Hypertension aggravates glomerular dysfunction with oxidative stress in a rat model of diabetic nephropathy

Tomohiro, Tadahisa; Kumai, Toshio; Sato, Takeo; Takeba, Yuko; Kobayashi, Shinichi; Kimura, Kenjiro

doi:10.1016/j.lfs.2006.11.054

Cited by 37 publications

(28 citation statements)

References 44 publications

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“…PGFF significantly (p50.01) normalized these alterations and may thus act by decreasing gluconeogenesis. A marked increase in kidney weight as observed in our study may be due to hypertrophy caused by early diabetic nephropathy (Tomohiro et al, 2007). Our results in the present investigation showed significant decrease in the kidney weight to body weight ratio in PGFFtreated STZ diabetic rats which confirms renal protective effect of PGFF thereby controlling kidney hypertrophy.…”

Section: Body Weight (G)supporting

confidence: 83%

Flavonoid rich fraction ofPunica granatumimproves early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals

Ankita

Deepti

Nilam

2014

Pharmaceutical Biology

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Context: Different parts of Punica granatum Linn. (Punicaceae) are traditionally used as renal protective agents in the Indian system of medicine. However, there is paucity of information regarding its role in diabetic nephropathy. Objective: The present study investigates the nephroprotective potential of flavonoid-rich fraction of P. granatum leaves in streptozotocin (STZ)-induced early diabetic nephropathy in experimental animals. Materials and methods: Experimental diabetic nephropathy was induced in Wistar rats by single intraperitonial injection of STZ (65 mg/kg) dissolved in ice cold citrophosphate buffer (pH 4.3). After induction rats were divided into five groups (6 normal; 24 diabetic) and administered with glibenclamide (5 mg/kg) and three dose levels of flavonoid-rich fraction of P. granatum leaves (PGFF), i.e. 50, 100, and 200 mg/kg body weight/day for 28 d. Fasting blood glucose, lipid profile, serum albumin, serum total protein, serum creatinine, blood urea nitrogen (BUN) glycosylated hemoglobin, and biomarkers of kidney oxidative stress were assessed at the end of the treatment period. Urine was analyzed for the measurement of total protein, albumin, and creatinine clearance. Kidney sections were subjected to histopathological study. Results: Daily oral administration of variable dose levels of PGFF for 28 d normalized various biochemical, metabolic, and histopathological changes in the diabetic rats. PGFF significantly (p50.01 and p50.05) improved the glycemic status and renal function in diabetic rats as compared with diabetic control rats. Discussion and conclusion: The results of our study thus prove the protective effect of PGFF in early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals.

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Section: Body Weight (G)supporting

confidence: 83%

Flavonoid rich fraction ofPunica granatumimproves early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals

Ankita

Deepti

Nilam

2014

Pharmaceutical Biology

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“…It contributed to the improvement of renal function and proteinuria. It is also known that there is a strong epidemiological connection between hypertension in diabetes and adverse outcomes in diabetes, and the control of blood pressure represents a key component for the prevention and management of DN [34, 35]. …”

Section: Discussionmentioning

confidence: 99%

Grape Seed Proanthocyanidins Ameliorate Diabetic Nephropathy via Modulation of Levels of AGE, RAGE and CTGF

Xiao²,

Gao³

et al. 2009

Nephron Exp Nephrol

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Background: Diabetic nephropathy (DN) is the most common cause of end-stage renal failure. Grape seed proanthocyanidin extracts (GSPE) are powerful antioxidants. However, the role of GSPE on advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE) and expression of connective tissue growth factor (CTGF) in DN has not been elucidated. Using streptozotocin-induced diabetic rats, we evaluated the effects of GSPE in DN. Methods: Wistar rats were induced into diabetes using streptozotocin injections and diabetic rats were treated with GSPE (dosage: 500 mg·kg^–1·day^–1) for 24 weeks. The renal pathological changes were examined with PAS staining and electron microscope. The mRNA and protein expression of RAGE and CTGF in kidney were detected by RT-PCR, Western blot and immunohistochemical staining. Results: Treated animals showed reduction in serum AGEs (p < 0.01), proteinuria (p < 0.01) and systolic blood pressure (p < 0.01). GSPE reduced the expression of RAGE (p < 0.01) and CTGF (p < 0.01) in the kidney, which were contributing to reversal of extracellular matrix accumulation in DN. Conclusion: Our results suggest that GSPE hold substantial promise for the treatment of DN. GSPE can decrease proteinuria, attenuating the progression of nephropathy in diabetic rats. Renoprotective effects of GSPE are correlated with suppression on AGEs/RAGE axis, downregulating expression of CTGF.

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“…Oxidative stress mechanisms are involved in the pathogenesis of diabetic nephropathy; however, detailed mechanisms of ROS regulation are beginning to emerge [208,[221][222][223][224][225][226][229][230][231] . The expression of ␣ -CAT and Mn SOD proteins was significantly decreased in isolated glomeruli in the Wistar fatty rats (a type 2 diabetes mellitus model) fed high salt diet [223] . Wu et al [224] studied the mechanism with which mycophenolate mofetil attenuate renal inflammation and glomerular injury in a model of diabetes and have concluded that mycophenolate mofetil treatment ameliorates early renal injury via the inhibition of oxidative stress and overexpression of ICAM-1, MCP-1 and TGF-␤ 1 in renal tissue in diabetic rats.…”

Section: Diabetes Oxidative Stress and Antioxidantsmentioning

confidence: 99%

Free Radicals, Antioxidants and Diabetes: Embryopathy, Retinopathy, Neuropathy, Nephropathy and Cardiovascular Complications

et al. 2006

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The metabolic disturbances in the insulin-dependent diabetes mellitus or type 1 and noninsulin-dependent diabetes mellitus or type 2 are associated with a number of complications including cardiovascular diseases, nephropathy, neuropathy, retinopathy leading to blindness and embryopathy or congenital malformations. Maternal diabetes is associated with a high incidence of congenital malformations and fetal abortions. Heart and kidney anomalies, along with central nervous system defects are frequent manifestations of a maternal diabetic environment. Glycation products from excess glucose can chemically modify DNA causing mutations and complex DNA rearrangements. Therefore, DNA damage in fetal tissues as a result of maternal diabetes may reflect a level of genomic injury sufficient to affect embryonic development. The formation of advanced glycation end products can accelerate vascular occlusion by quenching the vasodilating agent nitric oxide. Interaction with high-affinity receptors located on monocytes and macrophages can enhance the production of free radicals and reactive oxygen/nitrogen species, the secretion of tumor necrosis factor-α, interleukin-1 and insulin-like growth factor 1 which can proliferate endothelial, mesangial and smooth muscle cells and hence contribute significantly to the pathogenesis of cardiovascular complications. Retinopathy is characterized by increased vascular permeability, by vascular closure, together with the growth of new blood vessels on the retina and posterior surface of the vitreous. Reactive oxygen species are involved in decreased retinal blood flow, increased vascular permeability and disruption of blood-retinal barrier. The involvement of oxidative stress in the pathology of diabetes from its associated cardiovascular dysfunctions, nephropathy, neuropathy, retinopathy (leading to blindness) and embryopathy or congenital malformations, suggests that potential management of diabetes could benefit from use of dietary biofactors in medicinal and food plants. There is therefore a requirement for research to focus on the molecular mechanisms of action of extracts and/or the biofactors flavonoids, proanthocyanidins, alkaloids, etc. derived from these plants.

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Hypertension aggravates glomerular dysfunction with oxidative stress in a rat model of diabetic nephropathy

Cited by 37 publications

References 44 publications

Flavonoid rich fraction ofPunica granatumimproves early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals

Flavonoid rich fraction ofPunica granatumimproves early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals

Grape Seed Proanthocyanidins Ameliorate Diabetic Nephropathy via Modulation of Levels of AGE, RAGE and CTGF

Free Radicals, Antioxidants and Diabetes: Embryopathy, Retinopathy, Neuropathy, Nephropathy and Cardiovascular Complications

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