Anti-hyperglycemic effect of a thiazolidinedione analogue and its role in ameliorating oxidative stress in alloxan-induced diabetic rats

Dr. B.R. Ambedkar Centre For Biomedical Research, University of Delhi, Old Delhi, NCT, India
Life Sciences (Impact Factor: 2.7). 03/2007; 80(12):1135-42. DOI: 10.1016/j.lfs.2006.12.004
Source: PubMed


Thiazolidinediones (TZDs) are a new class of antidiabetic drugs, having an insulin sensitizing effect in patients with type 2 diabetes. The contribution of oxidative stress from the standpoint of lipid and protein damage, alteration in endogenous antioxidant enzymes and effects of newly synthesized compounds, 5-[4-2-(6,7-Dimethyl-1,2,3,4-tetrahydro-2-oxo-4-quinoxalinyl)ethoxy]phenyl]methylene]thiazolid- ine-2,4-dione, (C(1)) in normal/alloxan-induced diabetic rats form the focus area of this study. Its effect was compared to two well-known TZDs, namely pioglitazone and rosiglitazone. It has been concluded from results that after thirty days of administration of C(1), Pg and Rg in alloxan-induced diabetic animal groups, the blood glucose level decreased, more remarkably in C(1) treated group. Also oxidative damage has been studied by estimating hepatic superoxide dismutase (SOD) activity, which was found to be increased (p<0.001 vs. control). An inverse change in SOD values between hepatic and pancreatic/kidney tissues were observed. Treatment with the test compounds lowered the activity of SOD in liver while increased its activity in kidney and pancreas. Similar normalizing effect of C(1) on liver, pancreatic and renal catalase (CAT)/ glutathione peroxidase (GPx) activities were pronounced in diabetic rats (p<0.001 vs. diabetic rats). Decreased reduced glutathione (GSH) content, found in diabetic animals, was significantly elevated to normal levels by C(1) treatment. The treatment with C(1) also decreased the levels of nitric oxide and increased the activities of glutathione-s-transferase and glutathione reductase, as compared to diabetic animals. Evidence of oxidative damage to lipids and proteins was shown through the quantification of protein carbonyl (in tissues) and malondialdehyde levels (both serum and tissues). It was observed that the protein/lipid damage in diabetic rats was improved by treatment with C(1). Total antioxidant activity (TAA) was found to be enhanced in C(1) treated rats (p>0.05 vs. group3, p<0.001 vs. group2, p<0.001 vs. group 4). These results suggest that the newly synthesized TZD derivative (C(1)) has a potential to act as antihyperglycemic and antioxidant agent. In addition, for all parameters checked, it has better efficacy than rosiglitazone and is as effective as pioglitazone.

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    • "The instigation in the levels of free radicals in alloxan-diabetic rats and the abatement in these levels after administration of alloxan-diabetic rats with SCEE are in concurrence with the findings by Baynes and Thorpe [49], Kumari and Augusti [50], Sheweita et al. [51], Anwar and Meki [52], and Campos et al. [53]. Moreover, it was noted that a single treatment of alloxan processed a reduction in the action of the liver (SOD, GSR, GPX, GST, and GR) throughout the advancement of alloxan induced diabetes mellitus [54]. "
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    ABSTRACT: Jurinea dolomiaea Boiss., family Compositae, is amedicinally important plant of alpine region. Its tuberous roots are used in various ailments in folk medicine. This study was undertaken to estimate total phenolic (TPC) and total flavonoid contents (TFC) and to determine anti-free radical potential by diverse in vitro antioxidant assays. Crude methanol extract (JDME) was fractionated into nhexane (JDHE), chloroform (JDCE), ethyl acetate (JDEE), n-butanol (JDBE), and aqueous (JDAE) fractions.The results indicated that JDEE and JDCE constituted the highest amount of TFC (807 ± 7.2mg rutin equivalent/g sample) and TPC (757 ± 9.4 mg gallic acid equivalent/g sample), respectively. Significant correlation of TFC with IC50 values was recorded for ∙OH (𝑅 2 = 0.91), H2O2 (𝑅 2 = 0.82), and ABTS (𝑅 2 = 0.82) assay. It could bemade clear that JDEEwas themost potent in antioxidant activity as compared to others, with generally lower IC50 values for DPPH (41.1 ± 1.0 𝜇g/mL), ABTS (46.7 ± 0.6 𝜇g/mL), H2O2 (42.2 ± 0.9 𝜇g/mL), ∙OH (61.1±1.1 𝜇g/mL),O2 − (152±1.1 𝜇g/mL), and antilipid peroxidation (54.3±1.6 𝜇g/mL).HPLC chromatogramof JDEE revealed the presence of catechin, caffeic acid, and rutin. The results indicated the antioxidant activities of J. dolomiaea roots and merit further investigations for their use in oxidative stress related disorders.
    Full-text · Article · Jul 2014 · BioMed Research International
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    • "Oxidative stress is implicated in the pathogenesis of several diseases, such as DM, polycystic ovary syndrome, gastric injury, and atherosclerosis (4-6). It has been shown that paraoxonase reduces H2O2, a major reactive species produced during oxidative stress (2). "
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    ABSTRACT: Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1 kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4 mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.
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    • "With regard to this report, RSG may indicate its full effect on blood glucose at 12th week. In our previous studies, it was indicated that the effects of treatment with RSG on the body weight of diabetic rats was significant [18], but treatment of diabetic rats with RSG (4 mg/kg/day) was caused a significant increase compared with diabetic rats by the end of the treatment period [24]. In our study, statistically significant increases in body weight were observed group B-treated diabetic rats. "
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    ABSTRACT: In this study, we tested the hypothesis that rosiglitazone (RSG) with insulin is able to quench oxidative stress initiated by high glucose through prevention of NAD(P)H oxidase activation. Male albino Wistar rats were randomly divided into an untreated control group (C), a diabetic group (D) that was treated with a single intraperitoneal injection of streptozotocin (45 mg kg(-1)), and rosiglitazone group that was treated with RSG twice daily by gavage and insulin once daily by subcutaneous injection (group B). HbA1c and blood glucose levels in the circulation and malondialdehyde and 3-nitrotyrosine levels in left ventricular muscle were measured. Treatment of D rats with group B resulted in a time-dependent decrease in blood glucose. We found that the lipid profile and HbA1c levels in group B reached the control group D rat values at the end of the treatment period. There was an increase in 3-nitrotyrosine levels in group D compared to group C. Malondialdehyde and 3-nitrotyrosine levels were found to be decreased in group B compared to group D (P < 0.05). Our data suggests that the treatment of diabetic rats with group B for 8 weeks may decrease the oxidative/nitrosative stress in left ventricular tissue of rats. Thus, in diabetes-related vascular diseases, group B treatment may be cardioprotective.
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