Polydatin-loaded chitosan nanoparticles ameliorates early diabetic nephropathy by attenuating oxidative stress and inflammatory responses in streptozotocin-induced diabetic rat

AbstractWith the advances in biomedical technologies, natural products have attracted substantial public attention in the area of drug discovery. Flavonoids are a class of active natural products with a wide range of pharmacological effects that are used for the treatment of several diseases, in particular chronic metabolic diseases. Diabetic nephropathy is a complication of diabetes with a particularly complicated pathological mechanism that affects at least 30% of diabetic patients and represents a great burden on public health. A large number of studies have shown that flavonoids can alleviate diabetic nephropathy. This review systematically summarizes the use of common flavonoids for the treatment of diabetic nephropathy. We found that flavonoids play a therapeutic role in diabetic nephropathy mainly by regulating oxidative stress and inflammation. Nrf-2/GSH, ROS production, HO-1, TGF-β1 and AGEs/RAGE are involved in the process of oxidative stress regulation. Quercetin, apigenin, baicalin, luteolin, hesperidin, genistein, proanthocyanidin and eriodictyol were found to be capable of alleviating oxidative stress related to the aforementioned factors. Regarding inflammatory responses, IL-1, IL-6β, TNF-α, SIRT1, NF-κB, and TGF-β1/smad are thought to be essential. Quercetin, kaempferol, myricetin, rutin, genistein, proanthocyanidin and eriodictyol were confirmed to influence the above targets. As a result, flavonoids promote podocyte autophagy and inhibit the overactivity of RAAS by suppressing the upstream oxidative stress and inflammatory pathways, ultimately alleviating DN. The above results indicate that flavonoids are promising drugs for the treatment of diabetic nephropathy. However, due to deficiencies in the effect of flavonoids on metabolic processes and their lack of structural stability in the body, further research is required to address these issues.

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1α,25-Dihydroxyvitamin D3 prevents renal oxidative damage via the PARP1/SIRT1/NOX4 pathway in Zucker diabetic fatty rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00270.2019 ◽

2020 ◽

Vol 318 (3) ◽

pp. E343-E356

Author(s):

Dongxia Wang ◽

Yanyan Li ◽

Ning Wang ◽

Gang Luo ◽

Jun Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Oxidative Damage ◽

Sirtuin 1 ◽

Diabetic Rat ◽

Membrane Thickness ◽

Basement Membrane Thickness ◽

Zucker Diabetic Fatty Rats ◽

Zdf Rats ◽

Rat Kidneys

Diabetic nephropathy (DN) is one of the most important renal complications associated with diabetes, and the mechanisms are yet to be fully understood. To date, few studies have shown the antioxidant effects of 1α,25-dihydroxyvitamin-D3 [1,25(OH)2D3] on hyperglycemia-induced renal injury. The aim of the present study was to explore the potential mechanism by which 1,25(OH)2D3 reduced oxidative stress in diabetic rat kidneys. In this study, we established a vitamin D-deficient spontaneous diabetes model: 5–6 wk of age Zucker diabetic fatty (ZDF) rats were treated with or without 1,25(OH)2D3 for 7 wk, age-matched Zucker lean rats served as control. Results showed that ZDF rats treated with 1,25(OH)2D3 had decreased body mass, food intake, water intake, and urine volume. 1,25(OH)2D3 ameliorated urine glucose, blood glucose and abnormal glucose tolerance. Additionally, 1,25(OH)2D3 significantly lowered microalbuminuria, decreased the glomerular basement membrane thickness, and in some degree inhibited glomerular hypertrophy, mesangial expansion, and tubular dilatation. Furthermore, 1,25(OH)2D3 attenuated renal oxidative damage, as reflected by the levels of malondialdehyde, reduced glutathione, 4-hydroxynonenal, 8-hydroxy-2'-deoxyguanosine, and reactive oxygen species production, and notably inhibited poly(ADP-ribose) polymerase-1 (PARP1), activated sirtuin 1 (SIRT1), and decreased the expression of NADPH oxidase 4 (NOX4). Of interest, the abovementioned proteins could be involved in the antioxidant mechanism of 1,25(OH)2D3 in diabetic rat kidneys. Our study showed that oxidative stress might be a major contributor to DN pathogenesis and uncovered the antioxidant role of 1,25(OH)2D3 in diabetic nephropathy that was associated with the PARP1/SIRT1/ NOX4 pathway.

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Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy

Journal of Diabetes Research ◽

10.1155/2016/4626125 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 41

Author(s):

Cristina Gluhovschi ◽

Gheorghe Gluhovschi ◽

Ligia Petrica ◽

Romulus Timar ◽

Silvia Velciov ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Diabetic Nephropathy ◽

Early Diagnosis ◽

Gold Standard ◽

Tubular Injury ◽

Inflammation Markers ◽

Vascular Biomarkers ◽

Early Diabetic Nephropathy ◽

Biomarkers Of Oxidative Stress

Diabetic nephropathy (DN) is a frequent and severe complication of diabetes mellitus (DM). Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition—mainly cardiovascular ones—and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress) precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new “gold standard” biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin) are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN.

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Moderate exercise attenuates caspase-3 activity, oxidative stress, and inhibits progression of diabetic renal disease in db/db mice

AJP Renal Physiology ◽

10.1152/ajprenal.90548.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. F700-F708 ◽

Cited By ~ 65

Author(s):

S. Ghosh ◽

M. Khazaei ◽

F. Moien-Afshari ◽

L. S. Ang ◽

D. J. Granville ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Oxidative Damage ◽

Renal Disease ◽

Caspase 3 ◽

Moderate Intensity ◽

Caspase 8 ◽

Apoptotic Pathway ◽

Mitochondrial Apoptotic Pathway ◽

Early Diabetic Nephropathy

Diabetic nephropathy, the leading cause of end-stage renal disease, is characterized by a proapoptotic and prooxidative environment. The mechanisms by which lifestyle interventions, such as exercise, benefit diabetic nephropathy are unknown. We hypothesized that exercise inhibits early diabetic nephropathy via attenuation of the mitochondrial apoptotic pathway and oxidative damage. Type 2 diabetic db/db and normoglycemic wild-type mice were exercised for an hour everyday at a moderate intensity for 7 wk, following which renal function, morphology, apoptotic signaling, and oxidative stress were evaluated. Exercise reduced body weight, albuminuria, and pathological glomerular expansion in db/db mice independent of hyperglycemic status. Changes in renal morphology were also related to reduced caspase-3 (main effector caspase in renal apoptosis), caspase-8 (main initiator caspase of the “extrinsic” pathway) activities, and TNF-α expression. A role for the mitochondrial apoptotic pathway was unlikely as both caspase-9 activity (initiator caspase of this pathway) and expression of regulatory proteins such as Bax and Bcl-2 were unchanged. Kidneys from db/db mice also produced higher levels of superoxides and had greater oxidative damage concurrent with downregulation of superoxide dismutase (SOD) 1 and 3. Interestingly, although exercise also increased superoxides, there was also upregulation of multiple SODs that likely inhibited lipid (hydroperoxides) and protein (carbonyls and nitrotyrosine) oxidation in db/db kidneys. In conclusion, exercise can inhibit progression of early diabetic nephropathy independent of hyperglycemia. Reductions in caspase-3 and caspase-8 activities, with parallel improvements in SOD expression and reduced oxidative damage, could underlie the beneficial effects of exercise in diabetic kidney disease.

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EXPLORATION OF PROTECTIVE EFFECT OF HYDROALCOHOLIC EXTRACT OF ALSTONIA SCHOLARIS BARK IN STZ-INDUCED EARLY DIABETIC NEPHROPATHY MODEL IN RATS

INDIAN DRUGS ◽

10.53879/id.56.08.11482 ◽

2019 ◽

Vol 56 (08) ◽

pp. 69-78

Author(s):

D. D. Bandawane ◽

S. B Jadhav ◽

A. R. Juvekar ◽

Keyword(s):

Oxidative Stress ◽

Superoxide Dismutase ◽

Diabetic Nephropathy ◽

Reduced Glutathione ◽

Serum Insulin ◽

Fasting Blood Glucose ◽

Diabetic Rats ◽

Total Proteins ◽

Hydroalcoholic Extract ◽

Early Diabetic Nephropathy

Alstonia scholaris (fam. Apocynaceae) is an indigenous plant used traditionally for the treatment of diabetes and associated complications. However the nephroprotective potential of the plant is not scientifically evaluated. Objective of the present was to investigate renal protective activity of hydroalcoholic extract of A. scholaris bark (HEAS) in streptozotocin (STZ)-induced early diabetic nephropathy in rats and to focus on its possible mechanism of action. Experimental diabetes was induced in Wistar rats using single intraperitoneal injection of streptozotocin (65 mg/kg). Animals were divided in five groups (n=6) and treated with 150 mg/kg and 300 mg/kg HEAS for 4 weeks. At the end of study period, fasting blood glucose, blood urea nitrogen (BUN), serum creatinine, total proteins, serum albumin, serum insulin and glycosylated haemoglobin, superoxide dismutase, catalase, reduced glutathione and MDA in kidney were evaluated. Urine was analyzed for albumin, total proteins and creatinine clearance. Kidney and pancreas were subjected for histopathology. Significant decrease in fasting blood glucose, creatinine, albumin, BUN, total proteins and urinary total proteins was observed. Significant improvement in serum insulin, glycosylated Hb, oxidative stress parameters of kidney including superoxide dismutase, catalase and reduced glutathione has been observed in HEAS treated diabetic rats. Histopathology of kidney and pancreatic tissues showed structural improvement. Present study has revealed that HEAS prevented the progression of diabetic nephropathy in STZ-diabetic rats by improving the disturbed glucose homeostasis and by amelioration of renal oxidative stress.

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Comparison of the Effects of Korean Ginseng and Heat-Processed Korean Ginseng on Diabetic Oxidative Stress

The American Journal of Chinese Medicine ◽

10.1142/s0192415x08006417 ◽

2008 ◽

Vol 36 (05) ◽

pp. 989-1004 ◽

Cited By ~ 19

Author(s):

Hyun Young Kim ◽

Ki Sung Kang ◽

Noriko Yamabe ◽

Takako Yokozawa

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Renal Damage ◽

Advanced Glycation Endproducts ◽

Diabetic Rats ◽

Heat Processing ◽

Diabetic Rat ◽

Thiobarbituric Acid Reactive Substance ◽

Pathological Conditions ◽

Korean Ginseng

To investigate the effects of Korean ginseng (KG, Panax ginseng C.A. Meyer) and heat-processed Korean ginseng (H-KG) on diabetic renal damage, we used the streptozotocin-induced diabetic rat model in this study. The diabetes-induced physiological abnormalities at early-stage were attenuated by KG or H-KG administration through reducing the blood glucose level and improving renal function. The oxidative stress-induced increases in serum and renal thiobarbituric acid-reactive substance levels were significantly reduced by KG and H-KG administrations. Moreover, the protein expressions related to oxidative stress and advanced glycation endproducts were significantly reduced in diabetic rats and/or not significantly increased compared to normal rats by KG or H-KG administration. All of these beneficial effects of H-KG in diabetic rats were stronger than those of KG. Therefore, KG and H-KG may improve diabetic pathological conditions and prevent renal damage associated with diabetic nephropathy, and these protective effects of KG can be improved by heat-processing. This study provides scientific evidence that H-KG may be a potential therapeutic agent for pathological conditions associated with diabetic complications including diabetic nephropathy.

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Oleanolic acid andN-acetylcysteine ameliorate diabetic nephropathy through reduction of oxidative stress and endoplasmic reticulum stress in a type 2 diabetic rat model

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfv377 ◽

2015 ◽

Vol 31 (3) ◽

pp. 391-400 ◽

Cited By ~ 35

Author(s):

Eun Soo Lee ◽

Hong Min Kim ◽

Jeong Suk Kang ◽

Eun Young Lee ◽

Dhananjay Yadav ◽

...

Keyword(s):

Oxidative Stress ◽

Endoplasmic Reticulum ◽

Diabetic Nephropathy ◽

Endoplasmic Reticulum Stress ◽

Oleanolic Acid ◽

Rat Model ◽

Diabetic Rat ◽

Diabetic Rat Model ◽

Type 2 Diabetic

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Fenugreek Prevents the Development of STZ-Induced Diabetic Nephropathy in a Rat Model of Diabetes

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/259368 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

Yingli Jin ◽

Yan Shi ◽

Yinggang Zou ◽

Chunsheng Miao ◽

Bo Sun ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Growth Factor ◽

Rat Model ◽

Transforming Growth Factor ◽

Tissue Growth ◽

Diabetic Rat ◽

Dimethyl Formamide ◽

Interventional Treatment ◽

Morphological Alterations

The present study aims to examine the protective effect of fenugreek and the underlying mechanism against the development of diabetic nephropathy (DN) in streptozotocin- (STZ-) induced diabetic rats. A rat model of diabetes was successfully established by direct injection of STZ and then the rats were administered an interventional treatment of fenugreek. Parameters of renal function, including blood glucose, albuminuria, hemoglobin A1c (HbA1c), dimethyl formamide (DMF), blood urine nitrogen (BUN), serum creatinine (Scr), and kidney index (KI), were detected in the three groups (Con, DN, and DF). Oxidative stress was determined by the activity of antioxidase. Extracellular matrix (ECM) accumulation and other morphological alterations were evaluated by means of immunohistochemistry and electron microscope. Quantitive (q)PCR was employed to detect the mRNA expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) and protein expression was determined with western blot analysis. DN rats in the present study demonstrated a significant renal dysfunction, ECM accumulation, pathological alteration, and oxidative stress, while the symptoms were evidently reduced by fenugreek treatment. Furthermore, the upregulation of TGF-β1 and CTGF at a transcriptional and translational level in DN rats was distinctly inhibited by fenugreek. Consequently, fenugreek prevents DN development in a STZ-induced diabetic rat model.

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