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Effects of Pioglitazone, Glimepiride, Nobivolol, Valsartan and Hesperidine on Serum Diabetic Marker and Lipid Metabolizing Enzymes in Isoproterenol Induced Myocardial Infarction in Normal and Diabetic Rats
Jagdish Kakadiya, Nehal Shah
International Journal of Research in Pharmaceutical Sciences , 2010,
Abstract: Present study was designed to evaluate effect some synthetic drugs and some herbal compound on Glucose, HbA1c and Lipid Metabolizing Enzymes in isoproterenol induced myocardial infarction in normal and Streptozotocin-Nicotinamide induced diabetic in rats. Pioglitazone (10 mg/kg, p.o), Glimepiride (0.5 mg/kg, p.o), Nobivolol (2 mg/kg, p.o), Valsartan (8 mg/kg, p.o) and Hesperidin (100 mg/kg, p.o) were administered for 28 days in rats injected with single dose of Streptozotocin (65 mg/kg, i.p, STZ) and Nicotinamide (12mg/kg, i.p, NIC) and after isoproterenol (200 mg/kg, s.c.) induced myocardial infarction in rats on 29th and 30th day. At the end of experimental period (i.e. on the day 31) serum and heart tissues sample were collected, and glucose, HbA1c and cholesterol ester synthetase (CES), lecithin Cholesterol acyl transferase (LCAT), lipoprotein lipase (LPL) were find out. Administration of STZ–NIC in rats showed a significant (p<0.001) increased in the levels of serum glucose, glycosylated hemoglobin (HbA1c), significant (p<0.001) increased in the level of heart tissues CES and significant (p<0.001, p<0.01) decreased LCAT and LPL as compared to respective control groups. Treatment with Pioglitazone, Glimepiride significantly (P<0.001) decreased and Hesperidin significant (P<0.05) decreased HbA1c, glucose and CES level but treatment with nobivolol significant (p<0.05) decreased CES level without change on glucose and HbA1c. Treatment with Pioglitazone and Glimepiride significantly (P<0.001) increased and Hesperidin and Nobivolol (P<0.01) increased LCAT and LPL as compared to diabetic control. Treatment with Valsartan shows no change on Glucose, HbA1c and lipid metabolizing enzyme in diabetic rats. This study concluded that Pioglitazone and Glimepiride may show reduced diabetes marker, CES and protect LCAT and LPL on experimentally induced myocardial infarction in type 2 diabetic rats.
The Effect of Pioglitazone on Antioxidant Levels and Renal Histopathology in Streptozotocin-Induced Diabetic Rats  [PDF]
Munire Kuru Karabas,Mediha Ayhan,Engin Guney,Mukadder Serter,Ibrahim Meteoglu
ISRN Endocrinology , 2013, DOI: 10.1155/2013/858690
Abstract: Objective. Diabetic nephropathy is the most commonly seen cause of chronic renal failure, and oxidative stress is important in etiology. In the present study, favorable effects (if any) of the treatment with a thiazolidinedione group drug, pioglitazone, on antioxidant enzyme levels in the renal tissue, renal histopathology, and inflammatory cytokine levels have been investigated. Method. Forty male Wistar rats were divided into 4 groups as the control, diabetic control, and 10 and 30?mg pioglitazone-administered diabetic groups. After 4 weeks, antioxidant enzyme levels in renal tissues and inflammatory markers were investigated. Results. Blood glucose levels did not differ between the diabetic control and drug-administered groups. In pioglitazone-administered rats, histopathological findings such as tubular dilation, necrotic tubular epithelium, glomerular focal necrosis, and vascular consolidation were observed at a lesser extent than the diabetic control group. Any difference was not detected between the diabetic groups with respect to the levels of malondialdehyde, superoxide dismutase, catalase, glutathione, nitric oxide, interleukin-6, and tumor necrosis factor-alpha. Conclusion. Pioglitazone regressed development of histopathological lesions such as glomerular focal necrosis, tubular epithelial necrosis, tubular dilation, and vascular wall consolidation. However, any favorable effect on antioxidant enzyme levels in renal tissues and inflammation markers was not detected. 1. Introduction Diabetes mellitus has become the most frequently seen global etiological factor for the end-stage renal failure. According to the data published by World Health Organization, in the year 2030, the number of diabetics was predicted to amount to 370 million patients [1]. As proved in many investigations, strict glycemic and heart rate control prevent occurrence and progression of diabetic nephropathy [2–4]. However, especially in some of the type 2 DM patients, complications already develop at the time of diagnosis, and strict glycemic control cannot be always achieved. Therefore, development of treatment modalities preventing occurrence or progression of diabetic nephropathy seems to be an urgent need. Pathophysiological mechanisms contributing to the formation of diabetic nephropathy and treatment modalities directing to that end have been investigated. Increased activation of polyol, protein kinase c and hexosamine pathways, and intracellular AGEs (advanced glycation end products) were determined as basic mechanisms of hyperglycemic tissue damage [5]. Oxidative
Pioglitazone induced weight changes in type 2 diabetic patients  [cached]
Sayantani Ghosh,Saugat Dey
International Journal of Collaborative Research on Internal Medicine & Public Health , 2011,
Abstract: Background: Pioglitazone, a member of the thiazolidinedione drug family, with hypoglycemic action, is widely used for the therapy of type 2 diabetic patients.Aims and Objectives: The effect of pioglitazone on body weight was investigated and the effects of monotherapy and combinations with other hypoglycemic agents were compared.Methodology: A prospective study on 379 type 2 diabetic cases, who were being given pioglitazone for the first time, as either monotherapy or in combination with other oral hypoglycemic agents or insulin. Parameters were analyzed by Kruskal-Wallis test, considering p <0.05 as significant.Results: Pioglitazone therapy resulted in weight gain, especially in females, although triglyceride and lipoprotein levels were not adversely affected. Concomitant use of pioglitazone along with insulin or any of the sulfonylurea group of drugs accounted for more weight gain; (2.57±1.4 kg) and (2.31±1.2 kg) respectively; than that by pioglitazone alone (2.23±1.3 kg). However pioglitazone combination therapy with metformin and alpha glycosidase inhibitors revealed lower weight gain: (0.31±0.2 kg) and (0.16±0.4 kg) respectively. Higher doses of pioglitazone were associated with more important weight gain.Limitations of the study:1. The study is an open-label prospective observational study and not a double blinded randomized controlled trial.2. Long term changes in weight were not assessed, as the mean follow up period was only 6 months.3. There were very few patients (only 28) on pioglitazone monotherapy. Conclusions: Pioglitazone increases body weight, although less than other thiazolidinediones. Hence it should not be indiscriminately used in high doses and when used, it should be supplemented with metformin and alpha glycosidase inhibitors.
Glipizide Pharmacokinetics in Healthy and Diabetic Volunteers
M Atif, M Ahmad, M Qamar-uz-zaman, M Asif, SAS Sulaiman, AA Shafie, I Masood, U Minhas, N Us-saqib
Tropical Journal of Pharmaceutical Research , 2011,
Abstract: Purpose: Disease state may contribute to alteration in drug pharmacokinetics. The purpose of this study was to determine the effect of non-insulin dependent diabetes mellitus (NIDDM) on the pharmacokinetics of glipizide. Methods: An open, single-dose, parallel design was applied to the study. Glipizide tablet (5 mg) was administered to healthy and diabetic human volunteers after over-night fast. Blood samples were collected, centrifuged and the plasma assayed using a sensitive and validated reverse phase high performance liquid chromatography (RP-HPLC) method. Various pharmacokinetic parameters were computed from the data obtained. Results: The AUC0- values for healthy and diabetic volunteers was 1878 ± 195 and 1723 ± 138 ng.h/ml, respectively; these values were not significantly different (p > 0.05). The t1/2 for healthy volunteers was 3.04 ± 0.27 h while that for diabetic subjects was 2.98 ± 0.16 h. Clearance for healthy and diabetic volunteers was 0.59±0.06 and 0.64±0.05 ml/min/kg, respectively. These and other pharmacokinetic parameters assessed were not significantly different between healthy and diabetic volunteers (p > 0.05). Conclusion: Although glipizide showed slightly more rapid clearance from the body of diabetic volunteers than from healthy volunteers, this difference, like those for other pharmacokinetic parameters, was not significant (p > 0.05).
Comparison of the Hypoglycemic, Hypolipidemic and Hepatoprotective Effects of Asparagus racemosus Linn. in Combination with Gliclazide and Pioglitazone on Alloxan-Induced Diabetic Rats  [PDF]
Abdullah Al Mamun, Mahbubul Hossain, Md. Sahab Uddin, Md. Tanjir Islam, Sajjad Hossain, Md. Sarwar Hossain, Md. Farhad Hossain, Ataur Rahman Sujan, Mamunur Rashid, Md. Mahbubur Rahman, A. F. M. Towheedur Rahman
Pharmacology & Pharmacy (PP) , 2017, DOI: 10.4236/pp.2017.82004
Abstract: In recent years, the popularity of medicinal plants as a remedy has been increased manifold due to having minimal adverse effects. The current study aimed to compare the hypoglycemic, hypolipidemic and hepatoprotective effects of the ethanolic extract of Asparagus racemosus (EEAR) Linn. alone and combinedly with conventional antidiabetic agents (gliclazide and pioglitazone) in alloxan-induced diabetic rats. Diabetes was induced in male Wister albino rats by the administration of single intra-peritoneal injection of alloxan monohydrate (120 mg/kg b.w.). Effect of oral administration of two different doses of EEAR (200 and 400 mg/kg b.w.), gliclazide (10 mg/kg b.w.) and pioglitazone (10 mg/70kg/b.w.) alone for 2 weeks and a combination of EEAR (200 mg/kg b.w.) with either gliclazide (10 mg/kg b.w.) or pioglitazone (10 mg/70kg/b.w.) for 2 weeks were examined on hypoglycemic activity on 0th, 5th, 10th and 14th day of treatment. After 2 weeks of treatment, hypolipidemic and hepatoprotective effects were estimated by serum biochemical markers such as total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), high density lipoprotein (HDL), serum glutamate oxaloacetate transaminases (SGOT), serum glutamate pyruvate trans-aminases (SGPT) and total protein (TP) with the help of commercially available kits. The survival rate, body weight and organ weight were also measured. Alloxan treatment resulted in persistent hyperglycemia, hyperlipidemia and liver dysfunction in rats. Treatment with EEAR at different doses improved hyperglycemia significantly (p < 0.05, p < 0.01, p < 0.001; p < 0.05, p < 0.01; p < 0.05) by reducing the blood glucose levels in rats on 10th and 14th day of treatment in a dose-dependent mood when compared to the disease control rats, gliclazide treated rats and pioglitazone treated rats. The combination therapy significantly (p < 0.001; p < 0.01, p < 0.001; p < 0.05, p < 0.01, p < 0.001) promoted the glucose-lowering activity on 5th, 10th and 14th day of treatment as compared to that of disease control rats, gliclazide treated rats and pioglitazone treated rats. Proposed adjunct therapy also markedly (p < 0.001; p < 0.01, p < 0.001) improved serum TG, HDL and LDL level with insignificant change in VLDL and TC level while comparing with groups receiving gliclazide treated rats and pioglitazone treated rats. Administration of different doses of
Investigation effect of pioglitazone, glimepiride, nobivolol, valsartan and hesperidine on glucose, HbA1c and blood pressure in experimentally induced myocardial infarction in type 2 diabetic rats
Jagdish Kakadiya, Jigar Brahmbhatt, Nehal Shah
International Journal of Research in Pharmaceutical Sciences , 2010,
Abstract: Present study was designed to evaluate effect some synthetic drugs and some herbal compound on Glucose, HbA1c and Systolic and diastolic blood pressure in isoproterenol induced myocardial infarction in normal and Streptozotocin-Nicotinamide induced diabetic in rats. Pioglitazone (10 mg/kg, p.o), Glimepiride (0.5 mg/kg, p.o), Nobivolol (2 mg/kg, p.o), Valsartan (8 mg/kg, p.o) and Hesperidin (100 mg/kg, p.o) were administered for 28 days in rats injected with single dose of Streptozotocin (65 mg/kg, i.p, STZ) and Nicotinamide (12mg/kg, i.p, NIC) and after isoproterenol (200 mg/kg, s.c.) induced myocardial infarction in rats on 29th and 30th day. At the end of experimental period (i.e. on the day 31) serum sample were collected, and glucose, HbA1c were find out and measurement of systolic and diastolic blood pressure. Administration of STZ–NIC in rats showed a significant (p<0.001) increased in the levels of serum glucose and glycosylated hemoglobin (HbA1c) and significant (p<0.01) increased in the level systolic and diastolic blood pressure as compared to respective control groups. Treatment with Pioglitazone, Glimepiride and Hesperidin significantly (P<0.05) decreased HbA1c, glucose, systolic and diastolic blood pressure but treatment with Nobivolol and Valsartan significantly (p<0.01) decreased without change on glucose and HbA1c. This study concluded that Pioglitazone, Glimepiride and Hesperidin may show reduced diabetes marker and systolic and diastolic blood pressure but Nobivolol and Valsartan may show reduced only systolic and diastolic blood pressure on experimentally induced myocardial infarction in type 2 diabetic rats.
Pioglitazone does not modify ANP levels of type 2 diabetic patients  [PDF]
Stefano Benedini, Paolo Villa, Livio Luzi, Maurizio Bevilacqua
World Journal of Cardiovascular Diseases (WJCD) , 2012, DOI: 10.4236/wjcd.2012.24043
Abstract: Background: The atrial natriuretic peptide (ANP) regulates fluid volume redistribution between heart and the pulmonary vessels. In diabetic patients the physiological action of ANP appears to be seriously altered. Methods: 12 subjects (gender 6M/6F, age 47 ± 2 years, BMI 29.1 ± 0.1 kg/m2), with type 2 diabetes and under stable conditions, were studied after one month of pioglitazione treatment (30 mg/die) by means of isotonic blood volume expansion. Results: After one month of pioglitazone treatment the meta- bolic profile of the subjects improved (decrease dia- stolic blood pressure: p = 0.05, total cholesterol: p = 0.01, triglycerides: p = 0.03 and blood glucose: p = 0.01) as the expansion of their plasma volume was found associated with the decrease of hematocrit (p < 0.05). The statistical comparison before versus after pioglitazone showed a significant decrease in the ba- sal aldosterone levels post-treatment (p < 0.04). Nonetheless ANP plasma levels were similar before and after therapy. Conclusions: The inappropriately high concentrations of ANP induced by hyperglyce-mia and the abnormal responses to a physiological sti- mulus like an isotonic blood volume expansion are not reverted by one month of pioglitazone. This is in contrast with the brisk improvement of the metabolic profile seen for the same period of treatment. ANP secretion is modified by fluid load in diabetic patients. This anomaly is not reverted by pioglitazone.
Effect of Peroxisome Proliferator-Activated Receptor Gamma Agonist (Pioglitazone) and Methotrexate on Disease Activity in Rheumatoid Arthritis (Experimental and Clinical Study)
Dina Shahin, Ehab El Toraby, Hala Abdel-Malek, Vivian Boshra, Ayman Z. Elsamanoudy and Dalia Shaheen
Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders , 2012, DOI: 10.4137/CMAMD.S5951
Abstract: Objective: To investigate the combined effect of both pioglitazone and methotrexate on disease activity of rheumatoid arthritis in a biphasic study; experimental and clinical. Methods: Experimentally: 50 rats were divided into 5 equal groups; controls, experimental arthritis, methorexate treated (0.1 mg/Kg daily), pioglitazone-treated (10 mg/kg daily), and methotrexate and pioglitazone treated. Clinically: forty-nine diabetic rheumatoid arthritis patients were included. Patients group consisted of 28 patients and they received pioglitazone 30 mg orally beside their usual treatment. Control group consisted of 21 patients and they continued their usual treatment plus placebo. Disease activity was assessed using DAS28 score. Patients were followed up for 3 months. Results: Pioglitazone produced a significant improvement of serum oxidative stress parameters (P < 0.05), and inflammatory cytokines in the treated arthritic group (P < 0.05). Clinically, the pioglitazone treated group showed significant improvement in DAS28 (P = 0.001) and C-reactive protein (P< 0.0001) compared to placebo group. Conclusion: The concomitant use of the PPAR γ agonist pioglitazone and methotrexate appears to be promising therapeutic strategy for rheumatoid arthritis patients.
Severe macular edema induced by pioglitazone in a patient with diabetic retinopathy: a case study  [cached]
Toshiyuki Oshitari,Noriko Asaumi,Masaru Watanabe,Ken Kumagai
Vascular Health and Risk Management , 2008,
Abstract: Toshiyuki Oshitari1, Noriko Asaumi1, Masaru Watanabe1, Ken Kumagai1, Yoshinori Mitamura1,21Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba, Japan; 2Department of Ophthalmology and Visual Science, Chuo-ku, Chiba, JapanAbstract: We report a case of severe diabetic macular edema (DME) that developed after pioglitazone was used by a patient with proliferative diabetic retinopathy. A 30-year-old woman with poorly controlled type 2 diabetes mellitus visited our clinic in 2004. She had moderate pre-proliferative diabetic retinopathy OU. Because of the rapid progression of the diabetic retinopathy, she received pan-retinal photocoagulation in both eyes. Two weeks before using pioglitazone, her visual acuity was 0.9 OD and 0.7 OS. On October 2007, pioglitazone was prescribed by her internist because of poorly controlled blood glucose level. Two weeks later, her body weight increased, and her face became edematous. Her visual acuity decreased to 0.5 OU, and ophthlamoscopy showed severe DME in both eyes. Two weeks after stopping pioglitazone, her visual acuity improved to 0.8 OD and 0.5 OS, but the DME was still severe in the optical coherence tomographic images. Then, one half the usual dose (25 mg) of spironolactone, a diuretic, was given and her macular edema was resolved. Her final visual acuity improved to 0.9 OD and 0.7 OS. We recommend that when a patient taking pioglitazone complains of decreased vision, the physician should promptly consult an ophthalmologist.Keywords: pioglitazone, diabetic macular edema, spironolactone, optical coherence tomography
Pioglitazone enhances collateral blood flow in ischemic hindlimb of diabetic mice through an Akt-dependent VEGF-mediated mechanism, regardless of PPARγ stimulation
Federico Biscetti, Giuseppe Straface, Vincenzo Arena, Egidio Stigliano, Giovanni Pecorini, Paola Rizzo, Giulia De Angelis, Luigi Iuliano, Giovanni Ghirlanda, Andrea Flex
Cardiovascular Diabetology , 2009, DOI: 10.1186/1475-2840-8-49
Abstract: By using a hindlimb ischemia murine model, in this study we have found that pioglitazone restores the blood flow recovery and capillary density in ischemic muscle of diabetic mice and that this process is associated with increased expression of Vascular Endothelial Growth Factor (VEGF). Importantly, these beneficial effects are abrogated when endogenous Akt is inhibited; furthermore, the direct activation of PPARγ, with its selective agonist GW1929, does not restore blood flow recovery and capillary density. Finally, an important collateral vessel growth is obtained with combined treatment with pioglitazone and selective PPARγ inhibitor GW9662.These data demonstrate that Akt-VEGF pathway is essential for ischemia-induced angiogenic effect of pioglitazone and that pioglitazone exerts this effect via a PPARγ independent manner.Diabetes mellitus is commonly associated with both microvascular and macrovascular complications such as coronary artery disease, cerebrovascular events, severe peripheral vascular disease, nephropathy and retinopathy [1]. Vascular function in diabetes has been studied extensively in both animal models and humans [2-4], and impaired endothelium-dependent vasodilatation has been documented as a consistent finding in animal models of diabetes induced by alloxan or streptozotocin [5,6]. Consistently, in vivo studies have confirmed that hyperglycemia directly induces endothelial dysfunction both in diabetic and healthy subjects [7]. Moreover an experimental animal model has shown a decreased ability of diabetic mice in restoring the blood flow and the capillarity density after hind-limb ischemia [8]. Thiazolidinedione derivatives (TZDs), such as pioglitazone, troglitazone and rosiglitazone, are indicated for therapy of type 2 diabetes mellitus (T2DM). They have been demonstrated to be effective alone or in combination with a sulfonylurea, metformin, or insulin. Pioglitazone is an insulin sensitizer that promotes glucose metabolism without increasing
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