showed that cinnamaldehyde (CA), a major effective compound in cinnamon, exhibited hypoglycemic and hypolipidemic effects together in db/db mice. The aim of the present study was to elucidate the molecular mechanisms of the effects of CA on the transcriptional activities of three peroxisome proliferator-activated receptors, (PPAR) α, δ, and γ. We studied the effects of CA through a transient expression assay with TSA201 cells, derivatives of human embryonic kidney cell line (HEK293)...
2015: American Journal of Chinese Medicine
James D Lewis, Laurel A Habel, Charles P Quesenberry, Brian L Strom, Tiffany Peng, Monique M Hedderson, Samantha F Ehrlich, Ronac Mamtani, Warren Bilker, David J Vaughn, Lisa Nessel, Stephen K Van Den Eeden, Assiamira Ferrara
IMPORTANCE: Studies suggest pioglitazone use may increase risk of cancers. OBJECTIVE: To examine whether pioglitazone use for diabetes is associated with risk of bladder and 10 additional cancers. DESIGN, SETTING, AND PARTICIPANTS: Cohort and nested case-control analyses among persons with diabetes. A bladder cancer cohort followed 193,099 persons aged 40 years or older in 1997-2002 until December 2012; 464 case patients and 464 matched controls were surveyed about additional confounders...
July 21, 2015: JAMA: the Journal of the American Medical Association
Suguru Yamamoto, Jiayong Zhong, Patricia G Yancey, Yiqin Zuo, MacRae F Linton, Sergio Fazio, Haichun Yang, Ichiei Narita, Valentina Kon
OBJECTIVE: Chronic kidney disease (CKD) amplifies atherosclerosis, which involves renin-angiotensin system (RAS) regulation of macrophages. RAS influences peroxisome proliferator-activated receptor-γ (PPARγ), a modulator of atherogenic functions of macrophages, however, little is known about its effects in CKD. We examined the impact of combined therapy with a PPARγ agonist and angiotensin receptor blocker on atherogenesis in a murine uninephrectomy model. METHODS: Apolipoprotein E knockout mice underwent uninephrectomy (UNx) and treatment with pioglitazone (UNx + Pio), losartan (UNx + Los), or both (UNx + Pio/Los) for 10 weeks...
September 2015: Atherosclerosis
Sahar M El-Gowilly, Mai M Helmy, Hanan M El-Gowelli
Methotrexate (MTX) is widely used in treatment of cancers and autoimmune diseases. However, nephrotoxicity is one of its most important side effects. The peroxisome proliferator-activated receptor gamma agonist, pioglitazone, is known to exert antiinflammatory and reno-protective effects in various kidney injuries. The purpose of this study was to investigate the potential involvement of endothelial damage in MTX-induced renal injury and to elaborate the possible protective effect of pioglitazone against MTX-induced endothelial impairment...
November 2015: Vascular Pharmacology
Nicoletta Charolidi, Grisha Pirianov, Evelyn Torsney, Stuart Pearce, Ken Laing, Axel Nohturfft, Gillian W Cockerill
Peroxisome proliferator-activated receptor x03B3; agonists have been shown to inhibit angiotensin II (AngII)-induced experimental abdominal aortic aneurysms. Macrophage infiltration to the vascular wall is an early event in this pathology, and therefore we explored the effects of the peroxisome proliferator-activated receptor x03B3; agonist pioglitazone on AngII-treated macrophages. Using microarray-based expression profiling of phorbol ester-stimulated THP-1 cells, we found that a number of aneurysm-related gene changes effected by AngII were modulated following the addition of pioglitazone...
2015: Journal of Vascular Research
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