Resveratrol Suppresses T0901317-Induced Hepatic Fat Accumulation in Mice

Liver X receptor (LXR) has been identified as a potential target for treatment of atherosclerosis and diabetes. Activation of LXR, however, is associated with increased lipogenesis and fat accumulation in the liver. The objective of the current study was to examine the effect of resveratrol on LXR activator-induced fat accumulation in liver using mice as an animal model. Three groups of C57BL/6 mice were studied. Animals in group 1 were treated with T0901317, a potent activator of LXR in mice. Animals in group 2 served as the control and were treated with carrier solution and those in group 3 were treated with T0901317/resveratrol combination. Using histochemical and biochemical methods, we demonstrate that resveratrol treatment significantly suppressed fat accumulation in the liver induced by T0901317. In addition, resveratrol completely blocked elevation of blood levels of triglyceride and cholesterol and reduced blood glucose level. Quantitative PCR analysis revealed that resveratrol treatment did not change the mRNA levels of abca1, abcg1, cyp7a1, srebp-1c, chrebp, and acc genes compared to that of animals treated with T0901317 alone but reduced pepck and g6p gene expressions. Immunohistochemistry and Western blot analyses show resveratrol treatment activated AMP-activated protein kinase (AMPK) and increased phosphorylation of acetyl-CoA carboxylase. Treatment with T0901317 on hepatocytes increased intracellular fat accumulation and this increase was suppressed by resveratrol; the suppressive effect of resveratrol was greatly repressed by Compound C which is an inhibitor of AMPK. Collectively, these data suggest that resveratrol blocks T0901317-induced lipid accumulation in the liver and can be considered for inclusion into the treatment of diseases involving activation of liver X receptor.     

Telmisartan Treatment Ameliorates Memory Deficits in Streptozotocin-Induced Diabetic Mice via Attenuating Cerebral Amyloidosis

Telmisartan, an angiotensin II type 1–receptor blocker (ARBs), has been reported to exert beneficial effects on the central nervous system (CNS). However, the effect of telmisartan on cognitive impairment associated with type 1 diabetes is not well known. Here, we examined the possibility that telmisartan could improve memory function in a type 1 diabetic mouse model, streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice subjected to the Morris Water Maze (MWM) task exhibited a significant decline of spatial learning and memory. Oral administration of telmisartan at two nonhypotensive doses (0.7 or 0.35 mg/kg) significantly improved memory deficits in STZ-induced diabetic mice. Telmisartan treatment markedly reduced Aβ₄₂, APP, BACE1, RAGE, and NF-κB p65 of the hippocampus and cortex, but did not beneficially affect hyperglycemia and hypoinsulinemia in the STZ-induced diabetic mice compared with untreated diabetic mice. Taken together, our findings suggest that telmisartan ameliorates memory deficits in type 1 diabetic mice, at least partly because of attenuation of amyloidosis in the brain.     

钒对糖尿病小鼠实验治疗作用的研究

微量元素钒(Vanadium,V)有多种氧化价态.不同的钒化合物.其生物活性不同.我们比较了Na-VO_3与VOSO_4的降血糖作用.前者稍强.但VOSO_4的毒性较低.VOSO_4虽不影响正常动物的血糖.但可显著降低高血糖动物的血糖,其降血糖机制与胰岛素类似.     

One-year Treatment of Streptozotocin-Induced Diabetic Rats with Vanadyl Sulphate

Streptozotocin-diabetic and non-diabetic rats were given various concentrations of vanadyl sulphate in drinking water for one year. It was found that vanadyl sulphate caused significant decreases in body weight gain and plasma insulin level in non-diabetic rats, but did not significantly alter fluid and food intakes or plasma levels of glucose, triglycerides, or cholesterol. In diabetic animals, vanadyl treatment significantly alleviated or prevented the occurrence of hyperglycaemia, hypoinsulinaemia, hyperphagia, polydipsia, hyperlipidaemia, or cataract formation, but the slower body weight gain was not improved. There were gradual decreases in the intake of the compound required to correct hyperglycaemia in the values of ED₅₀ with age of the rats. The beneficial effects of vanadyl treatment persisted 16 weeks following the withdrawal of the compound. It is concluded that vanadyl sulphate is an effective agent for chronic therapy of streptozotocin-induced diabetes in rats, and its prolonged use does not lead to the development of tolerance.     

An Investigation into the Effect of Sulfonylurea Glyburide on Glutathione Peroxidase Activity in Streptozotocin-Induced Diabetic Rat Muscle Tissue

• 1.Four weeks of glyburide (glibenclamide) treatment (5 mg/kg, orally) was administered in type II diabetic rats and the effect of such treatment was determined on muscle glutathione peroxidase (GPx) activity.
• 2.GPx activity was measured by a spectrophotometric method in which its activity was coupled to the oxidation of NADPH by glutathione reductase.
• 3.No statistically significant difference was found in muscle GPx activity between diabetic rats and controls.
• 4.There was a significant difference in GPx activity between glyburide-treated diabetic and nontreated diabetic groups and between glyburide-treated control and control groups.
• 5.The results of this study demonstrated that diabetes did not significantly alter skeletal muscle GPx activity in diabetic rats. However, glyburide may be an effective antioxidant agent in addition to its expected insulin-like effects.

     

Antidiabetic and Anti-oxidant Activity of Aegle marmelos Extract in Streptozotocin-Induced Diabetic Rats

The aqueous extract of Aegle marmelos Correa. fruits (AMFEt) was studied in normal and streptozotocin (STZ) diabetic rats and anti-lipid peroxidative activity was studied in hepatic and renal tissues in diabetic rats. Oral administration of AMFEt for 30 days (twice a day) prevented significantly the STZ-induced hyperglycaemia and hypoinsulinemia. The extract also produced a significant decrease in peroxidation products, viz., thiobarbituric acid reactive substances and hydroperoxides in diabetic rats. The activity of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase was found to be increased in the hepatic and renal tissues of diabetic animals treated with AMFEt. AMFEt, at a dose of 250?mg/kg, was more effective than glibenclamide and reversed all the values to near normal status. Thus, AMFEt exhibits antidiabetic and anti-oxidative activity in STZ-diabetic rats.     

胰高血糖素受体siRNA对糖尿病模型小鼠的降糖作用研究

目的:设计合成胰高血糖素受体(GCGR)基因的siRNA序列,并考察其对糖尿病模型小鼠的降糖作用。方法:根据siR-NA设计原理设计了3条靶向GCGR的siRNA序列(siRNA-1、siRNA-2、siRNA-3)。在建立了糖尿病模型小鼠以及血糖检测方法的基础上,检测一次性高压快速静脉注射给药后连续8d的血糖含量,以及给药后第2天腹腔注射葡萄糖后30、60、90、120min时血糖含量,并计算AUC值(糖耐量测试);同时设立非靶向siRNA组为对照。结果:3条靶向性siRNA给药后第1天小鼠血糖含量即明显下降,之后虽有所回升,但是与给药前比较仍有降低,而对照组则未出现血糖降低的现象,反而有所升高;在糖耐量试验中,siRNA-1、siRNA-2、siRNA-3序列组及对照组AUC分别为964.5、3216.1、2606.9、4173.9min·mmo·lL-1,前3组对葡萄糖的生物利用度显著更高。结论:设计合成的3条靶向GCGR的siRNA序列经静脉注射给药后,可较为有效地改善模型小鼠的高血糖症状。     

Free Radical Scavenging Activity of Calotropis gigantea on Streptozotocin-Induced Diabetic Rats

Swarnabhasma, an Ayurvedic preparation containing Calotropis gigantea R. Br. (Asclepiadaceae) is extensively used by Ayurvedic physicians for treatment of diabetes mellitus, bronchial asthma, rheumatoid arthritis and nervous disorders. In the present study, we report the effect of chloroform extracts of Calotropis gigantea leaf and flower on free radical scavenging activity, and lipid profile in streptozotozin-induced diabetic rats. The lipid peroxidation, superoxide dismutase, and catalase were measured in liver homogenate and serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, lipid profile were measured in blood serum. Administration of single dose of streptozotozin (55 mg/kg, i.p.) caused significant increases in lipid peroxidation, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, cholesterol and triglyceride levels, while superoxide dismutase and catalase levels were significantly decreased. Further, administration of chloroform extracts of Calotropis gigantea leaf and flower to streptozotocin-induced diabetes rats at a dose of 10, 20 and 50 mg/kg orally for 27 d lead to a significant decrease in lipid peroxidation, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, cholesterol and triglyceride levels. Consequently, superoxide dismutase and catalase levels were significantly increased. Glibenclamide was used as a positive control (10 mg/kg). It was observed that the effect of chloroform extracts of Calotropis gigantea on alkaline phosphatase, cholesterol, superoxide dismutase, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, levels are comparable to that of those produced by the positive control.     

车前子多糖对糖尿病小鼠氧化应激的影响

目的:研究车前子多糖(PSP)对实验性四氧嘧啶糖尿病小鼠氧化应激的影响。方法:60只昆明种小鼠随机抽取8只为对照组,其余动物于造模前饥饿24h,采用一次性腹腔注射四氧嘧啶,诱发形成实验性四氧嘧啶糖尿病小鼠动物模型,共有32只小鼠造模成功。随机分为模型组和各PSP给药组(P1、P2、P3组),每组8只。比色法测定丙二醛(MDA)、一氧化氮(NO)水平和一氧化氮合酶(NOS)活性及超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-PX)活性。观察PSP对上述各生化指标的影响。结果:与模型组比较,除了P1组血清、心脏SOD,血液CAT,心脏GSH-PX、肾脏NO和血清的NOS差异无统计学意义,小鼠血清和心脏的MDA水平均显著降低外,其他指标活性均显著升高。结论:PSP具有抗氧化效应及清除氧自由基的作用。     

Berberine Improves the Protective Effects of Metformin on Diabetic Nephropathy in db/db Mice through Trib1-dependent Inhibiting Inflammation

Pharmaceutical Research - Diabetic nephropathy (DN), one of severe diabetic complications in the diabetes, is the main cause of end stage renal disease (ESRD). Notably, the currently available...     

Evaluation of Antioxidant Potential of Terminalia chebula. Fruits Studied in Streptozotocin-Induced Diabetic Rats

Abstract

Oxidative stress is believed to be a pathogenic factor in the development of diabetic complications. Recently, we have reported the antidiabetic activity of Terminalia chebula. Retz. (Combretaceae) fruits on streptozotocin (STZ)-induced experimental diabetes. The current study was aimed to evaluate the antioxidant potential of Terminalia chebula. fruits on STZ-induced diabetic rats. Oral administration of ethanol extract of Terminalia chebula. fruit at a concentration of 200 mg/kg body weight for 30 days significantly controlled the alteration in the levels of thiobarbituric acid reactive substances, hydroperoxides, and both enzymatic and nonenzymatic antioxidants. In addition, the treatment also resulted in a significant decrease in the levels of blood glucose and glycosylated hemoglobin. The results are comparable with glibenclamide, a known hypoglycemic drug. The presence of biologically active ingredients in the fruit extract may be responsible for the antioxidant properties of the Terminalia chebula. fruits, which in turn may be partially responsible for its antidiabetogenic properties.     

Nitric Oxide Synthase Activity and l-Arginine Metabolism in the Retinas from Streptozotocin-Induced Diabetic Rats*

• 1.Nitric oxide synthase (NOS) activity was studied in the retinas from normal rats and in the retinas from two groups of streptozotocin-induced (8 days and 4 months) diabetic rats. In each animal group, the NOS activity was correlated to the concentration of amino acids related to L-arginine metabolism and to L-arginine uptake.
• 2.Retinas from both groups of streptozotocin-induced diabetes (8 days and 4 months) showed an increased NOS activity compared with the NOS activity in retinas from normal rats. In retinas lysate from normal rats, the NOS activity was most potently inhibited by NO-Arg (1 mM), whereas, in both groups of streptozotocin-induced diabetes, the NOS activity was most potently inhibited by the NOS inhibitor aminoguanidine (0.5 mM).
• 3.The basal levels of the amino acids related to L-arginine metabolism—namely, L-arginine, L-citrulline, L-ornithine and L-glutamine—in retinas from both groups of rats with streptozotocin-induced diabetes were decreased compared with the amino acid levels in retinas from normal rats.
• 4.The uptake of L-[³H]arginine in retinas from both groups of rats with streptozotocin-induced diabetes was increased compared with the uptake of of L-[³H]arginine in retinas from normal rats.

     

Antihyperglycemic Activity of Aqueous Root Extract of Rubia cordifolia. in Streptozotocin-Induced Diabetic Rats

Abstract

The aim of the current study was to examine the antidiabetic action of Rubia cordifolia. Linn (Rubiaceae) aqueous root extract (RCAREt) in streptozotocin (STZ)-induced diabetic rat model. STZ-induced diabetic rats were treated with RCAREt for 8 weeks (1 g kg^?1 b.w., orally per day). Serum glucose, total cholesterol and triglycerides, hematological parameters, and liver and kidney transaminases in normal, STZ diabetic, and RCAREt-treated diabetic rats were measured. The observed hyperglycemia, hypertriglyceridemia, enhanced transaminases of liver and kidney, hypochromic microcytic anemia, and loss of body weight in STZ diabetic rats were normalized by RCAREt treatment, whereas the hypercholesterolemia was not rectified. The beneficial effect of RCAREt treatment might be due to different types of active principles, each with a single or a diverse range of biological activities.     

螺旋藻多糖对糖尿病小鼠抗氧化能力的影响

腹腔注射四氧嘧啶（ＡＬＸ）２００mg/kg建立糖尿病模型小鼠,并随机分为４组,分别用螺旋藻多糖（ＰＳＰ）１００mg/kg、２００mg/kg及阳性对照药优降糖２mg/kg灌胃给药,糖尿病模型对照组则给等容积生理盐水,连续１４d后,分别测定各组小鼠血糖、血清ＳＯＤ活性、ＭＤＡ含量及全血ＧＳＨ－Ｐx活性与ＧＳＨ含量。结果与糖尿病模型对照组相比,ＰＳＰ能使ＡＬＸ所致糖尿病小鼠血糖降低（Ｐ＜０.０１）;血清ＳＯＤ活性、全血ＧＳＨ－Ｐx活性及ＧＳＨ一显著回升（Ｐ＜０.０１）;血清ＭＤＡ含量明显下降（Ｐ＜０.０１）。结果表明ＰＳＰ能降低ＡＬＸ性糖尿病小鼠高血糖并显著增强其抗氧化能力。提示ＰＳＰ降血糖作用的机制可能与其增强糖尿病鼠抗氧化能力有关。     

Effect of Rosiglitazone on Liver Structure and Function in Genetically Diabetic Akita Mice

Genetically diabetic Akita mice, kept on a high‐fat and high‐cholesterol diet, and treated with the peroxisome proliferator‐activated receptor‐γ agonist rosiglitazone (10 mg/kg per day during 4 months), displayed rosiglitazone‐induced side effects, similar to those observed in patients, including weight and fat gain and early signs of hypertrophic cardiomyopathy. As several cases of hepatotoxicity were reported in patients receiving rosiglitazone treatment, this study evaluated whether rosiglitazone also induced hepatotoxicity in these diabetic animals. Liver structure and function was analysed in wild‐type and rosiglitazone‐treated and untreated Akita mice, kept for 4 months on the high‐fat and high‐cholesterol diet. Decreased circulating levels of the liver enzymes aspartate and alanine aminotransferase and increased levels of alkaline phosphatases were observed upon rosiglitazone treatment, whereas liver weight was markedly increased. Rosiglitazone administration was associated with liver steatosis, as demonstrated by triglyceride accumulation. However, gene expression of steatosis markers in liver tissue was not markedly affected by rosiglitazone treatment, while expression of fatty acid transport protein was reduced by rosiglitazone treatment, suggesting an impairment of the fatty acid β‐oxidation pathway. mRNA expression of pro‐ and anti‐oxidant enzymes and liver 3‐nitrotyrosine content was not affected. Furthermore, gene and protein expression of macrophage markers and of cell adhesion molecules did not indicate progression to steatohepatitis, whereas an unaltered collagen deposition did not suggest steatofibrosis. In conclusion, rosiglitazone treatment of diabetic Akita mice induced liver steatosis without, however, progression to more advanced stages of liver disease.     

The Effect of Perinatal Exposure to Tetrachlorodibenzo-p-Dioxin on the Immune Response of Young Mice

ABSTRACT

The immunocompetence of 5 week old offspring from mice fed control chow or chow containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was evaluated. The 5 ppb maternal feeding level was the only level that produced symptoms of intoxication in the offspring (i.e., facial alopecia and periorbital edema). Mice from mothers fed either 2.5 or 5 ppb of TCDD demonstrated thymus cortex atrophy and a significantly reduced spleen anti-SRBC plaque forming cell (PFC) response, but had normal serum anti-SRBC antibody levels following primary and secondary immunization. Contact sensitivity response to DNFB was significantly reduced only in offspring from mothers fed 5 ppb of TCDD. The blastogenio response of splenic T- and B-lymphocytes to concanavalin-A and E. coli lipopolysaccharide was unaffected by perinatal TCDD exposure. This correlated with the normal appearance of the T- and B-cell dependent areas of the spleens from these animals. There was no significant difference in the differential white blood cell counts between control and TCDD-exposed offspring. Offspring from mothers fed up to 5 ppb of TCDD withstood a live Listeria challenge as well as controls. However, maternal feeding levels as low as 1 ppb of TCDD rendered offspring more sensitive to an endotoxin challenge.     

益可颗粒对正常及糖尿病模型小鼠的降糖作用研究

目的:观察益可颗粒对正常和实验性高血糖小鼠血糖水平的影响。方法:正常小鼠连续灌胃给药15d后,利用血糖试纸检测不同剂量益可颗粒对正常小鼠血糖影响;腹腔注射四氧嘧啶制备糖尿病小鼠模型,实验随机分为7组,每组10只小鼠,即正常对照组、模型对照组,阳性对照组、联合用药组、益可颗粒高剂量组(6.0g/kg)、益可颗粒中剂量组(3.0g/kg)及益可颗粒低剂量组(1.0g/kg),连续灌胃30d后,以血搪试纸测定小鼠空腹血糖。结果:三个剂量的益可颗粒连续灌胃给药15天,均不影响正常小鼠的血糖和体重;6.0g/kg益可颗粒组连续灌胃给药30d,可明显降低四氧嘧啶诱发的高血糖小鼠血搪。结论:益可颗粒不降低正常小鼠血糖,可降低实验性糖尿病小鼠的血糖。     

Hematological Responses to Arsine Exposure: Quantitation of Exposure Response in Mice

Hematological Responses to Arsine Exposure: Quantitation ofExposure Response in Mice. PETERSON, D. P., AND BHATTACHARYYA,M. H. (1985) Fundam. Appl. Toxicol. 5, 499–505. Hematologicalresponses of mice to arsine exposures for 1 hr at 5 to 26 partper million volume (ppmv) are described. Exposure concentrationsranged from a no-effect level for the endpoints studied (5 ppmv)to a concentration lethal to all mice in 4 days (26 ppmv). Hematocritvalues at 24 hr after exposure decreased linearly with increasingarsine concentration in the range 5 to 26 ppmv; the hematocritof the 26-ppmv group reached 10.5% at 24 hr, compared to 48.4%for control mice. Hematocrits of mice from all surviving groupswere at or slightly above control values by 11 days after exposure.Changes in numbers of erythrocytes paralleled changes in hematocrit.Significant increases in circulating reticulocytes occurredat 1 and 5 days after exposure; reticulocyte values returnedto control levels by 11 days after exposure. Changes in erythrocyteosmotic fragility were observed in mice exposed to 15 and 26ppmv arsine