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1.
Guoguo Shang Pan Gao Zhonghua Zhao Qi Chen Tao Jiang Nong Zhang Hui Li 《生物化学与生物物理学报:疾病的分子基础》2013,1832(5):674-684
3, 5-Diiodothyronine (T2), a natural metabolite of triiodothyronine (T3) from deiodination pathway, can mimic biologic effects of T3 without inducing thyrotoxic effects. Recent studies revealed T3 acted as a protective factor against diabetic nephropathy (DN). Nevertheless, little is known about the effect of T2 on DN. This study was designed to investigate whether and how T2 affects experimental models of DN in vivo and in vitro. Administration of T2 was found to prevent significant decrease in SIRT1 protein expression and activity as well as increases in blood glucose, urine albumin excretion, matrix expansion, transforming growth factor-β1 expression, fibronectin and type IV collagen deposition in the diabetic kidney. Concordantly, similar effects of T2 were exhibited in the cultured rat mesangial cells (RMC) exposed to high glucose and that could be abolished by a known SIRT1 inhibitor, sirtinol. Moreover, enhanced NF-κB acetylation and JNK phosphorylation present in both diabetic rats and high glucose-treated RMC were distinctly dampened by T2. Collectively, these results suggested that T2 was a protective agent against renal damage in diabetic nephropathy, whose action involved regulation of SIRT1. 相似文献
2.
C E Mogensen 《BMJ (Clinical research ed.)》1982,285(6343):685-688
Six men aged 26-35 years with proteinuria due to insulindependent juvenile-onset diabetes were treated for moderate hypertension (mean blood pressure 162/103 mm Hg) and studied for a mean of 73 months for the effect on the progression of nephropathy. All patients were of normal weight. During a mean control period of 28 months before treatment the mean glomerular filtration rate (three or four measurements) was 86·1 ml/min and mean 24-hour urinary albumin excretion (also three or four measurements) 3·9 g (range 0·5-8·8 g).During antihypertensive treatment the mean systolic blood pressure fell to 144 mm Hg and mean diastolic pressure to 95 mm Hg. In the control period five patients had shown a mean monthly decline in glomerular filtration rate of 1·23 ml/min; with antihypertensive treatment, however, this decline fell to 0·49 ml/min (2p=0·042). In the remaining patient the glomerular filtration rate was 137 ml/min before treatment and 135 ml/min at the end of the treatment period. In all patients the mean yearly increase in albumin clearance (expressed as a percentage of the glomerular filtration rate) fell from 107% before treatment to 5% during treatment (2p=0·0099).This small study indicates that antihypertensive treatment slows the decline in renal function in diabetic nephropathy. Clinical trials beginning treatment in the incipient phase of diabetic nephropathy will define the optimal modality of treatment in this large patient population. 相似文献
3.
Long-term taurine supplementation reduces mortality rate in streptozotocin-induced diabetic rats 总被引:4,自引:0,他引:4
Summary. Oxidative stress is implicated in the pathogenesis of diabetes mellitus. Taurine and vitamin E+selenium supplementation has some benefits in experimental models of diabetes mellitus. This study evaluates whether taurine and vitamin E+selenium supplementations reduce a hard end-point such as mortality due to diabetes. Streptozotocin-induced diabetic rats were fed with standard diet or taurine (5%, w/w) or vitamin E (500UI/Kg)+selenium (8mg/Kg) enriched diets. Taurine significantly decreased mortality rate (p<0.04), while vitamin E failed to increase survival. In the late phase of the disease, taurine significantly decreased glycaemia, being vitamin E ineffective. No correlation between glycaemia and survival was found. None of supplementations modified body weight. Thus, only taurine decreases the mortality rate and glycaemia. These results encourage new research in the field, since classical hypoglycaemic agents are unable to decrease mortality in diabetic patients. 相似文献
4.
Diabetic nephropathy (DN) is a microvascular complication associated with diabetes causing slow deterioration of kidneys leading to end-stage renal disease. Timely intervention and diagnosis are crucial in order to ameliorate and halt the progression of DN. Current diagnosis of DN consists of urine assays for detection of microalbuminuria, which have inadequate specificity and sensitivity. Hence, there arises a need to discover stage-specific biomarkers which can aid in the early detection of DN and also in identifying the mechanisms underlying pathogenesis of DN. Therefore the present study was undertaken to identify the differentially expressed proteins in the urine and to examine the pattern of proteomic changes occurring in the rat kidneys during the course of progression of streptozotocin-induced model of DN in rats. Two-dimensional gel electrophoresis coupled to MALDI-TOF mass spectrometry was employed to identify the differentially expressed proteins under diabetic conditions. Among the identified proteins Calgranulin A and Calgranulin B appeared in the urinary proteome at the fourth week of induction of diabetes while we recorded a time-dependent decrease in the expression of major urinary protein (alpha 2u globulin) in the urine as well as kidneys of diabetic rats. Parallel monitoring of targeted proteomic changes in the renal proteome revealed an increase in histone H2B phosphorylation at serine14 along with a gradual decrease in Bcl-2 and MMP-13 expression during the course of progression and development of streptozotocin-induced DN. 相似文献
5.
Alteration of antioxidants during the progression of heart disease in streptozotocin-induced diabetic rats 总被引:6,自引:0,他引:6
Doi K Sawada F Toda G Yamachika S Seto S Urata Y Ihara Y Sakata N Taniguchi N Kondo T Yano K 《Free radical research》2001,34(3):251-261
Involvement of oxidative stress is implicated in the progression of complication of diabetes mellitus. With respect to heart diseases, we have studied role of oxidative stress/antioxidants using rats treated with streptozotocin to induce diabetes (DM). Hemodynamic and echocardiographic measurements showed thickening of the wall and an increase in the internal dimension of the left ventricle (LV) in DM rats at 8th week. Decrease in diastolic posterior wall velocity and rate of LV pressure change, and increase in LV end diastolic pressures also proved cardiac dysfunction. These changes were further developed in DM rats after 12 weeks. Utilizing rat hearts at 8th and 12th weeks, the following estimations were performed. There was a decrease in the activity of Mn-superoxide dismutase (SOD), suggesting abnormal mitochondrial metabolism of reactive oxygen species. The level of glutathione (GSH) decreased concomitant with a decrease in the expression of γ-glutamylcysteine synthetase (γ-GCS). The expression of transforming growth factor-β1 (TGF-β1), known as a growth factor and a suppressor of GSH synthesis, elevated in DM rat hearts. Immunohistochemical estimation showed an increase in type IV collagen in DM hearts. Collectively, it was suggested a linkage between mitochondrial damage to generate reactive oxygen species and inactivation of Mn-SOD and elevation of the expression of TGF-β1 to lead suppression of GSH synthesis and induction of fibrous change for the consequent cardiac dysfunction in DM. 相似文献
6.
Kagumi Doi Fumi Sawada Genji Toda Shiro Yamachika Shinji Seto Yoshishige Urata 《Free radical research》2013,47(3):251-261
Involvement of oxidative stress is implicated in the progression of complication of diabetes mellitus. With respect to heart diseases, we have studied role of oxidative stress/antioxidants using rats treated with streptozotocin to induce diabetes (DM). Hemodynamic and echocardiographic measurements showed thickening of the wall and an increase in the internal dimension of the left ventricle (LV) in DM rats at 8th week. Decrease in diastolic posterior wall velocity and rate of LV pressure change, and increase in LV end diastolic pressures also proved cardiac dysfunction. These changes were further developed in DM rats after 12 weeks. Utilizing rat hearts at 8th and 12th weeks, the following estimations were performed. There was a decrease in the activity of Mn-superoxide dismutase (SOD), suggesting abnormal mitochondrial metabolism of reactive oxygen species. The level of glutathione (GSH) decreased concomitant with a decrease in the expression of γ-glutamylcysteine synthetase (γ-GCS). The expression of transforming growth factor-β1 (TGF-β1), known as a growth factor and a suppressor of GSH synthesis, elevated in DM rat hearts. Immunohistochemical estimation showed an increase in type IV collagen in DM hearts. Collectively, it was suggested a linkage between mitochondrial damage to generate reactive oxygen species and inactivation of Mn-SOD and elevation of the expression of TGF-β1 to lead suppression of GSH synthesis and induction of fibrous change for the consequent cardiac dysfunction in DM. 相似文献
7.
Banki NF Ver A Wagner LJ Vannay A Degrell P Prokai A Gellai R Lenart L Szakal DN Kenesei E Rosta K Reusz G Szabo AJ Tulassay T Baylis C Fekete A 《PloS one》2012,7(6):e39938
Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers. 相似文献
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9.
This study investigated the effect of Phellodendri Cortex extract on hyperglycemia and diabetic nephropathy in streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into normal control (NC), diabetic control (DC), and diabetic treatment with Phellodendri Cortex extract (DP). Over a 4-week experimental period, Phellodendri Cortex extract was administered orally at 379 mg/kg BW/day. The final fasting serum glucose level, urine total protein level, and relative left kidney weight in the DP group were significantly lower than the DC group. Renal XO and SOD activities in the DP group were significantly lower than the DC group and renal CAT activity in the DP group was significantly higher than the DC group. Tubular epithelial change was reduced in the DP group compared to the DC group. These results indicated that Phellodendri Cortex can reduce glucose level and prevent or retard the development of diabetic nephropathy in streptozotocin-induced diabetic rats. 相似文献
10.
Red wine prevents brain oxidative stress and nephropathy in streptozotocin-induced diabetic rats 总被引:2,自引:0,他引:2
Montilla P Barcos M Munoz MC Bujalance I Munoz-Castaneda JR Tunez I 《Journal of biochemistry and molecular biology》2005,38(5):539-544
We have studied the effects of red wine on brain oxidative stress and nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Wistar rats with a single intraperitonally injection of STZ (50 mg/kg). Two weeks before and four weeks after injection, red wine was given orally in both normal and diabetic rats. Blood samples were taken from the neck vascular trunk in order to determine the glucose, triglycerides, total cholesterol, HDL-cholesterol (HDL-c), atherogenic index (AI), total protein, blood urea nitrogen (BUN), creatinine, insulin, lipid peroxidation products, reduced glutathione (GSH) and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. As well, we estimated the lipid peroxidtion, GSH and SOD, GSH-Px and catalase activities in brain and renal homogenates, and the excretion of albumin, proteins and glucose in urine over 24 h period. The administration of STZ caused significant increases in levels of glycosuria, proteinuria, albuminuria, glycemia, total cholesterol and AI, as well as in lipid peroxidation products in the brain, plasma and kidney, whereas it decreased the GSH content and SOD, GSH-Px and catalase activities. Treatment with red wine significantly prevented the changes induced by STZ. These data suggested that red wine has a protective effect against brain oxidative stress, diabetic nephropathy and diabetes induced by STZ, as well as it protects against hypercholesterolemia and atherogenic risk. 相似文献
11.
Yunan Tang Qin Yang Jiayin Lu Xiaolin Zhang Di Suen Yi Tan Litai Jin Jian Xiao Rujia Xie Madhavi Rane Xiaokun Li Lu Cai 《The Journal of nutritional biochemistry》2010,21(3):237-246
We have demonstrated that Zn supplementation mediated up-regulation of cardiac metallothionein (MT) as a potent antioxidant prevented the development of diabetic cardiomyopathy. The present study was undertaken to test whether induction of renal MT synthesis by Zn supplementation protects the kidney from diabetes-induced damage. Streptozotocin-induced diabetic rats were treated with and without Zn supplementation at 5 mg/kg in drinking water for 3 months. Diabetic renal damage was detected by examining renal pathological alterations and 24-h urinary protein levels. Three-month Zn supplementation immediately after the onset of diabetes, partially but significantly, prevented the kidney from diabetes-induced increases in 24-h urinary proteins and pathological alterations. Diabetes-induced renal oxidative damage, inflammation and up-regulated expression of profibrosis mediator connective tissue growth factor (CTGF) were also markedly attenuated by Zn supplementation, along with significant increases in Zn levels concomitant with MT expression in renal tubular cells. Direct exposure of renal tubular (HK11) cells to high levels of glucose (HG) induced CTGF up-regulation predominantly through ERK (extracellular signal-regulated kinase)1/2-dependent, and partially through p38 mitogen-activated protein kinase (MAPK)-dependent pathways. Pretreatment of HK11 cells with Zn or cadmium induced MT expression and also significantly suppressed HG-induced CTGF expression. These results provide the first evidence for Zn supplementation to attenuate diabetes-induced renal pathological changes, likely through prevention of hyperglycemia-induced CTGF expression by Zn-induced MT in renal tubular cells. 相似文献
12.
Li Chen Guibin Mei Chunjie Jiang Xueer Cheng Dan Li Ying Zhao Huimin Chen Cheng Wan Ping Yao Chao Gao Yuhan Tang 《Cell proliferation》2021,54(6)
ObjectivesSenescence, characterized by permanent cycle arrest, plays an important role in diabetic nephropathy (DN). However, the mechanism of renal senescence is still unclear, and the treatment targeting it remains to be further explored.Materials and MethodsThe DN mice were induced by HFD and STZ, and 3 types of renal cells were treated with high glucose (HG) to establish in vitro model. Senescence‐related and autophagy‐related markers were detected by qRT‐PCR and Western blot. Further, autophagy inhibitors and co‐immunoprecipitation were used to clarify the mechanism of CO. Additionally, the specific relationship between autophagy and senescence was explored by immunofluorescence triple co‐localization and ELISA.ResultsWe unravelled that senescence occurred in vivo and in vitro, which could be reversed by CO. Mechanistically, we demonstrated that CO inhibited the dysfunction of autophagy in DN mice partly through dissociating Beclin‐1‐Bcl‐2 complex. Further results showed that autophagy inhibitors blocked the improvement of CO on senescence. In addition, the data revealed that autophagy regulated the degradation of senescence‐related secretory phenotype (SASP) including Il‐1β, Il‐6, Tgf‐β and Vegf.ConclusionsThese results suggested that CO protects DN mice from renal senescence and function loss via improving autophagy partly mediated by dissociating Beclin‐1‐Bcl‐2 complex, which is possibly ascribed to the degradation of SASP. These findings bring new ideas for the prevention and treatment of DN and the regulation of senescence. 相似文献
13.
Diabetic nephropathy is the common cause of leading to end stage of renal disease (ESRD). Satureja khozestanica essential oil (SKEO) was used as an antioxidant and antidiabetic for the inhibition of diabetic nephropathy. Forty male rats were uninephrectomized and divided in four groups randomly; group one as control, group two diabetic untreatment, groups three and four treatment with SKEO by 250 or 500 ppm in drinking water, respectively. Diabetes was induced in the second, third and fourth groups by alloxan injection subcutaneously. After eight weeks treatment, serum malondialdehyde, serum creatinine and serum urea were measured. The kidney paraffin sections were stained by periodic acid Schiff method. Glomerular volume and glomerular number were estimated by stereological rules. Glomerular sclerosis was studied semi-quantitatively. The means were compared by SPSS 13 software and Mann-Whitney test at p < 0.05. Satureja khozestanica essential oil (250 or 500 ppm) significantly inhibited the progression of glomerular hypertrophy, glomerular number loss, glomerulosclerosis, lipid peroxidation, serum urea and creatinine compared with the diabetic untreated group. The level of glomerular number, serum malondialdehyde, serum creatinine and urea in the treated groups was significantly maintained at the same level as that of the control group. In conclusion, satureja essential oil significantly can ameliorate glomerular hypertrophy, loss of glomerular number, glomerulosclerosis and attenuated serum urea and serum creatinine in diabetic rats. 相似文献
14.
Qiang Shi Jianchao Wang Yuhong Cheng Xiaomin Dong Ming Zhang Cheng Pei 《Journal of biochemical and molecular toxicology》2020,34(7)
Diabetic retinopathy (DR) is the primary cause of blindness and visual impairment in diabetes patients worldwide. However, laser and surgical therapies at DR have short‐term effectiveness and cause side effects. Treatment with natural products is a reasonable alternative treatment for DR. The main objective of this investigation is to explore the efficacy of a bioactive compound such as palbinone (PB) in DR. Experimental rats were injected intraperitoneally with streptozotocin (STZ, 65 mg/kg), and these established experimental rats were treated with PB (20 mg/kg/bw) for 42 days. The observed results showed that PB considerably reduced the proinflammatory cytokine (interleukin‐18 [IL‐18] and IL‐1β) production as well as improved the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) particularly in the retinal region of STZ‐induced DR rats. In addition, PB treatment improved nuclear factor erythroid 2‐related factor 2 (Nrf2) accumulation and enhanced the heme oxygenase‐1 expression, and major antioxidants downregulated Nrf2 in the damaged retina. Also, the expression levels of nod‐like receptor family pyrin domain containing 3 (NLRP3), cleaved‐caspase‐1, IL‐1β, and apoptosis‐associated speck‐like protein containing CARD in the retinal region were notably upregulated in STZ‐induced DR, which was eliminated by PB interference. PB administration exerted efficient antioxidant activities, Nrf2 pathway activation, and inhibition of NLRP3 inflammasome. This current investigation concluded that PB considerably reduced the retinal inflammation and oxidative stress stimulated via high glucose, and also activated the antioxidative Nrf2 pathway and inhibited the NLRP3 inflammasome formation in rats. 相似文献
15.
目的探讨补充益生菌对老年糖尿病肾病患者疾病进展风险的影响。方法选取我院2016年2月至2017年3月老年糖尿病肾病患者90例,按随机数字表法分为对照组(n=45)和益生菌组(n=45),对照组予以常规治疗,益生菌组在对照组的治疗基础上补充益生菌。比较两组患者治疗前后的血糖控制、血脂、肾功能指标、相关炎症及应激反应因子的水平,随访24个月,比较两组患者糖尿病肾病进展情况,应用Cox回归分析探讨老年糖尿病肾病患者疾病进展的相关影响因素。结果治疗前,比较两组患者血糖控制、血脂、肾功能指标和相关氧化应激反应的水平,差异均无统计学意义(均P0.05)。治疗后,益生菌组患者空腹血糖、餐后2 h血糖、低密度脂蛋白胆固醇(LDL-C)、糖化血红蛋白(HbA1c)、血肌酐(Scr)、血尿素氮(BUN)、胱抑素C(Cys C)、24 h尿蛋白水平明显低于对照组(均P0.05),高密度脂蛋白胆固醇(HDL-C)水平明显高于对照组(P0.001)。两组患者的炎症及应激反应因子水平较治疗前明显降低,其中益生菌组C-反应蛋白(CRP)、丙二醛(MDA)水平明显低于对照组(均P0.05);谷胱甘肽过氧化物酶(GSH-PX)、一氧化氮(NO)、总抗氧化能力(TAC)明显高于对照组(均P0.05)。益生菌组的进展率为40.0%,明显低于对照组的57.8%(P0.05)。Cox回归分析显示,补充益生菌、24 h尿蛋白1.5 g、HbA1c、Cys C是老年性糖尿病肾病患者疾病进展的风险因素(均P0.05)。结论补充益生菌能明显改善老年糖尿病肾病患者的血糖、血脂状况和肾功能,降低炎症反应水平,显著降低老年糖尿病肾病患者的疾病进展风险。 相似文献
16.
Kazuo Ohtake Yuichi Ishiyama Hiroyuki Uchida Etsuko Muraki Jun Kobayashi 《Nitric oxide》2007,17(2):75-81
Increased production of reactive oxygen species (ROS) is a key event leading to microvascular complications, including nephropathy, in diabetes mellitus (DM). Excessive ROS and oxidative stress in DM have been reported to be associated with subsequent impaired nitric oxide (NO) bioavailability. The aim of this study is to examine the beneficial function of dietary nitrite supplementation as an interventional NO donor to attenuate early progression of diabetic nephropathy. To test this hypothesis, male Sprague-Dawley rats were randomly divided into four groups: non-diabetic rats given water with or without nitrite (nitrite-treated or untreated, respectively), and streptozotocin-induced diabetic rats given water with or without nitrite (nitrite-treated or untreated, respectively). After a 4 week experimental period, untreated diabetic rats exhibited significantly higher malondialdehyde (MDA) levels in the kidney compared with untreated non-diabetic rats, accompanied by a reduction in levels of endogenous NO synthase-derived nitrite. However, dietary nitrite supplementation to diabetic rats not only decreased MDA levels but also increased nitrite levels in the kidney to the same levels as in the non-diabetic kidney. These improvements accompanied an improvement in the parameters of glomerular injury, including urinary protein and albumin excretion, histopathological glomerular hypertrophy, and mesangial matrix accumulation. These results indicate that dietary nitrite is effective in the prevention of early diabetic glomerular injury in which NO bioavailability is impaired. 相似文献
17.
Diabetic nephropathy (DN) is one of the serious secondary complications of diabetes, which results in end-stage renal failure. Reports on the progressive nature of early phase DN especially with respect to kidney parameters such as kidney weight, type IV collagen excretion, total kidney and urinary glycosaminoglycans (GAGs) are few. This work was undertaken to determine systematically the progression of early phase DN in relation to various kidney-related parameters for a period of four months. Experimentally-induced diabetic rats were grouped based on fasting blood glucose levels. Various basic and kidney-related parameters such as kidney weight, microalbuminuria, urinary excretion of GAGs and type IV collagen, total kidney GAGs, histopathology, glomerular area and glomerular volume were examined in control and diabetic rats. There was a progressive increase in fasting blood sugar, urine sugar, kidney weight, microalbuminuria, urine glycosaminoglycans, urine type IV collagen, glomerular area and glomerular volume but there was a progressive decrease in kidney glycosaminoglycans. Glomerular sclerotic condition was aggravated with the increase in duration of diabetes from 1 to 4 months. Onset of DN in rats begins subtly after one month of diabetes but gets vitiated and more pronounced at the end of four months. 相似文献
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19.
Type 2 diabetes mellitus (T2DM) is a chronic and one of the most common metabolic diseases affecting large proportion of world population. Diabetes-induced changes in lipid and renal parameters are major risk factors contributing to diabetic complications such as diabetic nephropathy and cardiovascular diseases. Due to adverse effects associated with pharmacological intervention in the T2DM treatment, there is an increased interest in the research focussing on identifying novel plant based therapeutic agents. Here we report the effects of various coconut products on diabetic, lipid and renal parameters in streptozotocin (STZ)-induced diabetic rat model. Diabetic rats demonstrated a significant increase in serum glucose, and glycated haemoglobin levels (HbA1c). Lipid parameters including triglycerides, total cholesterol, low density lipoprotein cholesterol (LDL-cholesterol) and very low density lipoprotein cholesterol (VLDL-cholesterol) were found to be significantly increased, while high density lipoprotein cholesterol (HDL-cholesterol) was significantly declined in diabetic rats. Diabetic rats also displayed increased serum and kidney creatinine, urea, and total protein levels and increased urine glucose, urea, albumin and creatinine levels. Contrastingly, treatment with virgin and filtered coconut oils, coconut water and coconut milk resulted in a significant reversal in the levels of above studied parameters in diabetic rats. Further, these coconut products markedly prevented diabetes induced histopathological changes in kidney tissue. Collectively, the data demonstrate the antidiabetic, hypolipidemic and renal protective properties of various coconut products and underscore the importance of regular consumption of plant based medicinal products in the treatment of T2DM and its complications. 相似文献
20.
《Phytomedicine》2014,21(5):734-739
Chronic hyperglycemia leads to the formation of advanced glycation end products (AGEs), which accelerates the development of diabetic complications. Previous studies have shown that extract of Cassiae semen (CS), the seed of Cassia tora, has inhibitory activity on AGEs formation in vitro and reduces transforming growth factor-beta1 (TGF-β1) and extracellular matrix protein expression via inhibition of AGEs-mediated signaling in glomerular mesangial cells. In this study, to examine the preventive effects of CS extract on the development of diabetic nephropathy in vivo, streptozotocin (STZ)-injected diabetic rats were orally administered CS extract (200 mg/kg body weight/day) for 12 weeks. Serum glucose, triglycerides, and total cholesterol in diabetic rats were significantly higher compared to control rats. CS or aminoguanidine (AG) treatment significantly reduced these factors. Proteinuria and creatinine clearance were also significantly decreased in the CS-treated group compared with the untreated diabetic group. The CS-treated group had significantly inhibited COX-2 mRNA and protein, which mediates the symptoms of inflammation in the renal cortex of diabetic rats. Furthermore, histopathological studies of kidney tissue showed that in diabetic rats, AGEs, the receptor for AGEs, TGF-β1, and collagen IV were suppressed by CS treatment. Our data suggest that oral treatment of CS can inhibit the development of diabetic nephropathy via inhibition of AGEs accumulation in STZ-induced diabetic rats. 相似文献