Atherosclerosis In Diabetic Rats Research Articles

Effect of piper Crocatum leaves extract on atherosclerosis in diabetic rats

Atherosclerosis is caused by an inflammatory process in the endothelium due to an imbalance between oxidant and antioxidant agents that often occurs in Diabetes mellitus (DM) patients. Antioxidants that function to neutralize superoxide can be used to prevent atherosclerosis in DM. Piper crocatum leaves shows an unknown antioxidant effect on the atherosclerosis process.The aim of this study is to determine the effect Piper crocatum leaves extract on blood MDA levels and the severity of atherosclerosis in diabetic rats. 30 Sprague Dawley rats were randomly divided into 6 groups, namely, HC (nondiabetic), NC (diabetic-no therapy), PC (metformin 45 mg/kg), PC200, PC300, PC400 (Piper crocatum leaves extract 200/300/ 400 mg/kg/day). Termination, blood sampling, and histopathological analysis were performed after 14 days of treatment. MDA was measured using the TBARS method, and read on a 532 nm wavelength UV-vis spectrophotometer. The severity of atherosclerosis of the rat carotid artery was observed from tissue stained with Haematoxylin Eosin staining at 400x microscope magnification. The mean blood MDA levels in the PC200, PC300, PC400 groups were 1.24 ± 0.26, 0.85 ± 0.35, 0.10 and ± 0.02, respectively, and a decrease in MDA levels was found in the PC200, PC300, and PC400 compared to group NC. The study showed a decrease in the severity of atherosclerosis in groups PC200, PC300, PC400 compared to groups NC. Piper crocatum leaves extract had an effect on decreasing MDA levels and severity of atherosclerosis in diabetic rats.

Elevated retinol binding protein 4 levels are associated with atherosclerosis in diabetic rats via JAK2/STAT3 signaling pathway.

BACKGROUNDAtherosclerosis is a major cause of mortality worldwide and is driven by multiple risk factors, including diabetes, which results in an increased atherosclerotic burden, but the precise mechanisms for the occurrence and development of diabetic atherosclerosis have not been fully elucidated.AIMTo summarize the potential role of retinol binding protein 4 (RBP4) in the pathogenesis of diabetic atherosclerosis, particularly in relation to the RBP4-Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway.METHODSMale Wistar rats were randomly divided into three groups, including a control group (NC group), diabetic rat group (DM group), and diabetic atherosclerotic rat group (DA group). The contents of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), fasting insulin (FINS), fasting plasma glucose, and hemoglobin A1c (HbA1c) were measured. Moreover, the adipose and serum levels of RBP4, along with the expression levels of JAK2, phosphorylated JAK2 (p-JAK2), STAT3, phosphorylated STAT3 (p-STAT3), B-cell lymphoma-2 (Bcl-2), and Cyclin D1 in aortic tissues were also measured. Besides, homeostasis model assessment of insulin resistance (HOMA-IR) and atherogenic indexes (AI) were calculated.RESULTSCompared with the NC and DM groups, the levels LDL-c, TG, TC, FINS, HOMA-IR, RBP4, and AI were upregulated, whereas that of HDL-c was downregulated in the DA group (P < 0.05); the mRNA levels of JAK2, STAT3, Cyclin D1, and Bcl-2 in the DA group were significantly increased compared with the NC group and the DM group; P-JAK2, p-JAK2/JAK2 ratio, p-STAT3, p-STAT3/STAT3 ratio, Cyclin D1, and Bcl-2 at protein levels were significantly upregulated in the DA group compared with the NC group and DM group. In addition, as shown by Pearson analysis, serum RBP4 had a positive correlation with TG, TC, LDL-c, FINS, HbA1C, p-JAK2, p-STAT3, Bcl-2, Cyclin D1, AI, and HOMA-IR but a negative correlation with HDL-c. In addition, multivariable logistic regression analysis showed that serum RBP4, p-JAK2, p-STAT3, and LDL-c were predictors of the presence of diabetic atherosclerosis.CONCLUSIONRBP4 could be involved in the initiation or progression of diabetic atherosclerosis by regulating the JAK2/STAT3 signaling pathway.

Arctium lappa L. polysaccharide can regulate lipid metabolism in type 2 diabetic rats through the SREBP-1/SCD-1 axis

In the analysis of risk factors of diabetes mellitus with coronary heart disease, dyslipidemia is the most important. Previous studies have found that Arctium lappa L. polysaccharide (ALP) can regulate lipid metabolism in type 1 diabetic rats, but it has not been studied in type 2 diabetes. In this study, the regulatory effect of ALP on lipid metabolism in type 2 diabetic rats was investigated by constructing a model of type 2 diabetes. The results of blood biochemical analysis showed that ALP effectively reduced the synthesis of triglycerides and cholesterol, and reduced the risk of atherosclerosis in diabetic rats. Histopathological observation (hematoxylin and eosin, Masson, Periodic Acid-Schiff and oil red O staining) showed that it also effectively regulated lipid metabolism in the liver of diabetic rats and inhibited the process of liver fibrosis. Immunohistochemistry and Western blot analysis showed that ALP regulated the expression of sterol regulatory element-binding protein-1 (SREBP-1) and stearoyl-CoA desaturase 1 (SCD-1) in the liver of diabetic rats. In conclusion, the results of this study demonstrate that ALP can effectively regulate lipid metabolism and reduce the risk of atherosclerosis in type 2 diabetic rats through the SREBP-1/SCD-1 axis.

Antiatherogenic Effect of L-Arginine in Streptozotocin-Induced Diabetic Rats

L-Arginine is one of the essential amino acids elaborated in numerous areas of human physiology which produce nitric oxide (NO). Current study was designed to examine the antiatherogenic and anti-diabetic activities of L-arginine in experimental diabetic rats’ model. Fifty rats were divided into; Control group, L-Arginine group, Diabetic group, Treated group and Prophylactic group. Fasting blood samples were collected from all groups for determination of fasting blood glucose, insulin, insulin resistance, atherogenic index (AI), cardiac risk ratio (CRR), atherogenic coefficient(AC), intercellular adhesion molecule-1 (I-CAM-1), tumor necrosis factor alpha (TNF-α), and nitric oxide (NO). The result showed that oral administration of L-arginine induced significant decrease in the plasma level of I-CAM-1, TNF-α, AC, AI,CRR, glucose, and insulin resistance while induced significant increase in NO, and insulin levels in the treated group . In conclusion, L-arginine may be a novel nutrient, which improves the endothelial function and protects against the development of atherosclerosis in diabetic rats.

The effect of alpha-lipoic acid on expression of VCAM-1 in type 2 diabetic rat.

Macrovascular diabetes complications are generally caused by a process called atherosclerosis. Evidences suggest that to initiate atherosclerosis, oxidated low-density lipoprotein (oxLDL) has to promote the expression of adhesion molecule. Several studies have evidenced the relevance of oxidative stress and atherosclerosis. However, the protective effect of alpha-lipoic acid (ALA) at atherosclerosis still needs to be explored. This study is aimed at investigating the concentration of plasma oxLDL and the expression of adhesion molecule of type 2 diabetes mellitus (DM) using rat model. Eighteen male rats were segregated into three groups labeled as control group, DM group and DM+ALA group. Type 2 diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg) followed by nicotinamide (110 mg/kg). ALA was administered at a dose of 60 mg/kg body weight/day throughout the feeding period of 3 weeks. Plasma oxLDL concentration was measured by enzyme-linked immunosorbent assays and expression of vascular cell adhesion molecule-1 (VCAM-1) was measured by immunohistochemistry. Expression of abdominal aortic adhesion molecule was assessed by calculation with Adobe Photoshop CS3. Analysis of variance test was used to compare the concentration of plasma oxLDL and expression of adhesion molecule. A P-value of 0.05 was considered statistically significant. Plasma oxLDL was lower in diabetic rat+ALA compared with the diabetic rat. Percentage of area VCAM-1 in DM+ALA group was lower than DM group. There were no significant differences between groups in intensity of VCAM-1. In conclusion, ALA showed protective effects against early atherosclerosis in diabetic rats.

Activity of serum paraoxonase 1, lipid profile and atherogenic indexes in diabetic induced rats treated with alpha lipoic acid

Background: Paraoxonase 1 (PON1) is an enzyme attached to high density lipoprotein (HDL-C) which has antioxidant and anti-atherogenic activities. Objectives: In this study, we investigated the effects of alpha lipoic acid on PON1 activity, lipid profile and atherogenic index as well as correlation between PON1 activities and HDL-C in diabetic rats. Materials and Methods: Thirty adult male rats were distributed in three experimental groups in this study. Control (group I), diabetic (group II) and diabetic animals treated with alpha lipoic acid (group III) group. Diabetes mellitus was induced in rats in groups II and III by a single dose of alloxan monohydrate (100 mg/kg; subcutaneous) and then treatment was performed with administration of alpha lipoic acid (100 mg/kg intraperitoneally) in group III for 6 weeks. Blood samples were collected from animals to measure the levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL-C), HDL-C, PON1 activity and correlation the between HDL-C and atherogenic index by PON1. Results: Statistical analysis showed that alpha lipoic acid significantly (P<0.05) inhibited the increase of TG, TC, LDL-C, VLDL, atherogenic index, atherogenic coefficient (AC), and cardiac risk ratio (CRR) when compared to diabetic rats in group II. HDL-C level was increased by alpha lipoic acid. The activity of PON1 was significantly (P<0.05) decreased in diabetic rats and treatment with alpha lipoic acid increased the PON1 activity. Moreover, the activity of PON1 correlated positively with HDL-C and negatively with AC, CRP 1 and CRP2. Conclusions: This study demonstrated that the administration of alpha lipoic acid can improve PON1 activity, lipid metabolism, atherogenic index and is able to reduce the risk of coronary artery diseases and atherosclerosis in diabetic rats.

Effect of alpha-lipoic acid on antioxidant gene expression and kidney injury in alloxan-induced diabetic rats

Background: Myeloperoxidase (MPO) is involved in the initiation, progression, and complications of atherosclerosis in diabetic patients. Objectives: In the current study, the impact of alpha-lipoic acid (LA), a natural antioxidant and a cofactor in the enzyme complexes on MPO, catalase (CAT) and glutathione peroxidase (GPx) activity, glutathione (GSH) and malondialdehyde (MDA) level, histopathology of kidney and expression of antioxidant enzymes, superoxide dismutase (SOD), GPx and CAT which are involved in the detoxification of reactive oxygen species (ROS), was evaluated in alloxan-induced diabetic rats. Materials and Methods: In this study, 30 male Rattus norvegicus rats randomly divided into three groups; control (C), non-treated diabetic (NTD), and LA-treated diabetics (LATD) was induced by alloxan monohydrate (100mg/kg; subcutaneous [SC]). Then treatment was performed with alphaLA (100 mg/kg intraperitoneal (i.p) daily to 6 weeks). Blood sample of animals collected to measure levels of MPO, CAT and GPx activity GSH and MDA. Kidney paraffin sections were prepared to estimate histological studies and to measure quantitative gene expression SOD, GPX and CAT in kidney. Results: Induction of diabetes led to a significant increase in MPO and MDA, reduced GSH level and GPx and CAT activities (P &lt; 0.05). However, treatment with alpha-LA led to a significant elevation in GPx, CAT and GSH levels with a reduction in MPO activities and MDA levels (P &lt; 0.05). Furthermore, the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis results showed increased expressions of GPx, CAT and SOD enzyme in the treatment group compared with the diabetic control group. Histopathological lesions such as increased glomerular volume and lymphocyte infiltration were attenuated in the alpha-LA treated group. Conclusions: Our findings indicated that alpha-LA supplementation is effective in preventing complications induced by oxidative stress and atherosclerosis in diabetic rats.

Protective Effect of Cleome Viscosa Extract on Diet Induced Atherosclerosis in Diabetic Rats

Protective Effect of Cleome Viscosa Extract on Diet Induced Atherosclerosis in Diabetic Rats

In Vitro and In Vivo Antioxidant and Anti-Hyperglycemic Activities of Moroccan Oat Cultivars.

Improvement of oat lines via introgression is an important process for food biochemical functionality. This work aims to evaluate the protective effect of phenolic compounds from hybrid Oat line (F11-5) and its parent (Amlal) on hyperglycemia-induced oxidative stress and to establish the possible mechanisms of antidiabetic activity by digestive enzyme inhibition. Eight phenolic acids were quantified in our samples including ferulic, p-hydroxybenzoic, caffeic, salicylic, syringic, sinapic, p-coumaric and chlorogenic acids. The Oat extract (2000 mg/kg) ameliorated the glucose tolerance, decreased Fasting Blood Glucose (FBG) and oxidative stress markers, including Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Glutathione (GSH) and Malondialdehyde (MDA) in rat liver and kidney. Furthermore, Metformin and Oat intake prevented anxiety, hypercholesterolemia and atherosclerosis in diabetic rats. In vivo anti-hyperglycemic effect of Oat extracts has been confirmed by their inhibitory activities on α-amylase (723.91 μg/mL and 1027.14 μg/mL) and α-glucosidase (1548.12 μg/mL & 1803.52 μg/mL) enzymes by mean of a mixed inhibition.

Protective Effect of Cleome Viscosa Extract on Diet Induced Atherosclerosis in Diabetic Rats

Protective Effect of Cleome Viscosa Extract on Diet Induced Atherosclerosis in Diabetic Rats

Subchronic inhalation of particulate matter 10 coal dust induces atherosclerosis in the aorta of diabetic and nondiabetic rats

This study aimed to elucidate whether subchronic inhalation of particulate matter (PM10) coal dust induces atherosclerosis in diabetic rats. A total of 32 male Wistar rats, were randomly divided into eight groups including four nondiabetic groups and four groups of diabetic rats. These rats were exposed to doses of coal dust equal to 0 mg/m3, 6.25 mg/m3, 12.5 mg/m3, or 25 mg/m3 for 1 hour/day for 28 days. Plasma levels of lipid peroxides were determined as thiobarbituric acid reactive substance. The levels of circulating endothelial cells were analyzed histologically. Foam cells formation was analyzed in aorta and tail artery with Oil Red O staining. Analysis of variance test was used to compare all parameters. Nondiabetic rats exposed to coal dust had significantly increased oxidative stress compared to the control group (p < 0.05). Diabetic rats exposed to coal dust at dose of 25 mg/m3 had significantly increased oxidative stress compared to that of control diabetic rats (p < 0.05). The levels of endothelial damage were significantly increased in diabetic rats exposed to coal dust at doses of 6.25 mg/m3 and 12.5 mg/m3 (p < 0.05) compared to control diabetic rats. The foam cell counts were significantly increased in the aorta of nondiabetic rats exposed to coal dust at doses of 6.25 mg/m3 and 25 mg/m3 compared to control rats (p < 0.05), also in the tail artery at dose of 25 mg/m3. The foam cell counts were significantly increased in the aorta of diabetic rats exposed to coal dust at doses of 6.25 mg/m3 and 12.5 mg/m3 than that in control diabetic rats (p < 0.05). Subchronic inhalation of PM10 coal dust induces atherosclerosis through oxidative stress and endothelial damage in aorta of nondiabetic and diabetic rats.

Inhibition of ceramide synthesis reverses endothelial dysfunction and atherosclerosis in streptozotocin-induced diabetic rats

ObjectivesTo explore the effect of myriocin on EDVD and atherosclerosis in diabetic rats. MethodsRats were fed with a high-fat/high-sucrose/high-cholesterol diet (20% sucrose, 10% animal oil, 1.0% bile salt and 2.5% cholesterol) (hereinafter defined as diabetic groups) or Purina Rodent Chow (NC group), the former was intervened with low dose streptozotocin (30mg/kg) after feeding 1 month to make diabetic model. The NC group was intervened with citrate buffer and the diabetic rats were intervened with myriocin (0.3mg/kg Qod) (MTD group) or just solvent (DC group) for 14 weeks. The EDVD, thickness of fatty deposition under endothelium, ceramide, PI3K/PKB/eNOS, NO and other vital parameters were measured after the rats sacrificed. ResultsIn DC group, the ceramide contents in serum and aorta increased, the EDVD was impaired, the fatty deposition under endothelium increased, and the phosphorylation of PI3K/PKB/eNOS and NO release decreased all compared with the NC group (P<0.05). Compared with the DC group, the ceramide contents in MTD group decreased, the EDVD ameliorated, the fatty deposition diminished, and PI3K/PKB/eNOS phosphorylation and NO release (P<0.05) increased. ConclusionsAfter treated with myriocin, the EDVD in diabetic rats has been improved by increasing PI3K/PKB/eNOS phosphorylation and NO release, and meanwhile the atherosclerosis has reversed.

EFFECT OF FERMENTED CHUB MACKEREL EXTRACT ON LIPID METABOLISM OF DIABETIC RATS

The present study was conducted to evaluate the effect of fermented chub mackerel extract(FCME) on lipid metabolism in diabetic rats. Four week-old male Wistar rats were divided into threegroups based on weight. All rats were induced with diabetes mellitus by single intraperitoneal injectionof streptozotocin at 45 mg/kg body weight. Thereafter, they were randomly distributed to threetreatments with 7 rats assigned to each treatment. One group was the control with no additive, and twotreatmentgroups were given the purified diets supplemented with 1% or 2% FCME. Experimentalresults showed that in comparison to the control, diabetic rats fed FCME increased feed intake (P<0.01)and body weight gain (P<0.05). FCME inclusion significantly reduced the activities of acetyl-CoAcarboxylase (P<0.01) and fatty acid synthetase (P<0.05) in diabetic rats. FCME significantly increasedcholesterol 7 -hydroxylase with no effect on HMG-CoA reductase activity. FCME had no effect onhepatic triglyceride, free cholesterol and phospholipid. FCME inclusion at 1% level significantlyreduced serum triglyceride. FCME significantly increased HDL-cholesterol (P<0.05) with no effect onLDL + VLDL-cholesterol, and significantly reduced atherogenic index. FCME did not significantlyaffect serum insulin and glucose concentration. In conclusion, FCME supplementation altered lipidmetabolism in diabetic rats. FCME supplementation reduced the risk of atherosclerosis in diabetic rats.

The effect of simvastatin on the serum monocyte chemoattractant protein-1 and intracellular adhesion molecule-1 levels in diabetic rats

Objective This study aimed to observe the effect of simvastatin on the serum monocyte chemoattractant protein-1 (MCP-1) and intracellular adhesion molecule-1 (ICAM-1) levels and to probe its protective mechanisms on macroangiopathy in diabetic rats. Methods Twenty-four Wistar rats were randomly assigned to a normal control group (Group A, n=8), and STZ-induced diabetic group (Group B, n=8), or a simvastatin-treated diabetic group (Group C, n=8). Rats in Group C were treated with simvastatin (20 mg kg −1 day −1) 1 week after the establishment of the diabetic model. Groups A and B were treated with corresponding sodium chloride. Peripheral blood glucose was tested weekly; serum MCP-1, ICAM-1, and HbA1c levels were tested at the eighth week. Results At the second, fourth, and eighth week, peripheral blood glucose levels in Group B were similar to those of Group C, which were much higher than those of Group A. Serum MCP-1 and ICAM-1 levels in Groups B and C were higher than those of Group A ( P<.01), and serum MCP-1 and ICAM-1 levels in Group C were lower than those of Group B ( P<.01); HbA1c was not significantly different between Group C and Group B. Conclusion Simvastatin has the effect of anti-inflammation, which may play some protection against the progress of atherosclerosis in diabetic rats.