scholarly journals Amelioration of neuropilin-1 and rage/matrix metalloproteinase-2 pathway-induced renal injury in diabetic rats by rosuvastatin

2021 ◽  
pp. 21-21
Author(s):  
Rabia Nabi ◽  
Sultan Alvi ◽  
Sultan Alouffi ◽  
Saif Khan ◽  
Adnan Ahmad ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Renal Injury ◽  
Reductase Activity ◽  
Renal Tissue ◽  
Diabetic Rats ◽  
Paraoxonase 1 ◽  
Matrix Metalloproteinase 2 ◽  
Altered Level ◽  
Neuropilin 1 ◽  
Coa Reductase

Advanced glycation end-products (AGEs) induce the production of reactive oxygen species (ROS) and extra cellular matrix (ECM) degradation via suppression of neuropilin-1 (NRP-1) and interaction with AGE-receptors (RAGE). This study aimed to reveal whether modulation of NRP-1 by rosuvastatin (RT) prevents AGE-induced renal injury via targeting RAGE/matrix metalloproteinase-2 (MMP-2) signaling in diabetic rats. Treatment with RT ameliorated the altered level of markers of glycemic control, renal injury, cholesterol, triglyceride (TG) and hepatic HMG-CoA reductase activity; the level of circulatory carboxymethyl-lysine (CML) and the accumulation of fluorogenic-AGEs in renal tissue was reduced; the expression of renal NRP-1, a checkpoint target, was stimulated; the transcription of RAGE, NF?B-2, TGF-?1 and MMP-2 was suppressed; the circulatory carbonyl content (CC) and paraoxonase-1 (PON-1) activity was ameliorated, and renal histopathological features were attenuated as evidenced by improved glomerular appearance, Bowman?s space and abundant podocytes in kidneys. In conclusion, RT exhibited the potential to counteract diabetes and AGE-induced renal pathologies via stimulation of NRP-1, suppression of RAGE, and of genes responsible for ECM disintegration (MMP-2) and the inflammatory response (NF?B-2).

scholarly journals Study on Association of Pentraxin 3 and Diabetic Nephropathy in a Rat Model

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xuehai Chen ◽  
Jiao Luo ◽  
Minmin Wu ◽  
Zhuo Pan ◽  
Yue Xie ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Islet Transplantation ◽  
Renal Injury ◽  
Microvascular Disease ◽  
Renal Tissue ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Tubular Injury ◽  
Clinical Progression ◽  
Renal Tubular

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. Compared with other therapies for diabetic patients, islet transplantation can effectively prevent and reverse diabetes-induced microvascular disease, such as diabetic retinopathy and nephropathy. PTX3 is the only long pentraxin that can be detected in renal tissue. In this study, we investigated the expression of PTX3 when early DN was reversed after islet transplantation.Methods. Diabetes was induced in rats by injecting streptozotocin (STZ). Twelve weeks later, the diabetic rats were divided into 2 groups: the islet transplantation group (IT) and the diabetic nephropathy group (DN). Renal injury, renal function, and the expression of PTX3 in the plasma and the kidneys were assessed with urinalysis, immunohistochemical staining, and Western blot, respectively.Results. The expression of PTX3 in the kidney was significantly decreased in the DN group but increased in the IT group because of the reversal of DN.Conclusions. Our data showed that the level of PTX3 in renal tissue is closely related to renal injury in DN. This may be used to quantify the extent of renal injury in DN, provide a potential early indicator of renal tubular injury in early DN patients, and assess DN clinical progression.

scholarly journals Inhibitory effects of some long-chain unsaturated fatty acids on mitochondrial β-oxidation. Effects of streptozotocin-induced diabetes on mitochondrial β-oxidation of polyunsaturated fatty acids

1985 ◽  
Vol 230 (2) ◽  
pp. 329-337 ◽  
Author(s):  
H Osmundsen ◽  
K Bjørnstad
Keyword(s):  
Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
Reductase Activity ◽  
Liver Mitochondria ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Inhibitory Property ◽  
Streptozotocin Induced Diabetes ◽  
Streptozotocin Diabetic Rats ◽  
Coa Reductase

Evidence showing that some unsaturated fatty acids, and in particular docosahexaenoic acid, can be powerful inhibitors of mitochondrial β-oxidation is presented. This inhibitory property is, however, also observed with the cis- and trans-isomers of the C18:1(16) acid. Hence it is probably the position of the double bond(s), and not the degree of unsaturation, which confers the inhibitory property. It is suggested that the inhibitory effect is caused by accumulation of 2,4-di- or 2,4,7-tri-enoyl-CoA esters in the mitochondrial matrix. This has previously been shown to occur with these fatty acids, in particular when the supply of NADPH was limiting 2,4-dienoyl-CoA reductase (EC 1.3.1.-) activity [Hiltunen, Osmundsen & Bremer (1983) Biochim. Biophys. Acta 752, 223-232]. Liver mitochondria from streptozotocin-diabetic rats showed an increased ability to β-oxidize 2,4-dienoyl-CoA-requiring acylcarnitines. Docosahexaenoylcarnitine was also found to be less inhibitory at lower concentrations with incubation under coupled conditions. With uncoupling conditions there was little difference between mitochondria from normal and diabetic rats in these respects. This correlates with a 5-fold stimulation of 2,4-dienoyl-CoA reductase activity found in mitochondria from streptozotocin-diabetic rats.

Matrix metalloproteinase 2 and basement membrane integrity: a unifying mechanism for progressive renal injury

2006 ◽  
Vol 20 (11) ◽  
pp. 1898-1900 ◽  
Author(s):  
Sunfa Cheng ◽  
Allan S. Pollock ◽  
Rajeev Mahimkar ◽  
Jean L. Olson ◽  
David H. Lovett ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Matrix Metalloproteinase ◽  
Renal Injury ◽  
Membrane Integrity ◽  
Matrix Metalloproteinase 2

Effect of glucose or fructose feeding on cholesterol synthesis in diabetic animals

1985 ◽  
Vol 249 (5) ◽  
pp. G634-G641 ◽  
Author(s):  
K. R. Feingold ◽  
A. H. Moser
Keyword(s):  
Cholesterol Synthesis ◽  
Reductase Activity ◽  
Active Form ◽  
Diabetic Rats ◽  
Hepatic Cholesterol ◽  
Hmg Coa Reductase ◽  
Hepatic Cholesterol Synthesis ◽  
Streptozotocin Induced Diabetes ◽  
Intestinal Hypertrophy ◽  
Coa Reductase

Previous studies have demonstrated that cholesterol synthesis is increased twofold in the small intestines of rats with streptozotocin-induced diabetes. The purpose of the present study was to determine the effect of adding glucose or fructose to standard rat chow on cholesterol synthesis in control and diabetic rats. In control rats a 25% glucose or fructose diet fed for 21 days markedly inhibited hepatic cholesterol synthesis in the liver. In contrast, in diabetic animals only fructose inhibited hepatic cholesterol synthesis. In both control and diabetic animals the addition of these simple sugars to the diet did not markedly alter extrahepatic cholesterol synthesis. The enhancement of small intestinal cholesterol synthesis observed in diabetic animals was present regardless of the dietary manipulations. Further studies demonstrated that the addition of smaller concentrations of fructose (10%) to standard rat chow decreased hepatic cholesterol synthesis in both control and diabetic rats. Similarly the addition of fructose to the diet of control and diabetics for a period as short as 2 days was also sufficient to inhibit hepatic cholesterol synthesis. In both control and diabetic animals, fructose feeding decreased hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity but did not alter the percentage of HMG-CoA reductase in the active form. Finally, the intestinal hypertrophy and stimulation of intestinal cholesterogenesis that are characteristic of streptozotocin-induced diabetes occurred when either glucose or fructose was the sole caloric source.

Lercanidipine decreases vascular matrix metalloproteinase-2 activity and protects against vascular dysfunction in diabetic rats

2008 ◽  
Vol 599 (1-3) ◽  
pp. 110-116 ◽  
Author(s):  
Marcio L.L. Martinez ◽  
Elen Rizzi ◽  
Michele M. Castro ◽  
Karla Fernandes ◽  
Lusiane M. Bendhack ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Vascular Dysfunction ◽  
Diabetic Rats ◽  
Matrix Metalloproteinase 2

Abstract 55: Involvement of Matrix Metalloproteinase-2 During the Progression of Renal Disease in Diabetic Dahl Salt-sensitive Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Tiffani Slaughter ◽  
Adrienne Paige ◽  
Fan Fan ◽  
Patrick Kyle ◽  
Aron M Geurts ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Matrix Metalloproteinase ◽  
Renal Disease ◽  
Renal Injury ◽  
Interstitial Fibrosis ◽  
Type I Diabetes ◽  
Matrix Metalloproteinase 2 ◽  
Type I ◽  
Protein Excretion ◽  
Low Salt

Recently, our laboratory reported that Dahl salt-sensitive (SS) rats develop a form of renal disease following induction of diabetes with streptozotocin (STZ) that is similar to patients with diabetic nephropathy (DN). The progression of renal injury in this model was associated with increased levels of matrix metalloproteinase-2 (MMP-2) in the renal cortex. The present study examined the role of MMP-2 during the progression of diabetes-induced renal injury by comparing the development of proteinuria and renal injury following the induction of type I diabetes in SS rats and in a MMP-2 Zinc finger KO strain of SS rats with an 8 base pair frame-shift deletion (1433-1440) in exon 7 (MMP-2 ZN KO strain). The glomerular expression of MMP-2 protein was non-detectable in the MMP-2 ZN KO strain compared to SS rats fed a low salt (LS) diet. We next performed studies using 9 week-old SS and MMP-2 ZN KO rats treated with either vehicle or (2) STZ, 50 mg/kg (i.p.) to induce diabetes and fed the rats a low salt (LS) diet containing 0.4% NaCl to minimize the development of hypertension. At 18 weeks of age, protein excretion increased to 303±39 mg/day in STZ-treated SS rats (n=7) versus 112±12 mg/day in vehicle treated rats. Protein excretion only increased to 150±23 mg/day in the STZ-treated MMP-2 ZN KO strain (n=7). Blood pressure was not significantly altered and averaged 109±4 mmHg in vehicle and STZ-treated SS rats versus 108±4 mmHg in the STZ-treated MMP2-ZN KO animals. STZ-treated SS rats exhibited marked glomerular injury and extensive renal fibrosis. The degree of glomerulosclerosis and renal interstitial fibrosis was significantly reduced in the kidneys of the MMP-2 ZN KO strain. These data indicate that the progression of diabetes-induced renal injury in STZ-SS rats is associated with upregulation of the expression and activity of MMP-2 and that KO of MMP-2 gene function markedly reduces the development of proteinuria and renal injury in this model of type I diabetic nephropathy. These results also suggest that selective MMP inhibitors may be useful to prevent the development and/or progression of chronic kidney disease in the millions of patients suffering from diabetes.

scholarly journals Protective Effect of Coptis chinensis Polysaccharide Against Renal Injury by Suppressing Oxidative Stress and Inflammation in Diabetic Rats

2019 ◽  
Vol 14 (9) ◽  
pp. 1934578X1986099
Author(s):  
Shuang Jiang ◽  
Yong Tang ◽  
Yang Bao ◽  
Xin Su ◽  
Kexin Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Renal Injury ◽  
Renal Tissue ◽  
Diabetic Rats ◽  
The Body ◽  
Antidiabetic Activity ◽  
Coptis Chinensis ◽  
Tyrosine Kinase 2 ◽  
Underlying Mechanisms

Our previous studies confirmed that Coptis chinensis polysaccharide (CCPW) had a good antidiabetic activity and could improve insulin resistance. However, whether CCPW has a protective effect against the renal injury caused by diabetes has not been reported. In this study, the protective effect of CCPW against the renal injury of diabetic rats and its underlying mechanisms were investigated. The results showed that in CCPW-treated groups, the body mass of rats increased significantly, while the ratio of kidney weight to body weight decreased significantly; the 24-hour urine protein and the serum BUN and serum creatinine (Scr) levels decreased significantly, and pathological changes of the renal tissue were improved; superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities in the renal tissue were significantly higher, and malondialdehyde (MDA) contents in the renal tissue, and tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and hypersensitive c-reactive protein (hs-CRP) levels in the serum were significantly lower; the expressions of phosphorylated tyrosine kinase 2 (p-JAK2) and activators of transcription 3 (p-STAT3) decreased significantly. The results indicate that CCPW should have a protective effect against the renal injury in diabetic rats, which may be associated with its inhibition on oxidative stress and inflammation.

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