The Experts below are selected from a list of 9438 Experts worldwide ranked by ideXlab platform
Yueyi Deng - One of the best experts on this subject based on the ideXlab platform.
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puerarin attenuated early diabetic Kidney injury through down regulation of matrix metalloproteinase 9 in streptozotocin induced diabetic rats
PLOS ONE, 2014Co-Authors: Yifei Zhong, Xianwen Zhang, Xianfan Cai, Ke Wang, Yiping Chen, Yueyi DengAbstract:Radix puerariae, a traditional Chinese herbal medication, has been used successfully to treat patients with early stage of diabetic nephropathy. However, the underlined mechanism of this renal protective effect has not been determined. In the current study, we investigated the effects and the mechanism of puerarin in Streptozotocin (STZ)-induced diabetic rats. We treated STZ-rats with either puerarin or losartan, an angiotensin II receptor blocker, as compared to those treated with vehicle. We found that both puerarin and losartan attenuated Kidney Hypertrophy, mesangial expansion, proteinuria, and podocyte foot process effacement in STZ rats. In addition, both puerarin and losartan increased expression of podocyte slit diaphragm proteins such as nephrin and podocin. Interestingly, we found that puerarin treatment induced a more pronounced suppression of oxidative stress production and S-nitrosylation of proteins in the diabetic Kidneys as compared to losartan treatment. Furthermore, we found that matrix metalloproteinase-9 (MMP-9), which is known to be activated by oxidative stress and S-nitrosylation of proteins, was also suppressed more extensively by puerarin than losartan. In conclusion, these data provide for the first time the potential mechanism to support the use of puerarin in the treatment of early diabetic nephropathy.
Shing Jong Lin - One of the best experts on this subject based on the ideXlab platform.
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matrix metalloproteinase 9 deficiency attenuates diabetic nephropathy by modulation of podocyte functions and dedifferentiation
Kidney International, 2014Co-Authors: Po Hsun Huang, An Hang Yang, Der Cherng Tarng, Wu Chang Yang, Chih Ching Lin, Jaw Wen Chen, Geert W Schmidschonbein, Shing Jong LinAbstract:Diabetic nephropathy is characterized by excessive deposition of extracellular matrix protein and disruption of the glomerular filtration barrier. Matrix metalloproteinases (MMPs) affect the breakdown and turnover of extracellular matrix protein, suggesting that altered expression of MMPs may contribute to diabetic nephropathy. Here we used an MMP-9 gene knockout mouse model, with in vitro experiments and clinical samples, to determine the possible role of MMP-9 in diabetic nephropathy. After 6 months of streptozotocin-induced diabetes, mice developed markedly increased albuminuria, glomerular and Kidney Hypertrophy, and thickening of the glomerular basement membrane. Gelatin zymographic analysis and western blotting showed that there was enhanced MMP-9 protein production and activity in the glomeruli. However, MMP-9 knockout in diabetic mice significantly attenuated these nephropathy changes. In cultured podocytes, various cytokines related to diabetic nephropathy including TGF-β1, TNF-α, and VEGF stimulated MMP-9 secretion. Overexpression of endogenous MMP-9 induced podocyte dedifferentiation. MMP-9 also interrupted podocyte cell integrity, promoted podocyte monolayer permeability to albumin, and extracellular matrix protein synthesis. In diabetic patients, the upregulation of urinary MMP-9 concentrations occurred earlier than the onset of microalbuminuria. Thus, MMP-9 seems to play a role in the development of diabetic nephropathy.
Sadhana Sathaye - One of the best experts on this subject based on the ideXlab platform.
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renoprotective effect of diosgenin in streptozotocin induced diabetic rats
Pharmacological Reports, 2016Co-Authors: Divya M Kanchan, Gauresh Somani, Vaibhavi Peshattiwar, Aakruti Kaikini, Sadhana SathayeAbstract:Abstract Background Diabetes mellitus is a multifactorial metabolic disorder associated with genesis of diabetes related vascular diseases. Oxidative stress along with inflammation is the major causative factor leading to diabetic complications. The present study examined the protective effect of diosgenin, a steroidal saponin, in diabetes induced early Kidney injury. Methods Diabetes was induced by streptozotocin (45 mg/kg) in rats followed by treatment for 28 days with diosgenin (5, 10 and 20 mg/kg, oral). Blood glucose levels, lipid profile, serum advanced glycation end-products, biomarkers of Kidney damage like urinary protein excretion, Kidney Hypertrophy index and creatinine in serum and urine were determined. Biochemical analysis of oxidative stress parameters such as superoxide dismutase, catalase, reduced glutathione, lipid peroxidation (LPO) and myeloperoxidase level were evaluated in Kidney homogenates. Histopathological evaluation of Kidney was also studied. Results Treatment with diosgenin significantly ameliorated the altered oxidative stress levels in STZ induced diabetic rats resulting in decreased LPO and increased endogenous antioxidant levels in a dose-dependent manner. Blood glucose was significantly decreased at 20 mg/kg. The distorted levels of biomarkers suggestive of Kidney damage were significantly normalized by diosgenin providing protection to Kidneys also confirmed by histopathological studies. Decreased myeloperoxidase levels in diosgenin treatment groups revealed its anti-inflammatory activity. Conclusion The above study justifies diosgenin as a promising candidate in diabetes associated complication through its antioxidant and anti-inflammatory activity.
Archana R Juvekar - One of the best experts on this subject based on the ideXlab platform.
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attenuation of diabetic nephropathy in streptozotocin induced diabetic rats by punica granatum linn leaves extract
Journal of Traditional and Complementary Medicine, 2017Co-Authors: Snehal N Mestry, Jayesh B Dhodi, Sangita Balbhim Kumbhar, Archana R JuvekarAbstract:With an objective to develop Complementary and Alternative Medicine for the treatment of diabetic nephropathy, the present study investigated the protective effects of methanolic extract of Punica granatum leaves (MPGL) in streptozotocin-induced diabetic nephropathy. Diabetic nephropathy has become a leading cause of end stage renal failure worldwide. P. granatum, due to its anti-diabetic, anti-inflammatory and antioxidant activities may retard the progression of diabetic nephropathy. In this study, diabetes was induced by a single injection of streptozotocin (STZ, 45 mg/kg, i.p.) in rats. STZ-diabetic rats were treated with oral doses of MPGL (100, 200 and 400 mg/kg) for 8 weeks. At the end of the experimental period, body and Kidney weight and blood glucose levels were determined. Serum and urine parameters were investigated. Antioxidant enzymes and lipid peroxide levels were determined in the Kidney along with histopathological examination of the same. MPGL significantly increased body weight, lowered blood glucose levels and ameliorated Kidney Hypertrophy index in the STZ-diabetic rats. The extract also decreased the levels of creatinine, blood urea nitrogen, total cholesterol, triglycerides, advanced glycation end products and albumin in serum and urine, respectively. MPGL significantly increased the antioxidant parameters in the Kidney. Histological evaluation revealed that MPGL treated STZ-diabetic rats demonstrated reduced vacuolar degeneration of tubules; periodic acid Schiff base (PAS) positivity staining intensity in glomeruli and basement membrane thickening. Present findings provide experimental evidence that MPGL has potential antioxidant, antihyperglycemic and anti-glycation activities which might be helpful in slowing the progression of diabetic nephropathy.
David Schubert - One of the best experts on this subject based on the ideXlab platform.
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Fisetin lowers methylglyoxal dependent protein glycation and limits the complications of diabetes
PLOS ONE, 2011Co-Authors: Pamela Maher, Richard Dargusch, Jennifer Ehren, Shinichi Okada, Kumar Sharma, David SchubertAbstract:The elevated glycation of macromolecules by the reactive dicarbonyl and α-oxoaldehyde methylglyoxal (MG) has been associated with diabetes and its complications. We have identified a rare flavone, fisetin, which increases the level and activity of glyoxalase 1, the enzyme required for the removal of MG, as well as the synthesis of its essential co-factor, glutathione. It is shown that fisetin reduces two major complications of diabetes in Akita mice, a model of type 1 diabetes. Although fisetin had no effect on the elevation of blood sugar, it reduced Kidney Hypertrophy and albuminuria and maintained normal levels of locomotion in the open field test. This correlated with a reduction in proteins glycated by MG in the blood, Kidney and brain of fisetin-treated animals along with an increase in glyoxalase 1 enzyme activity and an elevation in the expression of the rate-limiting enzyme for the synthesis of glutathione, a co-factor for glyoxalase 1. The expression of the receptor for advanced glycation end products (RAGE), serum amyloid A and serum C-reactive protein, markers of protein oxidation, glycation and inflammation, were also increased in diabetic Akita mice and reduced by fisetin. It is concluded that fisetin lowers the elevation of MG-protein glycation that is associated with diabetes and ameliorates multiple complications of the disease. Therefore, fisetin or a synthetic derivative may have potential therapeutic use for the treatment of diabetic complications.
