Vulnerability of Gastric Mucosa in Diabetic Rats,Its Pathogenesis and Amelioration by Cuminum cyminum

Various studies have indicated that peptic ulcers occurring during the course of diabetic state are more severe and often associated with complications such as gastrointestinal bleeding. This study is the first attempt to understand the pathogenesis of gastric ulcers occurring during the diabetic state considering alternate biochemical pathways using suitable markers and its amelioration by Cuminum cyminum. In this study, diabetic rats showed a progressive increase in the stomach advanced glycated end products formation, gastric mucosal tumour necrosis factor-α and Thiobarbituric acid reactive substances levels as compared to normal control (nondiabetic) rats. There was decrease in gastric mucosal content, antioxidant enzymes and cellular ATPase enzyme levels of diabetic gastric mucosa when compared to the normal control group. mRNA expression of epidermal growth factor was found to be significantly higher as compared to normal control animals. Further methanol extract of Cuminum cyminum treatment to diabetic animals caused a reduction in blood glucose, and ulcer score when compared to diabetic control rats. It significantly increased gastric mucus content, antioxidant status and cellular ATPase enzyme levels as compared to diabetic control animals. Methanol extract of Cuminum cyminum inhibited advanced glycated end products formation in vitro as well as in vivo.     

Beneficial effect of Azadirachta indica on advanced glycation end-product in streptozotocin-diabetic rat

Context: Both oxidation and hyperglycemia cause increased glycation and the formation of advanced glycation end-products (AGEs) which underlie the complications of diabetes.

Objective: The goal of this article is to determine the effect of the chloroform extract from leaves of Azadirachta indica A. Juss; (Meliaceae) (AI) on the formation of glycated protein.

Materials and methods: Chloroform extract was subjected to in vitro bioassays to evaluate advanced glycation end-products formation. Bovine serum albumin (BSA)-glucose, BSA-methylglyoxal, Amadori-rich protein, glycated hemoglobin, oxidation, and glycation of LDL were determined. Doses of AI of 200?mg/kg/d by oral gavage were administered once daily for 30?d, at streptozotocin-induced diabetic rats. After this period, renal damage (TBARS), glucose, methylglyoxal, glycolaldehyde, and tail tendon collagen were investigated.

Results and discussion: AI exhibits protective action in BSA against glycation formation, GHb, protein levels, and LDL against glycation and oxidation. The renal glucose level decreases a 3.9?mg/g wet tissue. TBA-reactive substance showed a significant decrease to 1.82?mmol/mg protein. In addition, AI showed inhibitory activity against AGEs formation, methylglyoxal, and glycolaldehyde levels in kidney. Treatment with AI in rat tail tendon produced a reduction in cross-linking of collagen proteins. The antiglycation activities of A. indica were attributed in part to their antioxidant activity. AI alleviated oxidative stress under diabetic conditions through the inhibition of lipid peroxidation prevents the onset renal damage.

Conclusion: We found that A. indica is an inhibitor AGE formation, and oxidative stress with a renoprotective effect, which are considered to play important roles in diabetic kidney disease.     

Effects of a new advanced glycation inhibitor,LR-90, on mitigating arterial stiffening and improving arterial elasticity and compliance in a diabetic rat model: aortic impedance analysis

BACKGROUND AND PURPOSE

We determined the effects of treatment with LR-90, an inhibitor of advanced glycation end products, on the mechanical properties of the arterial system in streptozotocin (STZ)-induced diabetic Sprague Dawley rats, using aortic impedance analysis, and further investigated the effects of LR-90 on the progression of aortic pathology.

EXPERIMENTAL APPROACH

STZ-induced diabetic rats were treated with or without LR-90 (50 mg L^-1 in drinking water) for 8 weeks and compared with control groups. Arterial BP measurements, various metabolic parameters, aortic histopathology, collagen cross-linking, AGE accumulation, and RAGE protein expression in aortic tissue were determined. Pulsatile parameters were evaluated using a standard Fourier series expansion technique and impulse response function of the filtered aortic input impedance spectra.

KEY RESULTS

LR-90 reduced glycated haemoglobin and triglycerides levels, although it had no effect on the glycaemic status. LR-90 did not affect arterial BP, but prevented the diabetes-induced increase in peripheral resistance and variations in aortic distensibility, as it reduced aortic characteristic impedance by 21%. LR-90 also prevented the elevation in wave reflection factor, as indicated by a 22.5% reduction and an associated increase of 23.5% in wave transit time, suggesting it prevents the augmentation of the systolic load of the left ventricle. Moreover, LR-90 inhibited collagen cross-linking and the accumulation of AGE and RAGE in the vasculature of diabetic rats.

CONCLUSIONS AND IMPLICATIONS

Treatment with LR-90 may impart significant protection against diabetes-induced aortic stiffening and cardiac hypertrophy and provides an additional therapeutic option for treatment of AGE associated diabetic complications.     

Green tea attenuates diabetes induced Maillard-type fluorescence and collagen cross-linking in the heart of streptozotocin diabetic rats.

The enhanced myocardial collagen content, collagen glycation and the resulting advanced glycation end products (AGE) which exhibit the characteristics of increased cross-linking are proposed for the stiffness of myocardium in diabetes. To explore the cardioprotective effect of green tea in diabetes, we study the effect of green tea extract on myocardial collagen characteristics in streptozotocin diabetic rats. The effect of green tea on marker enzymes in serum and cardiac tissues were also assayed to understand the extent of protection. Six weeks after the diabetes induction, diabetic rats were treated with green tea extract [300 mg (kg body weight)(-1)day(-1)] for 4 weeks. AGE were determined by fluorescence assay and cross-linking of collagen by solubility measurement while collagen content was measured by biochemical assay. The activities of aspartate transaminase (AST), lactate dehydrogenase (LDH) and creatine kinase (CPK) were measured by biochemical assay. The increase in blood glucose, glycated hemoglobin and systolic blood pressure in diabetic rats were reduced upon green tea treatment. The activities of AST, LDH and CPK were significantly increased in serum whereas decreased in cardiac tissues in diabetic rats representing the cardiac damage. Administration of green tea to diabetic rats significantly ameliorates these enzyme activities. There was no significant difference in the myocardial collagen content among the experimental rats. A significant (P<0.05) increase in collagen linked Maillard-type fluorescence and decrease in collagen solubility in the myocardium of diabetic rats as compared to control rats (0.955+/-0.02 versus 0.683+/-0.04 and 30+/-1.41 versus 45.17+/-1.17, respectively) indicates the increase in advanced glycation end products formation and degree of collagen cross-linking. Green tea administration to diabetic rats significantly (P<0.05) decreased the fluorescence (0.73+/-0.02) whereas increased the solubility of collagen (41.5+/-1.04) indicating the reduction in advanced glycation end products and collagen cross-linking. The present study reveals that green tea by ameliorating myocardial collagen characteristics may provide a therapeutic option in the treatment of cardiovascular complications of diabetes.     

Ameliorative effects of glycyrrhizin on streptozotocin-induced diabetes in rats

Objectives Glycyrrhizin is the main water‐soluble constituent of the root of liquorice (Glycyrrhiza glabra). The study investigates the effect of glycyrrhizin on streptozotocin (STZ)‐induced diabetic changes and associated oxidative stress, including haemoglobin‐induced free iron‐mediated oxidative reactions. Methods Male Wistar rats were grouped as normal control, STZ‐induced diabetic control, normal treated with glycyrrhizin, diabetic treated with glycyrrhizin and diabetic treated with a standard anti‐hyperglycaemic drug, glibenclamide. Different parameters were studied in blood and tissue samples of the rats. Key findings Glycyrrhizin treatment improved significantly the diabetogenic effects of STZ, namely enhanced blood glucose level, glucose intolerant behaviour, decreased serum insulin level including pancreatic islet cell numbers, increased glycohaemoglobin level and enhanced levels of cholesterol and triglyceride. The treatment significantly reduced diabetes‐induced abnormalities of pancreas and kidney tissues. Oxidative stress parameters, namely, serum superoxide dismutase, catalase, malondialdehyde and fructosamine in diabetic rats were reverted to respective normal values after glycyrrhizin administration. Free iron in haemoglobin, iron‐mediated free radical reactions and carbonyl formation in haemoglobin were pronounced in diabetes, and were counteracted by glycyrrhizin. Effects of glycyrrhizin and glibenclamide treatments appeared comparable. Conclusion Glycyrrhizin is quite effective against hyperglycaemia, hyperlipidaemia and associated oxidative stress, and may be a potential therapeutic agent for diabetes treatment.     

Renoprotective effect of aged garlic extract in streptozotocin-induced diabetic rats

Objective:

Aged garlic extract (AGE) has been proven to exhibit antioxidant, hypolipidemic, hypoglycemic and antidiabetic properties. However, its effect on diabetic nephropathy was unexplored. Therefore, the present study was designed to investigate the renoprotective effect of AGE in streptozotocin-induced diabetic rats.

Materials and Methods:

Albino Wistar rats were induced with diabetes by a single intraperitoneal injection of 45 mg/kg b.w. of streptozotocin. Commercially available AGE was supplemented orally at a dose of 500 mg/kg body weight/day. Aminoguanidine, which has been proven to be an anti-glycation agent was used as positive control and was supplemented at a dose of 1 g/L in drinking water. The serum and urinary biochemical parameters were analyzed in all the groups and at the end of 12 weeks follow up, the renal histological examination were performed using H & E and PAS staining.

Results:

The diabetic rats showed a significant change in the urine (P < 0.001) and serum (P < 0.01) constituents such as albumin, creatinine, urea nitrogen and glycated hemoglobin. In addition, the serum lipid profile of the diabetic rats were altered significantly (P < 0.05) compared to that of the control rats. However, the diabetic rats supplemented with aged garlic extract restored all these biochemical changes. The efficacy of the extract was substantiated by the histopathological changes in the kidney.

Conclusion:

From our results, we conclude that aged garlic extract has the ability to ameliorate kidney damage in diabetic rats and the renoprotective effect of AGE may be attributed to its anti-glycation and hypolipidemic activities.KEY WORDS: Aged garlic extract, anti-glycation, diabetes, diabetic nephropathy, hypolipidemic, renoprotective     

Pioglitazone improves left ventricular diastolic function and decreases collagen accumulation in prediabetic stage of a type II diabetic rat.

This study investigated the effect of pioglitazone, an insulin sensitizer, on metabolic abnormalities and oxidative stress as a cause of myocardial collagen accumulation in prediabetic rat hearts. Twenty male diabetic rats and 9 male nondiabetic age-matched rats were used. The diabetic rats were divided into two groups: diabetic treated and untreated. Pioglitazone was mixed in rat chow fed to the diabetic treated group (0.01%). Treatment duration was 5 weeks. At baseline (15 weeks) and 20 weeks of age, blood glucose, lipid, insulin, and plasma malondialdehyde-thiobarbituric acid (MDA) levels were measured and Doppler echocardiography was tracked. At 20 weeks of age, left ventricular collagen content was studied. Blood glucose, plasma insulin, and triglyceride levels in the diabetic treated group were significantly lower than those in the untreated diabetic group. Deceleration time (ms) of early diastolic inflow in the treated diabetic group decreased significantly compared with the untreated diabetic group (65 +/- 8 vs. 77 +/- 8, p < 0.01). Ratio of left ventricular weight to body weight (mg/g) and ratio of left ventricular collagen content to dry weight (mg/100 mg) were decreased in the treated diabetic group (1.5 +/- 0.1, 1.3 +/- 0.3) compared with the untreated diabetic group (1.7 +/- 0.2, p < 0.01; 1.7 +/- 0.3, p < 0.05). Plasma MDA concentration (nmol/ml) significantly decreased (2.9 +/- 0.3 at baseline to 2.3 +/- 0.3 at 20 weeks, p = 0.001) in the treated diabetic group, and was lower than that in the untreated diabetic group (3.2 +/- 0.7 at 20 weeks, p < 0.05). Pioglitazone improved glucose and lipid metabolism and reduced oxidative stress in the left ventricle, which decreased left ventricular collagen accumulation and improved left ventricular diastolic function of prediabetic rat hearts.     

Nephroprotective effect of Paeonia emodi via inhibition of advanced glycation end products and oxidative stress in streptozotocin–nicotinamide induced diabetic nephropathy

The present study aimed to evaluate the effect of alcohol (PA) and hydroalcohol (PHA) extract of Paeonia emodi Royale roots in treatment of streptozotocin–nicotinamide induced diabetic nephropathy. Diabetes mellitus was induced in male Wistar rats by streptozotocin (65 mg/kg intraperitoneally) 15 minutes after nicotinamide (230 mg/kg, intraperitoneally) administration and diabetic nephropathy was assessed by measuring serum glucose, renal parameters (urea, uric acid, creatinine, and blood urea nitrogen level) and lipid profile. The rats were treated with different doses of extracts (100 mg/kg, 200 mg/kg, and 400 mg/kg) for 45 days. Oxidative stress was assessed by measuring tissue antioxidant enzymes level along with the formation of advanced glycation end-products (AGEs) in kidney. PA and PHA (400 mg/kg) produced significant attenuation in the serum glucose level (165.08 ± 3.353 mg/dL and 154.27 ± 2.209 mg/dL, respectively) as compared to control. Elevated renal parameters, lipid levels, tissue antioxidant enzymes and AGE formation were also restored in a dose-dependent manner. These findings suggest that by amelioration of oxidative stress and formation of AGEs, PA and PHA significantly inhibited the progression diabetic nephropathy in rats.     

Nephroprotective effect of Paeonia emodi via inhibition of advanced glycation end products and oxidative stress in streptozotocin–nicotinamide induced diabetic nephropathy

The present study aimed to evaluate the effect of alcohol (PA) and hydroalcohol (PHA) extract of Paeonia emodi Royale roots in treatment of streptozotocin–nicotinamide induced diabetic nephropathy. Diabetes mellitus was induced in male Wistar rats by streptozotocin (65 mg/kg intraperitoneally) 15 minutes after nicotinamide (230 mg/kg, intraperitoneally) administration and diabetic nephropathy was assessed by measuring serum glucose, renal parameters (urea, uric acid, creatinine, and blood urea nitrogen level) and lipid profile. The rats were treated with different doses of extracts (100 mg/kg, 200 mg/kg, and 400 mg/kg) for 45 days. Oxidative stress was assessed by measuring tissue antioxidant enzymes level along with the formation of advanced glycation end-products (AGEs) in kidney. PA and PHA (400 mg/kg) produced significant attenuation in the serum glucose level (165.08 ± 3.353 mg/dL and 154.27 ± 2.209 mg/dL, respectively) as compared to control. Elevated renal parameters, lipid levels, tissue antioxidant enzymes and AGE formation were also restored in a dose-dependent manner. These findings suggest that by amelioration of oxidative stress and formation of AGEs, PA and PHA significantly inhibited the progression diabetic nephropathy in rats.     

Beneficial effects of Momordica charantia seeds in the treatment of STZ-induced diabetes in experimental rats

The aim of the present study was to evaluate the effect of the aqueous extract of seeds of two varieties, namely a country and hybrid variety of Momordica charantia (MCSEt1 and MCSEt2) on oxidative stress in plasma and pancreas of streptozotocin (STZ) induced diabetic rats. Oral administration of each of the seed extracts at a dosage of 150 mg/kg body weight for 30 d resulted in a significant reduction in plasma glucose, thiobarbituric acid-reactive substances, lipid-hydroperoxides, alpha-tocopherol and significant improvement in ascorbic acid, reduced glutathione and insulin. The treatment also resulted in a significant reduction in thiobarbituric acid reactive substances, lipid-hydroperoxides, superoxide dismutase, catalase, glutathione peroxidase and significant improvement in reduced glutathione in pancreas of drug treated diabetic rats when compared to the untreated diabetic rats. On the basis of results obtained, it may be concluded that the treatment of Momordica charantia seed varieties may effectively normalize the impaired oxidative stress in streptozotocin induced-diabetes than the glibenclamide treated groups.     

Effect of Cymbopogon citratus Stapf extract on lipid profile and antioxidant status in streptozotocin-induced diabetic rats

OBJECTIVE To investigate the effects of Cymbopogon citratus Stapf water extract on lipid profile and antioxidant status in streptozotocin-induced diabetic rats.METHODS Diabetes was induced by injection of streptozotocin(STZ,50mg·kg-1)intraperitoneally.Diabetic rats were divided into 5groups,consisting of 6rats.GroupⅠ,reserved as diabetic control,was administered distilled water and groupⅡ,reserved as positive control,was administered glibenclamide(10mg·kg-1·d-1)throughout the duration of the experiment.Those in groupⅢ,ⅣandⅤ were administered 250,500 and 1000mg·kg-1·d-1 of the extract,respectively for 28 d.RESULTS Treatment with 500 and 1000mg·kg-1·d-1 of the extract resulted in reduction of serum AST,ALT,serum cholesterol,triglycerides and LDL,whereas HDL was found to be increased compared with diabetic control rats(P<0.05).Moreover,increased serum activities of superoxide dismutases and catalase were found in diabetic rats treated with the extract whereas serum thiobarbituric acid reactive substance was decreased,in comparison with diabetic control rat(P<0.05).CONCLUSION Cymbopogon citratus Stapf water extract provides a benefit effect on serum lipid and antioxidant effect in diabetic rats.Thus,the extract may lower cardiovascular disease risk and others complications related to hyperlipidemia and oxidative stress in diabetic patients.     

Modulatory effects of Aloe vera leaf gel extract on oxidative stress in rats treated with streptozotocin

Oxidative stress is currently suggested as a mechanism underlying diabetes and diabetic-related complications. Oxidative stress results from an imbalance between radical-generating and radical-scavenging systems. Many secondary plant metabolites have been reported to possess antioxidant activity. This study was designed to evaluate the potential antioxidative activity of the ethanolic extract from Aloe vera leaf gel in the plasma and pancreas of streptozotocin (STZ)-induced diabetic rats. Glibenclamide was used as a standard reference drug. Oral administration of ethanolic extract at a concentration of 300 mg kg(-1) body weight for 21 days resulted in a significant reduction in fasting blood glucose, thiobarbituric acid reactive substances, hydroperoxides and alpha-tocopherol and significant improvement in ascorbic acid, reduced glutathione and insulin in the plasma of diabetic rats. Similarly, the treatment also resulted in a significant reduction in thiobarbituric acid reactive substances, hydroperoxides, superoxide dismutase, catalase and glutathione peroxidase and significant improvement in reduced glutathione in the pancreas of STZ-induced diabetic rats when compared with untreated diabetic rats. The ethanolic extract appeared to be more effective than glibenclamide in controlling oxidative stress. Thus, this study confirms the ethnopharmacological use of Aloe vera in ameliorating the oxidative stress found in diabetes.     

BENAZEPRIL, AN ANGIOTENSIN-CONVERTING ENZYME INHIBITOR, ALLEVIATES RENAL INJURY IN SPONTANEOUSLY HYPERTENSIVE RATS BY INHIBITING ADVANCED GLYCATION END-PRODUCT-MEDIATED PATHWAYS

• 1 Advanced glycation end‐products (AGE) and their receptors (RAGE) have been implicated in renal damage in diabetes. The aim of the present study was to investigate the effects of benazepril, an angiotensin‐converting enzyme inhibitor (ACEI), on the formation of AGE, the expression RAGE and other associated components in the oxidative stress pathway in spontaneously hypertensive rats (SHR).
• 2 Groups of SHR were treated with or without 10 mg/kg per day benazepril for 12 weeks. Systolic blood pressure (SBP) and angiotensin (Ang) II levels were evaluated in SHR and control Wistar‐Kyoto (WKY) rats. Renal function was investigated by determining levels of proteinuria and glomerulosclerosis. Furthermore, reactive oxygen species (ROS) in the rat renal cortex were analysed using an H₂O₂‐based hydroxyl radical‐detection assay and the renal content of AGE, RAGE, NADPH oxidase p47phox, nuclear factor (NF)‐κB p65, phosphorylated (p‐) NF‐κB p65, vascular cell adhesion molecule (VCAM)‐1 and transforming growth factor (TGF)‐β1 was determined by immunohistochemistry, quantitative real‐time polymerase chain reaction and western blot analysis.
• 3 Treatment with benazepril inhibited the formation of AngII, reduced SBP and alleviated renal lesions in SHR compared with both untreated SHR and control WKY rats. Benazepril treatment significantly suppressed the accumulation of AGE and expression of RAGE in the kidney of SHR. In addition, benazepril treatment reduced the upregulation of NADPH oxidase p47phox, ROS generation and NF‐κB p65, p‐NF‐κB p65, VCAM‐1 and TGF‐β1 expression in the kidney of SHR compared with both untreated SHR and control WKY rats.
• 4 The results of the present study provide new insights into the regulation by the renin–angiotensin system of AGE–RAGE, oxidative stress and nephropathy, increasing our understanding of the role of the RAS in nephropathy.

     

Oxidative damage to nuclear DNA in streptozotocin-diabetic rat liver

1. Accumulating evidence suggests that oxidative and glycative stress is enhanced in diabetes. Oxidative stress induces DNA damage. In the present study, we assessed the 8-oxo-2'-deoxyguanosine (8-oxodG) content of DNA, an indicator of oxidative DNA damage, in streptozotocin (STZ)-induced diabetic (n = 21) and control rats (n = 18). 2. Rats were rendered diabetic by intraperitoneal administration of STZ at a dose of 65 mg/kg. Glucose was determined by glucose oxidase and glycated haemoglobin (GHb), an indicator of glycative stress, was determined by agarose-boronate affinity chromatography. 8-Oxo-2'-deoxyguanosine within the DNA (ratio of 8-oxodG to deoxyguanosine (dG)) was assessed by HPLC in conjunction with both electrochemical (8-oxodG) and diode array (dG) detection. 3. Glucose, GHb and the extent of oxidative DNA damage in the liver of STZ-diabetic rats were much higher compared with control rats. There was a correlation between GHb and 8-oxodG/10(5) dG levels in control (r = 0.756, P < 0.001) and diabetic groups (r = 0.468, 0.02 < P < 0.05). 4. These results clearly show that oxidative damage to hepatic nuclear DNA increases in the diabetic state and that this increase is correlated with glycative stress.     

Protective effect of sun ginseng against diabetic renal damage

The effect of sun ginseng (SG, heat-processed Panax ginseng C. A. MEYER at 120 degrees C) on diabetic renal damage was investigated using streptozotocin-induced diabetic rats. The diabetic rats showed loss of body weight gain, and increases in food and water intake and urine volume, while the oral administration of SG at a dose of 50 or 100 mg/kg body weight/d for 15 d attenuated water intake and urine excretion induced by diabetes. In addition, the diabetic rats given SG at a dose of 100 mg/kg body weight showed significant decreases in serum glucose, serum glycosylated protein and urinary protein levels, suggesting that SG improves the abnormal conditions that lead to oxidative stress. Furthermore, SG significantly reduced advanced glycation endproduct (AGE) formation and thiobarbituric acid-reactive substance levels elevated in the kidneys of diabetic rats. This implies that SG would alleviate the oxidative stress under diabetes through the inhibition of lipid peroxidation. SG also reduced the overexpression of cyclooxygenase-2 and inducible nitric oxide synthase in the kidney induced by hyperglycemia via deactivation the activation of nuclear factor-kappa B. Furthermore, treatment with SG decreased the levels of 3-nitrotyrosine, carboxymethyllysine and receptors for AGE which increase under diabetes. These findings indicate that oxidative stress is increased in the diabetic rat kidney and that SG can prevent renal damage associated with diabetes by attenuating the oxidative stress.     

咖啡对糖尿病大鼠胰岛素分泌、敏感性及氧化应激影响

目的评价咖啡对链脲佐菌素（STZ）诱导的糖尿病大鼠胰岛素敏感性、氧化应激指标及胰腺内胰岛素含量的影响。方法 Wistar大鼠48只,随机分为正常对照组（NC组）、含咖啡因咖啡灌胃组（CC）、去咖啡因咖啡灌胃组（DC）、STZ模型组（S）。CC组和DC组分别以咖啡和去咖啡因咖啡每日灌胃,8周后CC组、DC组、S组均腹腔注射STZ 10 mg kg-1,行口服葡萄糖耐量试验（OGTT）及胰岛素耐量试验（ITT）,测定血浆8-异前列腺素F2α（8-isoPGF2α）和8-羟脱氧鸟苷（8-OHDG）水平,检测胰腺内胰岛素含量。结果 OGTT CC组、DC组、S组均较NC组血糖明显升高。ITT结果 DC组和CC组ITT 30、60、120 min血糖下降比例明显高于S组、与NC组比较血糖下降比例无显著差异。CC组、DC组、S组血浆8-isoPGF2α和8-OHDG水平较NC组明显升高,CC组和DC组8-isoPGF2α和8-OHDG水平显著低于S组。CC组、DC组、S组胰腺内胰岛素含量较NC组显著降低,CC组胰腺内胰岛素水平明显高于DC组和S组。结论含咖啡因咖啡和去咖啡因咖啡均可增加糖尿病大鼠胰岛素敏感性、改善氧化应激;含咖啡因咖啡可增加内源性胰岛素分泌。本研究结果提示含咖啡因和去咖啡因咖啡都可能通过影响氧化应激参与调节糖代谢,含咖啡因咖啡可改善糖尿病大鼠B细胞分泌功能。     

C16, a novel advanced glycation endproduct breaker, restores cardiovascular dysfunction in experimental diabetic rats

AIM: Advanced glycation endproducts (AGE) have been implicated in the pathogenesis of diabetic complications, including diabetic cardiovascular dysfunction. 3-[2-(4-Bromo-phenyl)-1-methyl-2-oxo-ethyl]-4,5,6,7-tetrahydro-benzothiazol-3-ium bromide (C16), a novel AGE breaker, was investigated for its effects on the development of cardiovascular disease in diabetic rats. METHODS: Rats that had streptozotocin-induced diabetes for 12 weeks were divided into groups receiving C16 or vehicle by gavage. RESULTS: In hemodynamic studies of the left ventricle, C16 treatment (25 or 50 mg/kg) for 4 weeks resulted in a significant increase in left ventricular systolic pressure, +dp/dt(max), and -dp/dt(max) as compared with vehicle-treated diabetic rats. Furthermore, in hemodynamic studies of the cardiovascular system, C16 (12.5, 25, or 50 mg/kg) treatment for 4 weeks resulted in a dose-dependent and significant increase in cardiac output, a reduction of total peripheral resistance, and an increase in systemic arterial compliance when compared with vehicle-treated diabetic rats. Biochemical studies showed that C16 treatment also resulted in a significant decrease in immunoglobulin G-red blood cell surface crosslink content and an increase in collagen solubility. Morphological and immunohistochemical examinations indicated that C16 was able to prevent increases of the collagen type III/I ratio in the aorta and decrease the accumulation of AGE in the aorta. Conclusion: C16 has the ability to reduce AGE accumulation in tissues in vivo, and can restore diabetes-associated cardiovascular disorders in rats. This provides a potential therapeutic approach for cardiovascular disease associated with diabetes and aging in humans.     

Treatment with hydrogen sulfide alleviates streptozotocin-induced diabetic retinopathy in rats

Background and Purpose

Retinopathy, as a common complication of diabetes, is a leading cause of reduced visual acuity and acquired blindness in the adult population. The aim of present study was to investigate the therapeutic effect of hydrogen sulfide on streptozotocin (STZ)-induced diabetic retinopathy in rats.

Experimental Approach

Rats were injected with a single i.p. injection of STZ (60 mg·kg⁻¹) to induce diabetic retinopathy. Two weeks later, the rats were treated with NaHS (i.p. injection of 0.1 mL·kg⁻¹·d⁻¹ of 0.28 mol·L⁻¹ NaHS, a donor of H₂S) for 14 weeks.

Key Results

Treatment with H₂S had no significant effect on blood glucose in STZ-induced diabetic rats. Treatment with exogenous H₂S enhanced H₂S levels in both plasma and retinas of STZ-induced diabetic rats. Treatment with H₂S in STZ-treated rats improved the retinal neuronal dysfunction marked by enhanced amplitudes of b-waves and oscillatory potentials and expression of synaptophysin and brain-derived neurotrophic factor, alleviated retinal vascular abnormalities marked by reduced retinal vascular permeability and acellular capillary formation, decreased vitreous VEGF content, down-regulated expressions of HIF-1α and VEGFR2, and enhanced occludin expression, and attenuated retinal thickening and suppressed expression of extracellular matrix molecules including laminin β1 and collagen IVα3 expression in retinas of STZ-induced diabetic rats. Treatment with H₂S in retinas of STZ-induced diabetic rats abated oxidative stress, alleviated mitochondrial dysfunction, suppressed NF-κB activation and attenuated inflammation.

Conclusions and Implications

Treatment with H₂S alleviates STZ-induced diabetic retinopathy in rats possibly through abating oxidative stress and suppressing inflammation.