Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation

In vivo effects of histidine and carnosine against diabetic deterioration in diabetic Balb/cA mice were studied. Histidine and carnosine at 0.5, 1 g/l were added into drinking water. After 4 weeks intake of these agents, the content of histidine and carnosine in plasma, heart and liver significantly elevated (P < 0.05). The intake of these agents significantly decreased plasma glucose and fibronectin levels (P < 0.05); however, only 1 g/l histidine and carnosine treatments significantly increased insulin level (P < 0.05) in diabetic mice. Triglyceride level in heart and liver was dose-dependently reduced by histidine or carnosine treatments (P < 0.05); however, only 1 g/l histidine and carnosine treatments significantly reduced cholesterol level in heart and liver (P < 0.05). The administration of histidine or carnosine significantly enhanced catalase activity and decreased lipid oxidation levels in kidney and liver (P < 0.05); however, only 1 g/l histidine and carnosine treatments significantly increased glutathione peroxidase activity (P < 0.05). The increased interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in diabetic mice were significantly suppressed by the intake of histidine or carnosine (P < 0.05). In human low density lipoprotein, histidine or carnosine showed dose-dependently suppressive effect in glucose-induced oxidation and glycation (P < 0.05). These data suggest that histidine and carnosine are potential multiple-protective agents for diabetic complications prevention or therapy.     

Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin-induced diabetic wistar rats

Flavonoids are non-nutritive dietary components that are widely distributed in plants. The present study investigated the antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid in normal and streptozotocin-induced diabetic Wistar rats. Diabetes as induced in rats by an intraperitoneal injection of streptozotocin. Rutin was orally administered to normal and diabetic rats for a period of 45 days. Fasting plasma glucose, glycosylated haemoglobin, thiobarbituric acid reactive substances and lipid hydroperoxides were significantly (P<0.05) increased, whereas insulin, C-peptide, total haemoglobin, protein levels, non-enzymic antioxidants (glutathione, vitamin C, vitamin E and ceruloplasmin) were decreased significantly (P<0.05) in diabetic rats. Oral administration of rutin to diabetic rats significantly (P<0.05) decreased fasting plasma glucose, glycosylated haemoglobin and increased insulin, C-peptide, haemoglobin and protein levels. Administration of rutin also decreased thiobarbituric acid reactive substances and lipid hydroperoxides and increased the non-enzymic antioxidants significantly (P<0.05). Treatment of normal rats with rutin did not significantly (P<0.05) alter any of the parameters studied. These results show that rutin exhibits antihyperglycaemic and antioxidant activity in streptozotocin-induced diabetic rats.     

Myrtenal alleviates hyperglycaemia,hyperlipidaemia and improves pancreatic insulin level in STZ-induced diabetic rats

Context: Myrtenal is monoterpene a constituent of essential oils found mainly in herbs such as mint, pepper, cumin, etc. It exerts admirable pharmacological activities against many diseases including diabetes. Hyperlipidaemia is a secondary complication of diabetes and also a major risk factor for cardiovascular diseases.

Objective: The present study investigated the possible antihyperlipidaemic efficacy of myrtenal on plasma glucose, pancreatic insulin, plasma and tissue lipid levels in streptozotocin (STZ) induced diabetic rats.

Materials and methods: Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (40?mg/kg b.w.). Myrtenal (80?mg/kg) was administered orally to diabetic rats for a period of 28 d. Plasma glucose, pancreatic insulin, TC, TGs, FFAs, PLs, LDL-C, HDL-C, VLDL, atherogenic index, (HMG-CoA) reductase, LPL, LCAT and liver histology were analyzed.

Results: Diabetic rats showed significantly (p?<?0.05) increased plasma glucose (273.18?mg/dL), total cholesterol (142?mg/dL), triglycerides (126?mg/dL), free fatty acids (118?mg/dL), phospholipids (153?mg/dL), low-density lipoprotein (88.07?mg/dL), very low-density lipoprotein (25.2?mg/dL), atherogenic index, whereas a decrease in the levels of pancreatic insulin (97.48?ng/mg) and high-density lipoprotein (29.12?mg/dL). In addition, the activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase (0.94 HMG-CoA ratio/(mevalonate) increased significantly in contrast to the activities of lipoprotein lipase (4.87 μmoles of glycerol liberated/h/L) and lecithin cholesterol acyltransferase (54.61 μmoles of cholesterol esterified/h/L) in diabetic rats. Treatment with myrtenal significantly (p?<?0.05) improved the levels of plasma glucose, pancreatic insulin and lipid profiles. Moreover, the histopathological analysis of liver was also in agreement with the biochemical findings.

Discussion and conclusions: The present study indicates that myrtenal possess antihyperglycaemic and antihyperlipidemic properties, and could potentially be a useful phytochemical in treating diabetes.     

The hypolipidemic effect of a new ACAT inhibitor, VULM 1457, in diabetic-hypercholesterolaemic rats

The use of inhibitors of enzyme acyl-CoA: cholesterol acyltransferase (ACAT) seems to be a novel potential approach for a therapeutic treatment of dyslipidaemias and atherosclerosis. VULM 1457 is an ACAT inhibitor, which has expressed potent hypolipidemic and antiatherosclerotic effects in previous studies. In this study, we used streptozocin-induced diabetic rats, which were fed a fat-cholesterol diet to evaluate the affect of VULM 1457 on the atherogenic lipids levels in both plasma and liver. VULM 1457, with a slight influence on triglyceride levels, significantly reduced plasma and hepatic cholesterol concentrations (p < 0.05, p < 0.001; respectively) in the diabetic-hypercholesterolaemic rats.     

The influence of rutin on the extracellular matrix in streptozotocin-induced diabetic rat kidney

We previously reported that rutin administration to streptozotocin (STZ)-induced diabetic rats decreased plasma glucose and increased plasma insulin levels. In this study, we have examined the role of rutin on matrix remodelling in the kidney of STZ-induced diabetic rats. STZ was administered intraperitoneally (50 mg kg(-1)) to male albino Wistar rats to induce experimental diabetes. Rutin (100 mg kg(-1)) was orally administered to normal and STZ-induced diabetic rats for a period of 45 days and its influence on the content of hydroxyproline and collagen and on the activity of matrix metalloproteinases (MMPs) were studied. We have also studied the levels of tissue inhibitors of metalloproteinases (TIMPs) in the kidney. STZ-induced diabetic control rats showed increased content of hydroxyproline and collagen, decreased activity of MMPs and increased levels of TIMPs in the kidney. These changes were positively modulated by rutin treatment in STZ-induced diabetic rats, thereby protecting the kidney. In normal rats treated with rutin, none of the parameters studied were significantly altered. From the results obtained, we could conclude that rutin influences MMPs and effectively protects kidney against STZ-induced damage in rats. The effects observed are due to the reduction of plasma glucose levels by rutin.     

Effects of Rutin on Lipid Profile in Hypercholesterolaemic Rats

Abstract: Rutin (3, 3′, 4′, 5, 7‐pentahydrohyflavone‐3‐rhamnoglucoside) is a flavonoid of the flavonol type. Rutin is found in many plants and is also an important dietary constituent of food and plant‐based beverages. Rutin has several pharmacological properties including antioxidant and cardioprotective activities. Also, it was identified that rutin is the major low‐density lipoprotein (LDL) antioxidant compound of mulberry in an in vitro study. The effects of rutin were tested by using it as a supplement in a high‐cholesterol diet. Male rats were fed a high‐cholesterol diet (1 ml/100 g) for 4 weeks with rutin (10 or 100 mg/kg) or rutin 100 mg/kg and lovastatin supplementation to study the hypocholesterolaemic effects of rutin on plasma lipid levels, hepatic enzyme activity, and liver tissue. Feeding the animals a high‐cholesterol diet resulted in marked hypercholesterolaemia and increased the serum level of LDL cholesterol (LDL‐C). Rutin (at 100 mg/kg) alone or in combination with lovastatin significantly reduced the levels of total cholesterol, and LDL‐C and also markedly decreased liver enzymes and weight in animals with a high‐cholesterol diet. Our findings show that 100 mg/kg of rutin alone or with lovastatin supplementation lowered liver weight and enzymes as well as plasma total cholesterol and LDL. The hepatic histopathological results reflect the correlation of rutin and lovastatin combination with both liver weight and the levels of plasma total cholesterol and LDL‐C. These results indicate that rutin in combination with lovastatin has increased anti‐hypercholesterolaemic effects in an animal model.     

Protective effect of Shemamruthaa on lipids anomalies in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinoma-bearing rats

The objective of this work was to evaluate the beneficial effect Shemamruthaa (a siddha formulation which constitutes Hibiscus rosa sinensis, Emblica officinalis, and Honey in define ratio) on lipid metabolism in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinoma-bearing rats. Lipid profile and lipid-metabolizing enzyme were investigated in serum, liver, and kidney of DMBA-induced mammary carcinoma-bearing SD rats. The levels of total cholesterol, free cholesterol, phospholipids, triglycerides, and free fatty acids were significantly increased, whereas, the levels of ester cholesterol were significantly decreased in plasma, liver and kidney of cancer-bearing animals, and those levels were restored to near normal levels upon treatment with SM. Moreover, the activities of total lipase, cholesterol ester synthase, and cholesterol ester hydrolase were found to be increased, and lipoprotein lipase and lecithin cholesterol acyl transferase were decreased in cancer-bearing animals. In addition, the levels of very low-density lipoprotein and low-density lipoprotein were increased, and the level of high-density lipoprotein was decreased. These alterations were recouped back upon treatment with SM when compared to cancer animals. The result indicated that Shemamruthaa administration plays a beneficial role in regulating lipid profile and lipid-metabolizing enzymes in cancer-suffering animals.     

Effect of an aqueous extract of Scoparia dulcis on plasma and tissue glycoproteins in streptozotocin induced diabetic rats

The influence of Scoparia dulcis, a traditionally used plant for the treatment of diabetes mellitus, was examined in streptozotocin diabetic rats on dearrangement in glycoprotein levels. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin. An aqueous extract of Scoparia dulcis plant was administered orally for 6 weeks. The effect of the Scoparia dulcis extract on blood glucose, plasma insulin, plasma and tissue glycoproteins studied was in comparison to glibenclamide. The levels of blood glucose and plasma glycoproteins were increased significantly whereas the level of plasma insulin was significantly decreased in diabetic rats. There was a significant decrease in the level of sialic acid and elevated levels of hexose, hexosamine and fucose in the liver and kidney of streptozotocin diabetic rats. Oral administration of Scoparia dulcis plant extract (SPEt) to diabetic rats led to decreased levels of blood glucose and plasma glycoproteins. The levels of plasma insulin and tissue sialic acid were increased whereas the levels of tissue hexose, hexosamine and fucose were near normal. The present study indicates that Scoparia dulcis possesses a significant beneficial effect on glycoproteins in addition to its antidiabetic effect.     

两色金鸡菊醇提物对实验性糖尿病大鼠血糖血脂的影响

目的：考察两色金鸡菊醇提物对实验性糖尿病大鼠血糖血脂的作用。方法：雄性SD大鼠喂养高糖高脂饲料6周后腹腔注射链脲佐菌素（STZ,30 mg·kg^-1）溶液建立实验性糖尿病大鼠模型。将成模大鼠按血糖均衡随机分为模型组、两色金鸡菊醇提物低（0.4 g·kg^-1）、中（0.8 g·kg^-1）、高（1.6 g·kg^-1）剂量组和二甲双胍（0.2 g·kg^-1）组,取同批次健康大鼠作为正常对照组。每天灌胃给药1次。连续给药4周后检测各组大鼠血中糖化血红蛋白（HbAlc）、血清胰岛素（Ins）含量;检测各组大鼠血清中AST、ALT和血脂四项的含量;计算胰岛素抵抗指数（IRI）、胰岛素敏感指数（ISI）和肝脏指数,将空腹血糖（FBG）绘制成曲线,计算AUC值。结果：干预4周后,与模型组相比,两色金鸡菊醇提物中、高剂量组可降低FBG-AUC（P〈0.05）。两色金鸡菊醇提物三个剂量组可明显降低糖尿病大鼠HbAlc、Ins含量（P〈0.01）;显著降低AST、ALT、TC、TG和LDL-C含量（P〈0.01）,同时增加HDL-C水平（P〈0.01）;显著降低IRI和肝脏指数（P〈0.01）,增加ISI（P〈0.05）。结论：两色金鸡菊醇提物具有改善糖尿病大鼠血糖血脂紊乱的作用。     

The thienotriazolodiazepine Ro 11-1464 increases plasma apoA-I and promotes reverse cholesterol transport in human apoA-I transgenic mice

BACKGROUND AND PURPOSE

Ro 11-1464 is a thienotriazolodiazepine previously described to selectively stimulate apolipoprotein A-I (apoA-I) production and mRNA level in human liver cells. Here, we studied its effects upon oral administration to human apoA-I transgenic (hapoA-I) mice.

EXPERIMENTAL APPROACH

HapoA-I mice were treated for 5 days with increasing doses of Ro 11-1464. Macrophage reverse cholesterol transport (mph-RCT) was assessed by following [³H]-cholesterol mobilization from pre-labelled i.p. injected J774 macrophages to plasma, liver and faeces. Effects on plasma lipids, apoproteins, lecithin-cholesterol : acyltransferase (LCAT) and liver enzymes, as well as on faecal excretion of cholesterol and bile salts, and on liver lipids and mRNA contents were determined.

KEY RESULTS

Treatment with Ro 11-1464 300 mg·kg⁻¹·day⁻¹ resulted in a nearly 2-fold increase in plasma apoA-I, a 2- to 3-fold increase in the level of large sized-pre-β high-density lipoprotein and a 3-fold selective up-regulation of hepatic apoA-I mRNA, but a marked decrease in all plasma lipids and LCAT activity. Mpm-RCT was decreased in blood but markedly increased in faecal sterols (4-fold) and bile acids (1.7-fold). However, liver weight and liver enzymes in plasma were also increased, in parallel with an increase in liver cholesterol ester content (all these effect being significant).

CONCLUSION AND IMPLICATIONS

In this model Ro 11-1464 causes increased hepatic expression and plasma levels of apoA-I and a suppression of LCAT, and a marked enhancement of reverse cholesterol transport, but also some symptoms of liver toxicity. The compound may therefore be a prototype for a next generation of anti-atherosclerotic medicines.     

Effect of veratric acid on the cardiovascular risk of L-NAME-induced hypertensive rats

Hypertension is associated with dyslipidemia, which is a significant risk factor for cardiovascular complications. This study was undertaken to investigate the effects of veratric acid (VA) on blood pressure, plasma, and tissue lipid profile in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Hypertension was induced in adult male albino rats of Wistar strain, weighing 180-220 g, by oral administration of L-NAME (40 mg/kg) in drinking water for 4 weeks. Rats were treated with VA (40 mg/kg) for 4 weeks. L-NAME-treated rats showed significant increase in mean arterial pressure and heart rate. A significant increase in the concentrations of plasma, tissue (liver and kidney) lipids, and lipoproteins and a significant decrease in the concentration of high-density lipoprotein cholesterol were noticed in L-NAME-induced hypertensive rats. The activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase increased significantly in the liver and kidney, whereas the activities of lipoprotein lipase and lecithin cholesterol acyl transferase were decreased significantly in the plasma of hypertensive rats. Histopathology of liver and kidney and in vitro study also confirmed the biochemical findings of this study. Thus, oral administration of VA reduced hyperlipidemia related to the risk of hypertension.     

Effect of reserpine treatment on low-density lipoproteins in arterial wall and internal organs of rats

The effects were determined in rats of single injections of reserpine at increasing doses (0.5, 1.58, and 5.0 mg/kg) on low-density lipoprotein (LDL) and cholesterol in aortic wall, heart, liver, kidney, and adrenal gland. Catecholamine levels in plasma, heart, and liver, arterial blood pressure, and heart rate were also monitored. Reserpine was injected intraperitoneally, followed immediately by the administration of [3H]cholesterol by gavage. Twelve hours later, homologous 125I-tyramine cellobiose-labeled LDL (125I-TC-LDL) was injected intravenously. Twenty-four hours later, the rats were killed, and the radioactivities of aortic walls, heart, liver, kidney, and adrenal glands were determined. The results showed that after reserpine treatment the accumulation of both the 125I-TC label derived from LDL and total [3H]cholesterol was significantly reduced in aortic wall and heart, increased in liver, and unchanged in the kidney and adrenal gland. At higher doses (1.58 and 5.0 mg/kg), reserpine significantly accelerated the plasma clearance of radiolabelled LDL. Plasma noradrenaline in reserpine-treated animals decreased maximally (86%) by 12 h and by 61-71% at 36 h compared with the control. Plasma adrenaline increased transiently after injection of reserpine and then returned to the basal levels. Reserpine greatly decreased noradrenaline and adrenaline levels in heart and liver. Arterial blood pressure was decreased significantly (0.001 < p < 0.05) at 12 h by the two lower doses of reserpine and then returned to normal values over the next 24 h. The results indicate that reserpine decreases LDL cholesterol in artery wall and heart and increases it in liver. These findings suggest that reserpine could find a new use as a cholesterol-lowering drug for the prevention of atherosclerosis.     

Effects of gemfibrozil treatment on vascular reactivity of streptozotocin-diabetic rat aorta

The effects of gemfibrozil treatment on plasma lipids, lipid peroxides and vascular reactivity of aorta were investigated in diabetic rats. Rats were divided randomly into two groups: control and diabetic. Diabetes was induced by a single intraperitoneal injection of streptozotocin (45 mg kg(-1)). Twelve weeks after the induction of diabetes, some of the control and diabetic rats were started treatment with gemfibrozil (100 mg kg(-1) daily; gavage) for 2 weeks. Blood glucose, plasma triglyceride, cholesterol, low-density lipoprotein (LDL) cholesterol and thiobarbituric acid reactive substances (TBARS) levels were markedly increased and gemfibrozil treatment restored these parameters in diabetic rats. However high-density lipoprotein (HDL) cholesterol levels did not differ in all experimental groups. In diabetic rats, the endothelium-dependent relaxations to acetylcholine were decreased when compared with control rats. Gemfibrozil treatment restored the endothelium-dependent responses to acetylcholine in diabetic rats. The endothelium-independent relaxation responses to sodium nitroprusside were not altered in all groups. These findings suggest that gemfibrozil treatment has beneficial effects against cardiovascular and metabolic complications of diabetes via its hypolipidaemic and antioxidant properties.     

某些药物对大鼠血浆和肝脏脂蛋白脂酶活性及血浆胆固醇的影响

Lipoprotein lipase (LPL) is one of the most important factors in lipoprotein metabolism. The plasma and liver LPL activities (indicaded by fatty acid release), the ratio of LPL activity to total lipase activity and theoplasma cholesterol levels in rats treated with drugs were determined so as to study the relationship between LPL and lipoprotein metabolism.Plasma LPL activity is negatively related to the total cholesterol and high density lipoprotein cholesterol levels. As the liver LPL activity, increased, the plasma LPL activity also increased. When rats were treated with insulin, phenytoin or Radix Polygonum multiflorum, the plasma and liver LPL activities and the ratio of LPL activity to total lipase activity increased, whereas the plasma total cholesterol and high density lipoprotein cholesterol levels decreased. No significant effect of phenytoin on the total cholesterol level was observed, When large doses of phenytoin were used, the plasma very low density lipoprotein and low density lipoprotein cholesterol level increased and the ratio of high density lipoprotein cholesterol to total cholesterol decreased.     

Antihyperglycaemic and anti-oxidant properties of Andrographis paniculata in normal and diabetic rats

1. Oxidative stress is believed to be a pathogenetic factor in the development of diabetic complications. In the present study, we investigated the ethanolic extract of the aerial parts of Andrographis paniculata for antihyperglycaemic and anti-oxidant effects in normal and streptozotocin-induced type I diabetic rats. 2. Normal and diabetic rats were randomly divided into groups and treated orally by gavage with vehicle (distilled water), metformin (500 mg/kg bodyweight) or the extract (400 mg/kg bodyweight), twice a day for 14 days. 3. At the end of the 14 day period, the extract, like metformin, significantly increased bodyweight (P < 0.01) and reduced fasting serum glucose in diabetic rats (P < 0.001) when compared with vehicle, but had no effect on bodyweight and serum glucose in normal rats. Levels of liver and kidney thiobarbituric acid-reactive substances (TBARS) were significantly increased (P < 0.0001, P < 0.01, respectively), while liver glutathione (GSH) concentrations were significantly decreased (P < 0.005) in vehicle-treated diabetic rats. Liver and kidney TBARS levels were significantly lower (P < 0.0001, P < 0.005, respectively), whereas liver GSH concentrations were significantly higher (P < 0.05) in extract- and metformin-treated diabetic rats compared with vehicle-treated diabetic rats. Andrographis paniculata significantly decreased kidney TBARS level (P < 0.005) in normal rats. Hepatic superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were significantly lower in vehicle-treated diabetic rats compared with vehicle-treated normal rats. The extract, as well as metformin, significantly increased the activity of SOD and CAT, but had no significant effect on GSH-Px activity in diabetic rats. The extract and metformin did not produce significant changes in the activity of these anti-oxidant enzymes in normal rats. 4. Our results show that oxidative stress is evident in streptozotocin-diabetic rats and indicate that the ethanolic extract of A. paniculata not only possesses an antihyperglycaemic property, but may also reduce oxidative stress in diabetic rats.     

荜茇宁衍生物对高脂血症大鼠调脂作用及其机制的研究

目的：探讨荜茇宁（GBN）的衍生物（GBNT）对高脂血症大鼠的调脂作用,并考察其作用机制。方法高脂饲料喂养Wister 大鼠,建立高脂血症模型,造模同时连续灌胃给药8周后,腹主动脉取血,检测各组大鼠血清中总胆固醇（TC）,甘油三酯（TG）,低密度脂蛋白胆固醇（LDL-C）,高密度脂蛋白胆固醇（HDL-C）含量;HE 染色检测肝脏病理学形态;Western blot 方法研究低密度脂蛋白受体（LDLR）,卵磷脂胆固醇脂酰基转移酶（LCAT）,胆固醇7α-羟化酶（CYP7A）蛋白表达的变化。结果GBNT 低、高剂量组均能降低模型大鼠 TC、TG 和 LDL-C 的含量,升高 HDL-C 含量;上调 LDLR,LCAT,CYP7A1蛋白的表达;并减轻肝脏脂肪变性。结论GBNT 具有降低高脂血症模型大鼠血脂水平的作用,其机制可能与调节 LCAT,CYP7A1等脂质代谢酶表达有关。     

Anti-hyperlipidemic activity of spider brake (Pteris multifida) with rats fed a high cholesterol diet

This study evaluates the possible potency of the anti-hyperlipidemic effect of spider brake [(Pteris multifida Poiret (Pteridaceae)]. We investigated this by feeding the hyperlipidemic Sprague-Dawley rats, caused by a high cholesterol diet, with lyophilized powder of spider brake (LSB) and compared the result with the rats fed with β-sitosterol. The results indicated that the administration of lyophilized powder of spider brake (LSB) lowered the hyperlipidemic level on rats. The relative weights of the liver, adipose tissue, and relative adipose tissue of 10% substitutions of LSB group (LSB-10) showed a significant decrease (P?<?0.05) by 6%, 15.9%, and 14.3% in contrast to the untreated counterparts (control), respectively. A significantly lower (P?<?0.05) plasma TG, low density lipoprotein cholesterol, low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio, liver CH, and TG contents were also observed in LSB-10 compared to the untreated counterparts (by 36.8%, 21%, 18.7%, 10.2% and 14.3% reduction, respectively). Simultaneously, the wet fecal weight, dry fecal weight, nitrogen compounds, excretion of neutral steroids, and bile acids significantly (P?<?0.05) increased by 9.6%, 10.6%, 23.7%, 9.7%, and 3.4% respectively. The results showed that LSB could cause not only a reduction in CH and TG, but also could increase the excretion of lipids and metabolic by-products via the intestinal tract.     

Relationship among cholesterol, superoxide anion and endothelium-dependent relaxation in diabetic rats

The purpose of the present study was to investigate the time course of changes in plasma low-density lipoprotein (LDL) cholesterol, tissue lipid peroxidation, the expression of hepatic LDL-receptor mRNA and aortic superoxide dismutase, and the relaxation response to acetylcholine in streptozotocin-induced diabetic rats. Plasma cholesterol and LDL levels were significantly increased in both 4- and 10-week diabetic rats. The tissue malonic dialdehyde content in aortas was increased in 10-week compared to 1- or 4-week diabetic rats. The expression of mRNA for LDL receptor mRNA in the liver showed a decrease in both 4- and 10-week diabetic rats. Hepatic LDL-receptor binding activity decreased significantly in 10-week diabetic rats, and decreased binding activity in diabetic rats was improved by the chronic administration of cholestyramine. The relaxation responses to acetylcholine in helical strips of the aorta precontracted with noradrenaline were significantly decreased in 10-week, but not in 1- or 4-week streptozotocin-induced diabetic rats. The decreased relaxation response to acetylcholine was improved by chronic cholestyramine. Both the expression of Mn-superoxide dismutase mRNA and the activity of superoxide dismutase in the aorta were decreased in 10-week, but not in 4-week diabetic rats. From time-course studies, our data suggest that not only increased LDL cholesterol but also decreased activity of superoxide dismutase are responsible for the decreased relaxation response induced by acetylcholine.     

Protective effect of herbomineral formulation (Dolabi) on early diabetic nephropathy in streptozotocin-induced diabetic rats

The effect of a herbomineral formulation (HMF) on early diabetic nephropathy was investigated. Diabetes was induced in Wistar rats by administering streptozotocin (55 mg/kg, intraperitoneally). The occurrence of early diabetic nephropathy in rats was revealed by high plasma glucose and depleted liver glycogen, decreased glucose uptake by peripheral tissue, impaired renal function, increased antioxidants and lipid peroxidation in kidney. These changes were accompanied by elevated malondialdehyde, glutathione and superoxide dismutase activity in kidney. Furthermore, increased total urine volume, urinary albumin excretion rate, urinary albumin to creatinine ratio, increased relative kidney weight, decreased glomerular filtration rate (GFR) and urinary creatinine were also observed in diabetic nephropathy rats. HMF treatment significantly lowered blood glucose, glycosylated hemoglobin, creatinine, blood urea nitrogen, triglycerides, total cholesterol, serum albumin level, total urine volume, urinary albumin excretion rate, urinary albumin to creatinine ratio and relative kidney weight, and increased urinary creatinine and GFR. Altered levels of antioxidants, viz. lipid peroxidation, glutathione and superoxide dismutase (SOD), in kidney of diabetic nephropathy rats were restored. Histopathological findings indicated dense mesangial matrix in the glomeruli of diabetic nephropathy rats, which may be due to over-activation of matrix metalloproteinases and was reduced following HMF treatment. Our experimental findings clearly demonstrate that HMF has an ability to prevent the progression of early diabetic nephropathy. Such protective effect of HMF might be due to the presence of flavonoids (catechin, quercetin, rutin) and triterpene saponins (oleanolic acid and gymnemic acid) which are known to possess potent antioxidant properties.     

Streptozotocin-induced diabetes in rat. II. Lipid and lipid peroxide changes of lipoprotein fractions in diabetes complicated by hypertension and myocardial infarction

Lipid peroxide levels and plasma lipids were studied in plasma lipoprotein fractions of streptozotocin diabetic rats, spontaneous hypertensive rats (SHR) + diabetes, and in myocardial infarction rats (MIR) + diabetes. The duration of diabetes in all experimental groups was 2.5 months. We found a tendency of elevation of cholesterol in VLDL and fall in HDL2 but the differences were not significant. Total plasma triglycerides were increased in the three diabetic groups, and the increase was due to LDL fraction but again the differences were not significant. The lipid peroxide (LP) level in total plasma showed a significant increase in the three diabetic groups: in Wistar diabetic rats LP increased 3 times, in MIR + diabetes 3.5 times, and in SHR + diabetes 5 times. The increase of LP in the three diabetic groups was due to LDL with good correlation (r = 0.60) between LP and triglycerides in LDL of the three diabetic groups. The results are in agreement with the concept of the importance of lipoprotein fraction changes: increased cholesterol, triglycerides and lipid peroxides in atherogenic (VLDL and LDL) fractions, and decreased levels in antiatherogenic (HDL, HDL2) fractions in diabetes mellitus.