Ameliorating effects of troxerutin on nickel-induced oxidative stress in rats

Abstract

Objective

This study investigates the effects of troxerutin on nickel (Ni)-induced oxidative stress in rats.

Methods

Nickel as nickel sulfate (20 mg/kg body weight (b.w.)) was administered intraperitoneally for 20 days to induce toxicity in the subject rats. The levels of stress markers AST, ALT, ALP, LDH, and GGT in the hepatic tissue were significantly increased while a decrease in the levels of enzymic and non-enzymic antioxidants was observed in Ni intoxicated rats.

Results

Oral administration of troxerutin along with Ni for 20 days in a dose-dependent manner significantly reverted the stress markers in the liver tissue to near normal level. Troxerutin exhibited significant protection at 100 mg/kg b.w. Histopathological studies also supported the above findings.

Conclusions

Thus, we conclude that troxerutin preserved the histo-architecture and ameliorated stress markers in the liver tissue of Ni-intoxicated rats.     

Role of oxidative stress in experimental sepsis and multisystem organ dysfunction

Massive increase in radical species can lead to oxidative stress, promoting cell injury and death. This review focuses on experimental evidence of oxidative stress in critical illnesses, sepsis and multisystem organ dysfunction. Oxidative stress could negatively affect organ injury and thus overall survival of experimental models. Based on this experimental evidence, we could improve the rationale of supplementation of antioxidants alone or in combination with standard therapies aimed to reduce oxidative stress as novel adjunct treatment in critical care.     

Tryptophan loading induces oxidative stress

In previous studies tryptophan loads have been administered to human subjects in order to raise central levels of 5-hydroxytryptamine (5HT) and assess the effects of 5HT on behaviour and mood. However, tryptophan is metabolised primarily along the oxidative kynurenine pathway. In this study a 6 g oral tryptophan load was administered to 15 healthy volunteers and the levels of kynurenines and lipid peroxidation products (indicative of oxidative stress) were measured. The results demonstrate that tryptophan loading produces a highly significant increase in lipid peroxidation products in parallel with increased kynurenines. The oxidative stress may result from the generation of quinolinic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid, all of which are known to have the ability to generate free radicals. The results may have implications for the use of tryptophan loading in psychiatric practice, and for the chronic use of diets high in tryptophan.     

Calcium microdomains and oxidative stress

The phenomenon of calcium microdomains is firmly established in the field of subcellular physiology. These regions of localized, transient calcium increase are exemplified by the spontaneous 'sparks' released through the ryanodine receptor in myocytes, but include subplasmalemmal microdomains, focal calcium oscillations and microdomains enclosed within organelles, such as the endoplasmic reticulum, golgi and mitochondria. Increasing evidence suggests that oxidative stress regulates both the formation and disappearance of microdomains. Calcium release channels and transporters are all modulated by redox state, while several mechanisms that generate oxidative or nitrosative stress are regulated by calcium. Here, we discuss the evidence for the regulation of calcium microdomains by redox state, and, by way of example, demonstrate that the frequency of calcium sparks in cardiomyocytes is increased in response to oxidative stress. We consider the evidence for the existence of analogous microdomains of reactive oxygen and nitrogen species and suggest that the refinement of imaging techniques for these species might lead to similar concepts. The interaction between Ca(2+) microdomains and proteins that modulate their formation results in a complex and dynamic, spatial signaling mechanism, which is likely to be broadly applicable to different cell types, adding new dimensions to the calcium signaling 'toolkit'.     

Aluminum-induced oxidative stress in maize

The relation between Al-toxicity and oxidative stress was studied for two inbred lines of maize (Zea mays L.), Cat100-6 (Al-tolerant) and S1587-17 (Al-sensitive). Peroxidase (PX), catalase (CAT) and superoxide dismutase (SOD) activities were determined in root tips of both lines, exposed to different Al(3+) concentrations and times of exposure. No increases were observed in CAT activities in either line, although SOD and PX were found to be 1.7 and 2.0 times greater than initial levels, respectively, in sensitive maize treated with 36 microM of Al(3+) for 48 h. The results indicate that Al(3+) induces the dose- and time dependent formation of reactive oxygen species (ROS) and subsequent protein oxidation in S1587-17, although not in Cat100-6. After exposure to 36 microM of Al(3+) for 48 h, the formation of 20+/-2 nmol of carbonyls per mg of protein was observed in S1587-17. The onset of protein oxidation took place after the drop of the relative root growth observed in the sensitive line, indicating that oxidative stress is not the primary cause of root growth inhibition. The presence of Al(3+) did not induce lipid peroxidation in either lines, contrasting with the observations in other species. These results, in conjunction with the data presented in the literature, indicate that oxidative stress caused by Al may harm several components of the cell, depending on the plant species. Moreover, Al(3+) treatment and oxidative stress in the sensitive maize line induced cell death in root tip cells, an event revealed by the high chromatin fragmentation detected by TUNEL analysis.     

Protective effect of arginine on oxidative stress in transgenic sickle mouse models

Sickle cell disease (SCD) is characterized by reperfusion injury and chronic oxidative stress. Oxidative stress and hemolysis in SCD result in inactivation of nitric oxide (NO) and depleted arginine levels. We hypothesized that augmenting NO production by arginine supplementation will reduce oxidative stress in SCD. To this end, we measured the effect of arginine (5% in mouse chow) on NO metabolites (NOx), lipid peroxidation (LPO), and selected antioxidants in transgenic sickle mouse models. Untreated transgenic sickle (NY1DD) mice (expressing  75% β^S-globin of all β-globins; mild pathology) and knockout sickle (BERK) mice (expressing exclusively hemoglobin S; severe pathology) showed reduced NOx levels and significant increases in the liver LPO compared with C57BL mice, with BERK mice showing maximal LPO increase in accordance with the disease severity. This was accompanied by reduced activity of antioxidants (glutathione, total superoxide dismutase, catalase, and glutathione peroxidase). However, GSH levels in BERK were higher than in NY1DD mice, indicating a protective response to greater oxidative stress. Importantly, dietary arginine significantly increased NOx levels, reduced LPO, and increased antioxidants in both sickle mouse models. In contrast, nitro-L-arginine methylester, a potent nonselective NOS inhibitor, worsened the oxidative stress in NY1DD mice. Thus, the attenuating effect of arginine on oxidative stress in SCD mice suggests its potential application in the management of this disease.     

Role of lupeol and lupeol linoleate on lipemic-oxidative stress in experimental hypercholesterolemia

Epidemiological studies have shown that there is a positive correlation between the incidence of coronary heart disease (CHD) and the blood cholesterol level. To study the effect of plant derived triterpene, lupeol and its ester lupeol linoleate, on blood lipid status and oxidant stress in heart and hemolysate, male albino Wistar rats were fed high cholesterol diet (normal rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days. A significant increase (p<0.05) in plasma total cholesterol (4.22 fold) and triglycerides (1.7 fold) was observed in HCD fed rats, along with elevated LDL (3.56 fold) and VLDL (1.99 fold) cholesterol and decreased HDL cholesterol (34.14%). Treatment with lupeol and its derivative normalized the lipid profile. The significant increase (p<0.05) in lipid peroxidation (LPO) was paralleled by significantly diminished (p<0.05) activities of antioxidant enzymes (SOD, CAT and GPx) and decreased (p<0.05) concentration of antioxidant molecules (GSH, Vit C and Vit E) in cardiac tissue and hemolysate of HCD fed rats. The oxidative tissue injury in hypercholesterolemic rats was substantiated by the increase in cardiac marker, serum CPK and the drop in its activity in the heart tissue. Lupeol and lupeol linoleate treatment decreased the LPO levels and increased enzymatic and nonenzymatic antioxidants. CPK activity in the treated group was comparable with that of the control. These observations highlight the beneficial effects of the triterpene, lupeol and its linoleate ester derivative, in ameliorating the lipidemic-oxidative abnormalities in the early stage of hypercholesterolemic atherosclerosis.     

Genistein abrogates pre-hemolytic and oxidative stress damage induced by 2,2'-Azobis (Amidinopropane)

The pre-hemolytic mechanism induced by free radicals initiated from water-soluble 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) and its reversal by genistein was investigated in human erythrocytes. The time course of K+ efflux compared to the occurrence of hemolysis suggests that AAPH-induced hemolysis occurs indirectly via pore formation and band 3 oxidation as expected. However, genistein inhibited hemolysis, LDH release and membrane protein oxidation but not K+ efflux. This indicated that erythrocyte protein oxidation possibly in the hydrophobic core plays a significant role in the membrane pre-hemolytic damage. Chemiluminescence (CL) analysis carried out in non-lysed erythrocytes treated with AAPH showed a dramatic increase in CL indicating both reduced levels of antioxidants and increased membrane lipid peroxide. The V0 value was also increased up to 6 times, denoting a high degree of membrane peroxidation very early in erythrocyte membrane damage. The whole process was inhibited by genistein in a dose-dependent manner. These results indicate that the genistein inhibited both hemolysis and pre-hemolytic damage and also hindered membrane lipid peroxide formation and protein oxidation. In addition, it is suggested that pre-hemolytic damage is mediated mainly by the oxidation of both phospholipid and protein located in the deeper hydrophobic region of the membrane.     

微囊藻细胞抽提物亚慢性暴露导致小鼠肝脏氧化应激

研究了微囊藻细胞抽提物亚慢性暴露对小鼠肝脏抗氧化系统的影响.采用腹腔注射进行连续染毒28d,染毒组剂量为3.3μg micmcystins/kg体重.结果显示,超氧化物歧化酶、过氧化氧酶、谷胱甘肽过氧化物酶在第4周时发生显著性升高,提示微囊藻细胞抽提物激活了小鼠肝脏抗氧化系统.谷胱甘肽-S-转移酶和对照组相比也显著提高,表明谷胱甘肽-S-转移酶作为解毒Ⅰ相酶加快了对肝脏微囊藻毒素的清除.脂质过氧化产物丙二醛也显著升高,说明抗氧化系统未能清除微囊藻细胞抽提物对小鼠肝脏的氧化损伤,导致了氧化应激的产生.结果表明低剂量微囊藻细胞抽提物长时间暴露能够导致小鼠肝脏氧化损伤.     

Effects of U83836E on nerve functions, hyperalgesia and oxidative stress in experimental diabetic neuropathy

Oxidative stress has been implicated to play an important role in the pathogenesis of diabetic neuropathy, which is the most common complication of diabetes mellitus affecting more than 50% of diabetic patients. In the present study, we have investigated the effect of U83836E [(-)-2-((4-(2,6-Di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl)methyl)-3,4-dihydro-2,3,7,8-tetramethyl-2H-1-benzopyran-6-ol, 2HCl], a potent free radical scavenger in streptozotocin (STZ)-induced diabetic neuropathy in rats. STZ-induced diabetic rats showed significant deficit in motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and thermal hyperalgesia after 8 weeks of diabetes induction, indicating development of diabetic neuropathy. Antioxidant enzyme (superoxide dismutase and catalase) levels were reduced and malondialdehyde (MDA) levels were significantly increased in diabetic rats as compared to the age-matched control rats, this indicates the involvement of oxidative stress in diabetic neuropathy. The 2-week treatment with U83836E (3 and 9 mg/kg, i.p.) started 6 weeks after diabetes induction significantly ameliorated the alterations in MNCV, NBF, hyperalgesia, MDA levels and antioxidant enzymes in diabetic rats. Results of the present study suggest the potential of U83836E in treatment of diabetic neuropathy.     

Protection of cells from oxidative stress by microsomal glutathione transferase 1

Rat liver microsomal glutathione transferase 1 (MGST1) is a membrane-bound enzyme that displays both glutathione transferase and glutathione peroxidase activities. We hypothesized that physiologically relevant levels of MGST1 is able to protect cells from oxidative damage by lowering intracellular hydroperoxide levels. Such a role of MGST1 was studied in human MCF7 cell line transfected with rat liver mgst1 (sense cell) and with antisense mgst1 (antisense cell). Cytotoxicities of two hydroperoxides (cumene hydroperoxide (CuOOH) and hydrogen peroxide) were determined in both cell types using short-term and long-term cytotoxicity assays. MGST1 significantly protected against CuOOH and against hydrogen peroxide (although less pronounced and only in short-term tests). These results demonstrate that MGST1 can protect cells from both lipophilic and hydrophilic hydroperoxides, of which only the former is a substrate. After CuOOH exposure MGST1 significantly lowered intracellular ROS as determined by FACS analysis.     

Oral administration of levan polysaccharide reduces the alloxan-induced oxidative stress in rats

This study aimed to evaluate the effect of a polysaccharide named levan, which was produced by new isolated bacteria, on oxidative stress and hyperglycemia in alloxan-induced diabetic rats. Levan polysaccharide was given in drinking water for 60 days at a daily dose equivalent to 2%. The oral administration of levan in diabetic rats caused a decrease in glucose level in plasma and an increase of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities in both pancreas and liver. Furthermore, a protective action against hepatic and pancreatic toxicity in diabetic rats was clearly observed. Furthermore, a significant decrease in hepatic and pancreatic indices toxicity was observed, i.e., alkalines phosphatases (ALP), aspartate and lactate transaminases (AST and ALT), lactate deshydrogenases (LDH) activities and the thiobarbituric acid-reactive substances (TBARs). These beneficial effects of levan were confirmed by histological findings in hepatic and pancreatic tissues of diabetic rats. This study demonstrates for the first time that levan is efficient in inhibiting hyperglycemia and oxidative stress induced by diabetes and suggests that administration of levan may be helpful in the prevention of diabetic complications associated with oxidative stress.     

On the potential increase of the oxidative stress status in patients with abdominal aortic aneurysm

Abstract

Background

Abdominal aortic aneurysm (AAA) is a major cause of preventable deaths in older patients. Oxidative stress has been suggested to play a key role in the pathogenesis of AAA. However, only few studies have been conducted to evaluate the blood oxidative stress status of AAA patients.

Methods and results

Twenty seven AAA patients (mean age of 70 years) divided into two groups according to AAA size (≤50 or >50 mm) were compared with an age-matched group of 18 healthy subjects. Antioxidants (vitamins C and E, β-carotene, glutathione, thiols, and ubiquinone), trace elements (selenium, copper, zinc, and copper/zinc ratio) and markers of oxidative damage to lipids (lipid peroxides, antibodies against oxidized patients, and isoprostanes) were measured in each subject. The comparison of the three groups by ordinal logistic regression showed a significant decrease of the plasma levels of vitamin C (P = 0.011), α-tocopherol (P = 0.016) but not when corrected for cholesterol values, β-carotene (P = 0.0096), ubiquinone (P = 0.014), zinc (P = 0.0035), and of selenium (P = 0.0038), as AAA size increased. By contrast, specific markers of lipid peroxidation such as the Cu/Zn ratio (P = 0.046) and to a lesser extent isoprostanes (P = 0.052) increased.

Conclusion

The present study emphasizes the potential role of the oxidative stress in AAA disease and suggests that an antioxidant therapy could be of interest to delay AAA progression.     

4-Hydroxynonenal induces oxidative stress and death of cultured spinal cord neurons

Primary spinal cord trauma can trigger a cascade of secondary processes leading to delayed and amplified injury to spinal cord neurons. Release of fatty acids, in particular arachidonic acid, from cell membranes is believed to contribute significantly to these events. Mechanisms of fatty acid-induced injury to spinal cord neurons may include lipid peroxidation. One of the major biologically active products of arachidonic acid peroxidation is 4-hydroxynonenal (HNE). The levels of HNE-protein conjugates in cultured spinal cord neurons increased in a dose-dependent manner after a 24-h exposure to arachidonic acid. To study cellular effects of HNE, spinal cord neurons were treated with different doses of HNE, and cellular oxidative stress, intracellular calcium, and cell viability were determined. A 3-h exposure to 10 microM HNE caused approximately 80% increase in oxidative stress and 30% elevation of intracellular calcium. Exposure of spinal cord neurons to HNE caused a dramatic loss of cellular viability, indicated by a dose-dependent decrease in MTS [3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-s ulfophenyl)- 2H-tetrazolium, inner salt] conversion. The cytotoxic effect of HNE was diminished by pretreating neurons with ebselen or N-acetylcysteine. These data support the hypothesis that formation of HNE may be responsible, at least in part, for the cytotoxic effects of membrane-released arachidonic acid to spinal cord neurons.     

Aortic coarctation induces oxidative stress in rat tissues

The purpose of this study was to evaluate the induction of oxidative stress in heart and erythrocytes from rats with abdominal aorta coarctation (Coa) compared with sham-operated normotensive controls (Sham). The group of Coa animals developed myocardial hypertrophy, showing heart homogenates markedly increased levels of reduced glutathione (48%), lipid peroxidation (148%) and activation of superoxide dismutase and glutathione peroxidase (189% and 37%, respectively), compared with controls. Other oxidative stress indicators were also altered in erythrocytes from Coa rats: increased protein carbonyl content (141%) and total glutathione level (349%) were determined. Inactivation of the antioxidant enzymes catalase (27%), superoxide dismutase (58%) and glutathione peroxidase (25%) was observed in erythrocytes from the Coa group. Taken jointly our results provide strong evidence for the production of oxidative stress in heart and erythrocytes from aortic coarcted rats.     

Repeated freezing induces oxidative stress and reduces survival in the freeze-tolerant goldenrod gall fly,Eurosta solidaginis

Freeze tolerant insects must not only survive extracellular ice formation but also the generation of reactive oxygen species (ROS) during oxygen reperfusion upon thawing. Furthermore, diurnal fluctuations in temperature place temperate insects at risk of being exposed to multiple freeze–thaw cycles, yet few studies have examined metrics of survival and oxidative stress in freeze-tolerant insects subjected to successive freezing events. To address this, we assessed survival in larvae of the goldenrod gall fly Eurosta solidaginis, after being subjected to 0, 5, 10, 20, or 30 diurnally repeated cold exposures (RCE) to −18 °C or a single freeze to −18 °C for 20 days. In addition, we measured indicators of oxidative stress, levels of cryoprotectants, and total aqueous antioxidant capacity in animals exposed to the above treatments at 8, 32, or 80 h after their final thaw. Repeated freezing and thawing, rather than time spent frozen, reduced survival as only 30% of larvae subjected to 20 or 30 RCE successfully pupated, compared to those subjected to fewer RCE or a single 20 d freeze, of which 82% pupated. RCE had little effect on the concentration of the cryoprotectant glycerol (4.26 ± 0.66 μg glycerol·ng protein⁻¹ for all treatments and time points) or sorbitol (18.8 ± 2.9 μg sorbitol·mg protein⁻¹ for all treatments and time points); however, sorbitol concentrations were more than twofold higher than controls (16.3 ± 2.2 μg sorbitol·mg protein⁻¹) initially after a thaw in larvae subjected to a single extended freeze, but levels returned to values similar to controls at 80 h after thaw. Thawing likely produced ROS as total aqueous antioxidant capacities peaked at 1.8-fold higher than controls (14.7 ± 1.6 mmol trolox·ng protein⁻¹) in animals exposed to 5, 10, or 20 RCE. By contrast, aqueous antioxidant capacities were similar to controls in larvae subjected to 30 RCE or the single 20 d freeze regardless of time post final thaw, indicating these animals may have had an impaired ability to produce primary antioxidants. Larvae lacking an antioxidant response also had elevated levels of oxidized proteins, nearly twice that of controls (21.8 ± 3.2 mmol chloramine-T·mg protein⁻¹). Repeated freezing also lead to substantial oxidative damage to lipids that was independent of aqueous antioxidant capacity; peroxides were, on average, 5.6-fold higher in larvae subjected to 10, 20 or 30 RCE compared to controls (29.1 ± 7.3 mmol TMOP·μg protein⁻¹). These data suggest that oxidative stress due to repeated freeze–thaw cycles reduces the capacity of E. solidaginis larvae to survive freezing.     

Adaptation to oxidative stress and impact of chronic oxidative stress on immunity in heat-stressed broilers

1. Glutathione peroxidase activity and serum malondialdehyde of heat-stressed broilers were increased in the early period of heat exposure, and then these parameters decreased.

2. The lesion scores of bursa of Fabricius in heat-stressed broilers were increased and decreased in accordance with the activity of glutathione peroxidase and serum malondialdehyde.

3. High environmental temperature had not affected relative bursa of Fabricius weight and NDV-HI titer of heat-stressed broilers.

4. We concluded that heat-stressed broilers could adapt to oxidative stress, and environmental temperature set at 38±2 °C had not affected humoral immunity.

Effect of methanol-induced oxidative stress on the neuroimmune system of experimental rats

It is well known that the nervous system has increased susceptibility to methanol intoxication. The present study reveals the effect of methanol intoxication on antioxidant status, lipid peroxidation and DNA integrity in hypothalamic-pituitary-adrenal (HPA) axis organs and spleen. Non-specific and specific immune functions were analyzed. In addition, open field behavior, plasma corticosterone level and blood methanol level were estimated. Male Wistar albino rats were intoxicated with methanol (2.37 g/kg b.wt., i.p.) for 1 day, 15 and 30 days. Administration of methanol showed significant increase in enzymatic (superoxide dismutase, catalase, glutathione peroxidase), non-enzymatic (reduced glutathione and Vitamin C) antioxidants and lipid peroxidation (LPO) in hypothalamus and adrenal gland of day 1 group. However, decrease in enzymatic and non-enzymatic antioxidants with concomitant increase in LPO level were observed in 15 and 30 days groups. Plasma corticosterone level was significantly increased in day 1 and 15 days groups whereas, 30 days methanol intoxication group showed considerable decrease in corticosterone level compared with control animals. Cell-mediated immune response of footpad thickness was significantly decreased with an increased leukocyte migration inhibition. Humoral immune response of antibody titers was elevated in methanol-intoxicated groups. Neutrophil functions, adherence and phagocytic index (PI) were found to be significantly decreases. Furthermore, significant increase in the avidity index and nitro blue tetrozolium reduction was observed in the methanol exposed animals. Day 1 methanol exposed group showed increased PI compared to the control ones. Methanol exposure for 30 days showed an increased DNA fragmentation in the hypothalamus, adrenal glands, and spleen. In conclusion, exposure to methanol-induced oxidative stress disturbs the HPA-axis function altering the level of corticosterone, which lead to varied non-specific and specific immune response in experimental rats.     

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

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.