scholarly journals Tinospora cordifoliaconsumption ameliorates changes in kidney chondroitin sulphate/dermatan sulphate in diabetic rats

2012 ◽  
Vol 1 ◽  
Author(s):  
Darukeshwara Joladarashi ◽  
Nandini D. Chilkunda ◽  
Paramahans V. Salimath
Keyword(s):  
Type Iv Collagen ◽  
Chondroitin Sulphate ◽  
Rat Kidney ◽  
Apparent Molecular Weight ◽  
Diabetic Rats ◽  
Tinospora Cordifolia ◽  
Diabetic Rat ◽  
Composition Analysis ◽  
Dermatan Sulphate ◽  
Type Iv

AbstractDiabetes is known to alter kidney extracellular matrix (ECM) components. Chondroitin sulphate (CS)/dermatan sulphate (DS), an ECM component, which plays an essential role in kidney is altered during diabetes. The focus of this study has been to examine the effect ofTinospora cordifolia(TC) consumption, a potent plant widely used to treat diabetes, on kidney CS/DS. Experimentally induced diabetic rats were fed with diet containingTCat 2·5 and 5 % levels and the effect of it on kidney CS/DS was examined. The CS/DS content and CS:heparan sulphate ratio which was decreased during diabetic condition were ameliorated inTC-fed groups. Disaccharide composition analysis of CS/DS by HPLC showed that decreases in ‘E’ units and degree of sulphation were modulated in 5 %TC-fed groups. Apparent molecular weight of purified CS/DS from the control rat kidney was found to be 38 kDa which was decreased to 29 kDa in diabetic rat kidney. Rats in 5 %TC-fed groups showed chain length of 38 kDa akin to control rats. Expression of chondroitin 4-O-sulfotransferase-1, dermatan 4-O-sulfotransferase-1 andN-acetylgalactosamine 4 sulphate 6-O-sulfotransferase, enzymes involved in the synthesis of ‘E’ units which was reduced during diabetic condition, was significantly contained in the 5 %TC-fed group. Purified CS/DS from 5 %TC-fed group was able to bind higher amounts of ECM components, namely type IV collagen and laminin, when compared with untreated diabetic rats. The present results demonstrate that consumption of a diet containingTCat the 5 % level modulates changes in kidney CS/DS which were due to diabetes.

scholarly journals Glomerular Basement Membrane Selective Permeability in Short-term Streptozotocin-induced Diabetic Rats

2000 ◽  
Vol 1 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Michele Doucet ◽  
Irene Londoño ◽  
Amparo Gómez-Pascual ◽  
Moise Bendayan
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Type Iv Collagen ◽  
Serum Proteins ◽  
Diabetic Rats ◽  
Glomerular Permeability ◽  
Structural Alterations ◽  
Early Stages ◽  
Type Iv ◽  
Basement Membrane Thickening

In diabetes, the glomerular basement membrane undergoes thickening and structural alterations with loss of glomerular permselectivity properties. However, the onset of the alterations at early phases of diabetes is unclear. Aiming to determine the functional and structural alterations of the glomerular wall in the early stages of diabetes, we have studied the distribution of endogenous circulating albumin and type IV collagen in the glomerular basement membrane, using the immunocytochemical approach. The streptozotocin-injected hyperglycemic rat was our animal model. Renal tissues were examined after 10 days, 2, 4 and 6 months of hyperglycemia. Upon immunogold labelings, changes in the glomerular permeability to endogenous albumin were found altered as early as upon ten days of hyperglycemia. In contrast, no structural modifications were detected at this time point. Indeed, glomerular basement membrane thickening and an altered type IV collagen labeling distribution were only observed after four months of hyperglycemia, suggesting that functional alterations take place early in diabetes prior to any structural modification. In order to evaluate the reversibility of the glomerular alterations, two-month-old diabetic animals were treated with insulin. These animals showed a significant restoring of their glomerular permselectivity. Our results suggest a link between glycemic levels and alteration of glomerular permeability in early stages of diabetes, probably through high levels of glycated serum proteins.

scholarly journals Effects of experimental nephrosis on basement-membrane components and enzymes of collagen biosynthesis in rat kidney

1985 ◽  
Vol 226 (1) ◽  
pp. 243-250 ◽  
Author(s):  
A Jukkola ◽  
J Risteli ◽  
H Autio-Harmainen ◽  
L Risteli
Keyword(s):  
Membrane Proteins ◽  
Basement Membrane ◽  
Indirect Immunofluorescence ◽  
Type Iv Collagen ◽  
Rat Kidney ◽  
Kidney Tissue ◽  
Kidney Cortex ◽  
Collagen Biosynthesis ◽  
Type Iv ◽  
Basement Membrane Proteins

The aim of the present study was to find out whether the basement-membrane proteins laminin and type IV collagen are involved in the development of aminonucleoside-induced nephrosis. These proteins were measured by specific radioimmunoassays in serum, urine and kidney-cortex samples, and they were localized in the glomeruli by indirect immunofluorescence. Nephrosis was induced in rats with a single intraperitoneal injection of puromycin aminonucleoside. Serum laminin concentrations, detected by a radioimmunoassay for the P2 domain of the protein, increased to reach a maximum at days 5-7, and they remained elevated until at least day 14. The increase preceded the development of proteinuria, suggesting a role for laminin in glomerular function. Concomitant with proteinuria, increasing amounts of laminin antigenicity were also found in the urine. The size of the laminin antigen in serum was estimated by gel filtration, and the serum forms were found to contain both the P1 and the P2 regions of the intact laminin molecule. On the other hand, there were no changes in the serum or urinary concentrations of type-IV-collagen-derived antigens, as detected by a radioimmunoassay for the 7S collagen domain of this protein. The total content of laminin in kidney cortex, measured after digestion of the tissue with trypsin and collagenase, was, at day 9, still comparable with normal values, and the distribution of both basement-membrane proteins in the glomeruli, studied by indirect immunofluorescence, was similar to that in the controls. The tissue damage induced by aminonucleoside, however, seems to stimulate collagen biosynthesis, as the activities of prolyl 4-hydroxylase, lysyl hydroxylase and galactosylhydroxylysyl glucosyltransferase in kidney tissue increased significantly, with maxima at days 8-10.

Ethyl pyruvate ameliorates albuminuria and glomerular injury in the animal model of diabetic nephropathy

2012 ◽  
Vol 302 (5) ◽  
pp. F606-F613 ◽  
Author(s):  
Kyung Don Ju ◽  
Eun Kyoung Shin ◽  
Eun Jin Cho ◽  
Hyun Bae Yoon ◽  
Hyo Sang Kim ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Nadph Oxidase ◽  
Type Iv Collagen ◽  
Transforming Growth Factor ◽  
Ethyl Pyruvate ◽  
Reactive Oxygen Species Generation ◽  
Diabetic Rats ◽  
Protective Mechanism ◽  
Type Iv

Pyruvate is an endogenous antioxidant and anti-inflammatory substance. The present study was implemented to investigate the protective effect of ethyl pyruvate (EP) against the development and progression of diabetic nephropathy in an in vivo and in vitro model. Diabetic rats were prepared by injecting streptozotocin (65 mg/kg). Those that developed diabetes after 72 h were treated with EP (40 mg/kg) intraperitoneally. Diabetic rats without pyruvate treatment and nondiabetic rats were used for control. As an in vitro experiment, rat mesangial cells cultured primarily from Sprague-Dawley rats were treated in high-glucose (HG; 50 mM) or normal-glucose (NG; 5 mM) conditions and with or without pyruvate. Pyruvate-treated diabetic rats exhibited decreased albuminuria and attenuated NADPH-dependent reactive oxygen species generation. Immunohistochemistry showed reduced laminin, type IV collagen, and fibronectin deposition in the glomeruli compared with nontreated diabetic rats. Parallel changes were shown in tissue mRNA and protein expression levels of monocyte chemoattractant protein-1, transforming growth factor-β1, laminin, fibronectin, and type IV collagen in the kidney. Concordantly, protective effects were also exhibited in the mesangial cell culture system. These findings suggest that pyruvate protects against kidney injury via NADPH oxidase inhibition. The present study established that activation of NADPH oxidase plays a crucial role in diabetes-induced oxidative stress, glomerular hypertrophy, and ECM molecule expression. Pyruvate exhibited a renoprotective effect in the progression of experimental diabetic nephropathy. Future research is warranted to investigate the protective mechanism of pyruvate more specifically in relation to NADPH oxidase in diabetic nephropathy.

scholarly journals Transforming growth factor-beta2 antibody attenuates fibrosis in the experimental diabetic rat kidney

2001 ◽  
Vol 170 (3) ◽  
pp. 647-651 ◽  
Author(s):  
C Hill ◽  
A Flyvbjerg ◽  
R Rasch ◽  
M Bak ◽  
A Logan
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Western Blotting ◽  
Transforming Growth Factor ◽  
Rat Kidney ◽  
Human Monoclonal Antibody ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Diabetic Kidney ◽  
In The Diabetic Kidney

Diabetic nephropathy is characterised by an increase in glomerular and tubular fibrosis that compromises kidney function. The transforming growth factor-betas (TGF-betas) have been shown to play a major role in fibrosis and we have shown that TGF-beta2, in particular, increases co-ordinately with fibrogenesis in the diabetic kidney. The aim of this study was to investigate the changes in expression of extracellular matrix molecules in the diabetic kidney, with and without systemic administration of a recombinant human monoclonal antibody to TGF-beta2. Streptozotocin-induced diabetic rats were split into two groups. The first were treated with 5 mg/kg irrelevant control IgG4 (placebo) and the second treated with 5 mg/kg isoform-specific recombinant monoclonal anti-TGF-beta2 IgG4 (termed CAT-152) systemically every second day for 14 days. A further group of six non-diabetic rats was also used as a control. Various biological parameters were measured daily throughout the experimental period, and on termination of the experiment at 14 days Western blotting was performed on kidney cortices for procollagen-I C-propeptide, which is an indicator of the rate of collagen-I synthesis within the kidney. In the placebo-treated diabetic rats, blood glucose, food consumption, urinary albumin excretion (UAE) and kidney weights were all significantly higher than in the non-diabetic group (P<0.05, n=24, by ANOVA). In the anti-TGF-beta2-treated diabetic rats, kidney weights and UAE levels were decreased when compared with those in placebo-treated diabetics. Western blotting for the procollagen-I C-propeptide in kidney cortices showed a significant increase in levels in placebo-treated diabetic rats compared with non-diabetic controls over the 14 day diabetic period, indicating initiation of fibrogenesis. By contrast, in anti-TGF-beta2-treated diabetic rats, levels of the propeptide remained at non-diabetic levels. In summary, a significant suppression of kidney fibrosis was seen in anti-TGF-beta2-treated diabetic rats, compared with placebo-treated diabetic rats. We conclude that systemic delivery of CAT-152, a neutralising anti-TGF-beta2 antibody, during the acute stages of diabetic nephropathy reduces the rate of pathogenic fibrosis in the kidney.

Deficient renal 20-HETE release in the diabetic rat is not the result of oxidative stress

2008 ◽  
Vol 294 (5) ◽  
pp. H2305-H2312 ◽  
Author(s):  
Yu-Jung Chen ◽  
Jing Li ◽  
John Quilley
Keyword(s):  
Oxidative Stress ◽  
Aldose Reductase ◽  
Reductase Activity ◽  
Rat Kidney ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Glucose Levels ◽  
Nitric Oxide Formation ◽  
Streptozotocin Induced Diabetes ◽  
And Control

We confirmed that release of 20-hydroxyeicosatetraenoic acid (20-HETE) from the isolated perfused kidney of diabetic rats is greatly reduced compared with age-matched control rats. The present studies were undertaken to examine potential mechanisms for the deficit in renal 20-HETE in rats with streptozotocin-induced diabetes of 3–4 wk duration. A role for oxidative stress was excluded, inasmuch as treatment of diabetic rats with tempol, an SOD mimetic, for 4 wk did not affect the renal release of 20-HETE. Similarly, chronic inhibition of nitric oxide formation with nitro-l-arginine methyl ester or aldose reductase with zopolrestat failed to alter the release of 20-HETE from the diabetic rat kidney. Inasmuch as 20-HETE may be metabolized by cyclooxygenase (COX), the expression/activity of which is increased in diabetes, we included indomethacin in the perfusate of the isolated kidney to inhibit COX but found no effect on 20-HETE release. Diabetic rats were treated for 3 wk with fenofibrate to increase expression of cytochrome P-450 (CYP4A) in an attempt to find an intervention that would restore release of 20-HETE from the diabetic rat kidney. However, fenofibrate reduced 20-HETE release in diabetic and control rat kidneys but increased expression of CYP4A. Only insulin treatment of diabetic rats for 2 wk to reverse the hyperglycemia and maintain blood glucose levels at <200 mg/dl reversed the renal deficit in 20-HETE. We conclude that oxidative stress, increased aldose reductase activity, or increased COX activity does not contribute to the renal deficit of 20-HETE in diabetes, which may be directly related to insulin deficiency.

Effects ofSpirulina platensison lipid peroxidation, antioxidant defenses, and tissue damage in kidney of alloxan-induced diabetic rats

2018 ◽  
Vol 43 (4) ◽  
pp. 345-354 ◽  
Author(s):  
Manel Gargouri ◽  
Houda Hamed ◽  
Amel Akrouti ◽  
Xavier Dauvergne ◽  
Christian Magné ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Rat Kidney ◽  
Histological Study ◽  
Diabetic Rats ◽  
Antioxidant Defenses ◽  
Diabetic Rat ◽  
Antioxidant Enzyme Activities ◽  
Chronic Hyperglycemia ◽  
And Oxidative Stress

Chronic hyperglycemia in diabetes causes free radicals overproduction, which contributes to the development of diabetic nephropathy. In modern medicine, no satisfactory therapy is available to cure diabetes mellitus. In that context, we investigated the potential therapeutic action of spirulina-enriched diet on renal impairment and oxidative stress in diabetic rats. Diabetes was induced by a single subcutaneous injection of alloxan (120 mg·kg−1) in rats. Following alloxan treatment, male Wistar rats were fed daily with 5% spirulina-enriched diet or treated with insulin (0.5 IU·rat−1) for 3 weeks. Diabetes was associated with hyperglycemia, increase in renal oxidative parameters (lipid peroxidation, thiobarbituric-acid reactive substances, protein carbonyl and advanced oxidation protein products levels, changes in antioxidant enzyme activities), and nephropathology markers. The renal injury induced by alloxan was confirmed by histological study of the diabetic rat kidney. Treatment with spirulina or insulin significantly ameliorated renal dysfunction by reducing oxidative stress, while rats recovered normal kidney histology. Overall, this study indicates that spirulina is efficient in inhibiting hyperglycemia and oxidative stress induced by diabetes, and suggests that the administration of this alga may be helpful in the prevention of diabetic complications. This amelioration was even more pronounced than that caused by insulin injection.

scholarly journals Influence of hypertension on serum concentration of type IV collagen antigens in streptozotocin-diabetic and non-diabetic rats

Diabetologia ◽  
1987 ◽  
Vol 30 (5) ◽  
pp. 344-347 ◽  
Author(s):  
C. Hasslacher ◽  
D. Brocks ◽  
J. Mann ◽  
G. Mall ◽  
R. Waldherr
Keyword(s):  
Serum Concentration ◽  
Type Iv Collagen ◽  
Diabetic Rats ◽  
Type Iv

scholarly journals Alterations in the immunoreactivity of laminin, type IV collagen and α3β1 integrin in diabetic rat ovarian follicles

2020 ◽  
Vol 121 (05) ◽  
pp. 340-347
Author(s):  
A. B. Yildirim ◽  
D. Karabulut ◽  
E. Ozturk ◽  
E. Kaymak ◽  
B. Yalcin ◽  
...  
Keyword(s):  
Type Iv Collagen ◽  
Ovarian Follicles ◽  
Diabetic Rat ◽  
Α3β1 Integrin ◽  
Type Iv
Sign in / Sign up

Export Citation Format

Share Document