scholarly journals Decrease of Klotho in the Kidney of Streptozotocin-Induced Diabetic Rats

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Meng-Fu Cheng ◽  
Li-Jen Chen ◽  
Juei-Tang Cheng

Theklothogene is expressed in a limited number of tissues, most notably in distal convoluted tubules in the kidney and choroid plexus in the brain. A previous study suggested that Klotho increases resistance to oxidative stress. However, changes of Klotho expression in high glucose-induced oxidative stress remain unclear. In the present study, we used streptozotocin-induced diabetic rats (STZ rats) to examine the effects of insulin, phloridzin or antioxidant, tiron on diabetic nephropathy. Both insulin and phloridzin reversed the lower Klotho expression levels in kidneys of STZ rats by the correction of hyperglycemia. Also, renal functions were improved by these treatments. In addition to the improvement of renal functions, the decrease of Klotho expression in kidney of STZ rats was also reversed by tiron without changing blood glucose levels. The reduction of oxidative stress induced by high glucose can be considered for this action of tiron. This view was further confirmed in vitro using high glucose-exposed Madin-Darby canine kidney (MDCK) epithelial cells. Thus, we suggest that decrease of oxidative stress is not only responsible for the improvement of renal function but also for the recovery of Klotho expression in kidney of STZ rats.

2011 ◽  
Vol 13 (1) ◽  
pp. 56-66 ◽  
Author(s):  
Bruno S Pessôa ◽  
Elisa BMI Peixoto ◽  
Alexandros Papadimitriou ◽  
Jacqueline M Lopes de Faria ◽  
José B Lopes de Faria

Spironolactone (SPR), a mineralocorticoid receptor blocker, diminishes hyperglycemia-induced reduction in glucose-6-phosphate dehydrogenase (G6PD) activity, improving oxidative stress damage. This study investigated whether SPR ameliorates nephropathy by increasing G6PD activity and reducing oxidative stress in spontaneously hypertensive diabetic rats (SHRs). The streptozotocin-induced diabetic rats received or not SPR 50 mg/kg per day, for eight weeks. A human mesangial cell line was cultured in normal or high glucose conditions, with or without SPR, for 24 h. Plasma glucose levels and systolic blood pressure were unaltered by diabetes or by SPR treatment. Albuminuria, fibronectin expression, 8-OHdG urinary levels, lipid peroxidation and p47phox expression were higher in the diabetic rats compared with the control and were reduced by SPR. The antioxidant GSH/GSSG ratio was reduced in the diabetic rats and the treatment reestablished it. Diabetes-induced SGK1 up-regulation was inhibited by SPR. Reactive oxygen species (ROS) and superoxide production induced by NADPH oxidase were increased by hyperglycemia and high glucose, in vivo and in vitro, respectively, and were reduced with SPR. Hyperglycemia and high glucose decreased G6PD activity, which was restored with SPR. These results suggest that SPR ameliorates nephropathy in diabetic SHRs by restoring G6PD activity and diminishes oxidative stress without affecting glycaemia and blood pressure.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 335
Author(s):  
Estefanía Bravo-Sánchez ◽  
Donovan Peña-Montes ◽  
Sarai Sánchez-Duarte ◽  
Alfredo Saavedra-Molina ◽  
Elizabeth Sánchez-Duarte ◽  
...  

Diabetes mellitus (DM) constitutes one of the public health problems today. It is characterized by hyperglycemia through a defect in the β-cells function and/or decreased insulin sensitivity. Apocynin has been tasted acting directly as an NADPH oxidase inhibitor and reactive oxygen species (ROS) scavenger, exhibiting beneficial effects against diabetic complications. Hence, the present study’s goal was to dissect the possible mechanisms by which apocynin could mediate its cardioprotective effect against DM-induced oxidative stress. Male Wistar rats were assigned into 4 groups: Control (C), control + apocynin (C+A), diabetes (D), diabetes + apocynin (D+A). DM was induced with streptozotocin. Apocynin treatment (3 mg/kg/day) was applied for 5 weeks. Treatment significantly decreased blood glucose levels and insulin resistance in diabetic rats. In cardiac tissue, ROS levels were higher, and catalase enzyme activity was reduced in the D group compared to the C group; the apocynin treatment significantly attenuated these responses. In heart mitochondria, Complexes I and II of the electron transport chain (ETC) were significantly enhanced in the D+A group. Total glutathione, the level of reduced glutathione (GSH) and the GSH/ oxidized glutathione (GSSG) ratio were increased in the D+A group. Superoxide dismutase (SOD) and the glutathione peroxidase (GSH-Px) activities were without change. Apocynin enhances glucose uptake and insulin sensitivity, preserving the antioxidant defense and mitochondrial function.


Author(s):  
Amine Azzane ◽  
Ayou Amssayef ◽  
Mohame Eddouks

Aims: The aim of the study was to evaluate the antihyperglycemic effect of Chenopodium quinoa. Background: Chenopodium quinoa is a pseudocereal plant with several medicinal properties. Objective: The goal of this investigation was to determine the antihyperglycemic activity of Chenopodium quinoa in both normal and streptozotocin(STZ)-induced diabetic rats. Methods: In this study, the effect of the aqueous extract of Chenopodium quinoa seeds (AECQS) (60 mg/kg) on blood glucose levels was evaluated in both normal and diabetic rats after a single (6 hours) and repeated oral administration (7 days of treatment). The effect of this herb on glucose tolerance and lipid profile was also studied. Additionally, histopathological examination of liver was carried out using the Hematoxylin-Eosin method. Furthermore, the in vitro antioxidant activity as well as a preliminary phytochemical screening and quantification of some secondary metabolites (phenolic compounds, flavonoids and tannins) were performed according to standard methods. Results: AECQS produced a significant lowering effect on plasma glucose levels in STZ-induced diabetic rats. In addition, this extract exhibited a remarkable amelioration on hepatic histopathology in diabetic rats. In addition, the extract exerted a remarkable antioxidant activity which could be due to the presence of some compounds found in this herb. Conclusion: In conclusion, this study demonstrates that the aqueous extract of Chenopodium quinoa seeds has a favorable effect in controlling diabetes mellitus.


2020 ◽  
Vol 8 (1) ◽  
pp. e001426
Author(s):  
Wei Wu ◽  
Jinna Yuan ◽  
Yu Shen ◽  
Yunxian Yu ◽  
Xuefeng Chen ◽  
...  

IntroductionThis study was performed to investigate the role of iron overload in the early stage of hyperglycemia-induced vascular functional impairment.Research design and methodsA total of 196 obese children were enrolled, and data regarding ferritin levels, blood glucose levels, intima-media thickness of carotid arteries, liver function and fibrosis index, hemoglobin, blood pressure, blood lipids, and inflammation indicators were collected. Ferritin levels were compared with a control group, which consisted of 148 healthy non-obese children who were age-matched and gender-matched. Endothelial cells were cultured in high glucose medium and supplemented with ferric citrate with or without iron remover (deferoxamine), a reducing agent (N-acetyl-cysteine), or a nuclear factor-κB (NF-κB) inhibitor (BAY 11-7082). Apoptosis, oxidative stress, nitric oxide levels, and endothelin content were evaluated. DNA microarray analysis was performed to analyze the expression of genes in the NF-κB signaling pathway.ResultsObese children have significantly higher ferritin levels compared with the control group. Ferritin level was positively correlated with hemoglobin and was related to metabolic disorders, including impaired glucose tolerance, higher blood pressure, dyslipidemia, and impaired hepatic function. Endothelial cells treated with ferric citrate showed a significantly higher rate of apoptosis, higher levels of oxidative stress, and impaired vasomotor function under high glucose conditions. The above effects were rescued by treatment with an iron remover, reducing agent, or NF-κB inhibitor. Further, detection of phosphorylated-p65 distribution in cells confirmed activation of the NF-κB pathway. DNA microarrays and subsequent gene oncology enrichment analyses revealed the main processes activated in cells.ConclusionIncreased ferritin levels are related to impaired glucose tolerance and other metabolic disorders in obese children. At the cellular level, iron overload aggravated the endothelial cell dysfunction caused by high glucose.


2000 ◽  
Vol 1 (2) ◽  
pp. 145-153 ◽  
Author(s):  
Sibel Özyazgan ◽  
Yesim Unlucerci ◽  
Selda Bekpinar ◽  
Ahmet Gökhan Akkan

AimThe effect of 8 weeks′ streptozotocin (STZ)- induced diabetes and aminoguanidine (AMNG), the inhibitor of advanced glycosylation reaction, treatment on arteriolar reactivity to vasoactive substances was investigatedin vitro.Materials and MethodsStudies were performed in untreated control rats (n= 10), STZ-induced (60 mg/kg i.v.) diabetic rats (n= 10), AMNG-treated (600 mg/l given in drinking water throughout 8 weeks) control rats (n= 10) and AMNG-treated (600 mg/l given in drinking water, beginning at 72h after STZ and throughout 8 weeks of diabetes) diabetic rats (n= 10). Results are expressed as the mean ±s.e. Relaxant responses are expressed as a percentage (%) relaxation of noradrenaline-induced tone. Statistical comparisons were made by one-way analysis of variance (ANOVA) followed by Tukey–Kramer multiple comparisons test.Results1. The decreased body weights (205 ± 6 g) and increased blood glucose levels (583 ± 8 mg/dl) of diabetic rats were partially restored by treatment of aminoguanidine (253 ± 6 g,p< 0.05 and 480 ± 14 mg/dl,p< 0.001, respectively). 2. Diabetes caused a 71% deficit in maximal endothelium-dependent relaxation to acetylcholine for noradrenaline precontracted aortas (p< 0.001). AMNG treatment prevented the diabetes-induced impairment in endothelium dependent relaxation (58 ± 8%) to acetylcholine, maximum relaxation remaining in the non-diabetic range (78 ± 4%). 3. Neither diabetes nor treatment affected endothelium-independent relaxation (pD2and max. Relax.) to sodium nitroprusside. 4. Vasoconstrictor responses (pD2and Max. Contraction) to noradrenaline and KCl were not influenced by the diabetic state and treatment.ConclusionOur data suggest that 8 weeks of experimental diabetes is associated with a decreased endothelium-dependent vasodilatation. AMNG treatment may prevent diabetes-induced endothelial dysfunction. This may be mediatedviathe prevention of advanced glycosylation end product formation, the enhanced release of vasodilator substances such as prostacyclin, the increased elasticity of blood vessels, the antioxidant activity and inhibitor activity of enzyme aldose-reductase by AMNG.


Author(s):  
Ayoub Amssayef ◽  
Mohammed Ajebli ◽  
Mohamed Eddouks

Aims: The aim of the study was to investigate the antihyperglycemic activity of Matricaria pubescens. Background: Matricaria pubescens (Def). Shultz (Asteraceae) is commonly used traditionally for the treatment of diabetes in Morocco. Objective: This present investigation aimed to assess the antihyperglycemic and antioxidant effects of the aqueous extract of aerial part of Matricaria pubescens (M. pubescens). Methods: The effect of a single and repeated oral administration of the aqueous extract of aerial part of M. pubescens (AEAPMP) at a dose of 40 mg/kg on glucose was examined in normal and streptozotocin-induced diabetic rats. Additionally, histopathological examination of pancreas and liver was carried out according to the Hematoxylin-Eosin method. The antioxidant activity was performed using the DPPH assay. Results: The results showed that the aqueous extract of M. pubescens (AEAPMP) exhibited a significant lowering activity on blood glucose levels in STZ-induced diabetic rats. In addition, AEAPMP ameliorated the histopathological tissues of liver and pancreas. Furthermore, a potential in vitro antioxidant of AEAPMP has been shown. Conclusion: In conclusion, this study demonstrates that M. pubescens possesses a beneficial effect against hyperglycemia associated with diabetes.


Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2812 ◽  
Author(s):  
Adriana Rodríguez-Méndez ◽  
Wendy Carmen-Sandoval ◽  
Consuelo Lomas-Soria ◽  
Ramón Guevara-González ◽  
Rosalía Reynoso-Camacho ◽  
...  

In Mexico one in 14 deaths are caused by diabetes mellitus (DM) or by the macro and microvascular disorders derived from it. A continuous hyperglycemic state is characteristic of DM, resulting from a sustained state of insulin resistance and/or a dysfunction of β-pancreatic cells. Acaciella angustissima is a little studied species showing a significant antioxidant activity that can be used as treatment of this disease or preventive against the complications. The objective of this study was to explore the effect of oral administration of A. angustissima methanol extract on physiological parameters of streptozotocin-induced diabetic rats. The results indicated a significant reduction in blood glucose levels, an increase in serum insulin concentration, a decrease in lipid levels and an improvement in the parameters of kidney damage by applying a concentration of 100 mg/Kg B.W. However, glucose uptake activity was not observed in the adipocyte assay. Moreover, the extract of A. angustissima displayed potential for the complementary treatment of diabetes and its complications likely due to the presence of bioactive compounds such as protocatechuic acid. This study demonstrated that methanol extract of Acacciella angustissima has an antidiabetic effect by reducing the levels of glucose, insulin and improved physiological parameters, hypolipidemic effect, oxidative stress and renal damage in diabetic rats.


2013 ◽  
Vol 4 (1) ◽  
pp. 5 ◽  
Author(s):  
AndréValle de Bairros ◽  
Fernando de Freitas ◽  
Mirna Leal ◽  
Cinthia Mazzanti ◽  
AnaPaula Moreira ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
C. O. Nwaehujor ◽  
I. I. Ezeigbo ◽  
F. C. Nwinyi

Objective. Mallotus oppositifolius(Geiseler) Müll. Arg. (Euphorbiaceae) is folklorically used to “treat” diabetic conditions in some parts of Nigeria therefore the study, to investigate the extract of the leaves for activities on hyperglycaemia, lipid peroxidation, and increased cholesterol levelsin vivoin alloxan diabetic rats as well as its potential antioxidant activityin vitro.Methods. Albino rats (240–280 g) were given an injection of 120 mg/kg body weight, i.p. of alloxan monohydrate. After 8 days, diabetic animals with elevated fasting blood glucose levels (>9 mmol/L) were considered and selected for the study.Results. Oral treatment with the extract administered every 12 h by gavage at doses of 100, 200, and 400 mg/kg of the extract to the test rats, for 14 days, resulted in a significant dose-dependent decrease in blood glucose levels from 12.82 ± 1.02 mmol/dL to 4.92 ± 2.01 mmol/dL at the highest dose of 400 mg/kg compared to the control drug and glibenclamide as well as attendant significant decline in diabetic rats employed in the study.Conclusion. The extract also showedin vitroconcentration-dependent antioxidant activity following the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric reducing assays. Findings further suggest the presence of active antidiabetic and antioxidant principles inM. oppositifoliusleaves.


2020 ◽  
Vol 11 (4) ◽  
pp. 7950-7957
Author(s):  
Pratap Reddy K ◽  
Bhaskar Nagilla ◽  
Varija K

The aim of the present study was to evaluate the protective effect of methanol garlic extract on the enzymes related with polyol pathway, advanced glycation end products, markers of oxidative stress and antioxidant status in brain of streptozotocin induced diabetic rats. Antioxidant capability of methanol extract of garlic was evaluated by 2,2-diphenyl-2-picrylhydrazyl hydrate radical and FOX (ferrous ion oxidation-xylenol orange) H2O2 scavenging test. Diabetes was induced by single i.p injection of STZ (32mg/kg per body Wt.,). Blood glucose levels and body wt, were measured on every 7th day over a period of 30 days. The diabetic rats treated with garlic extract at two doses 250mg/kg and 500mg/kg body wt., by oral administration. Diabetic rats showed significant increase in food and water intake, decrease in blood glucose levels, body weights, but could not show any recovery by garlic treatment. Garlic treatment significantly decreased aldose reductase (AR); sorbitol dehydrogenase (SD) and glutathione S-transferase (GST) enzyme activities. A decrease of malndialdehyde (MDA), Protein carbonyls (PC), Pentosidine advance oxidation protein products (AOPP), Advanced glycation end products (AGEs) was also observed. Additionally garlic administration produced a restoration of brain superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) in diabetic rats. Garlic treatment also reduced the free radical formation and progression of hyperglycemia induced diabetic complications by decreasing influx of glucose into the polyol pathway and increased activity of antioxidant enzymes. The current study reveals exerts, efficiently, an attenuating effect of methanol garlic extract exterted antihyperlgycemic, antioxidant and anti-glycating effects in a dose dependent manner in diabetic rats.


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