Oxidative and Nitrosative Stress and Progression of Diabetic Nephropathy in Type 2 Diabetes

Fujii, Hideki; Kono, Keiji; Nakai, Kentaro; Goto, Shunsuke; Komaba, Hirotaka; Hamada, Y.; Shinohara, Masami; Kitazawa, Riko; Kitazawa, Sohei; Fukagawa, Masafumi

doi:10.1159/000297290

Cited by 47 publications

(45 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This depletion can be partially explained by the overexpression of the NADPH oxidase in kidneys and subsequent free radical damage in diabetic nephropathy [56], since impaired function of NADPH oxidase has been suggested to have a central role on activation of other oxidative stress enzymes [57]. It has been found that DNA oxidation and nitrosative stress with excessive production of nitric oxide and peroxynitrite were implicated in progression of chronic diabetic nephropathy [58]. It has been suggested that bilirubin and biliverdin can afford protection against diabetic nephropathy by blocking NADPH oxidase [59].…”

Section: Hyperglycemia As the Great Villain In Diabetes Mellitus: Indmentioning

confidence: 99%

Antioxidant defenses in diabetes mellitus: a clinical and molecular approach

Ferrari¹

2017

Integr Obesity Diabetes

View full text Add to dashboard Cite

Oxidative and nitrosative stress reactions are implicated in cell and organ damage due to diabetes mellitus. In both type 1 and type 2 DM there is a massive oxidative and nitrosative stresses which have been associated with intensive changes on both antioxidant enzyme systems (SOD, CAT, GPx, GSH) and total antioxidant capacity (TAC) causing peroxidative damage to lipids, proteins, nucleic acids and carbohydrates which can be used as DM biomarkers. Molecular pathophysiology of diabetes mellitus envolves induction of the the NFkB and p38-MAPK cell signaling pathways by Rac, TNF-α, TLR4, decrease of antioxidant defenses, and direct mitochondrial damage. Knowledge of molecular pathways is essential for research of newer preventive and therapeutic approaches in diabetes mellitus complications (atherosclerosis, myocardial damage, endothelial dysfunction, and renal failure).urine, feces, tissue sample), vegetable or fruit extract or even foods or pharmaceuticals [14][15][16].This article review and update the clinical, cellular, and molecular knowledge of free radicals and antioxidant defenses in diabetes mellitus. Ethiopathogenesis of diabetes mellitus I and IIDiabetes mellitus has been conceptualized as a group of metabolic disorders characterized by hyperglicemia as a result of insulin secretion failure and/or lacking of insulin action on target cells. The chronic diabetic hyperglicemic state has been related to long-term organ damage especially to the heart, endothelium and blood vessels, nerves, kidney, and eyes [17][18][19].

show abstract

Section: Hyperglycemia As the Great Villain In Diabetes Mellitus: Indmentioning

confidence: 99%

Antioxidant defenses in diabetes mellitus: a clinical and molecular approach

Ferrari¹

2017

Integr Obesity Diabetes

View full text Add to dashboard Cite

show abstract

“…Thus, SDT rats will be a useful model for investigating diabetic nephropathy and suitable for preclinical drug efficacy studies. However, podocyte injury in the early stages has not been sufficiently studied in SDT rat glomeruli (Ohta et al 2007, Fujii et al 2010, Kim et al 2012.…”

Section: Introductionmentioning

confidence: 99%

Automated image analysis of a glomerular injury marker desmin in spontaneously diabetic Torii rats treated with losartan

Kakimoto¹,

Okada²,

Hirohashi³

et al. 2014

Journal of Endocrinology

View full text Add to dashboard Cite

Diabetic nephropathy is a major complication in diabetes and a leading cause of end-stage renal failure. Glomerular podocytes are functionally and structurally injured early in diabetic nephropathy. A non-obese type 2 diabetes model, the spontaneously diabetic Torii (SDT) rat, is of increasing preclinical interest because of its pathophysiological similarities to human type 2 diabetic complications including diabetic nephropathy. However, podocyte injury in SDT rat glomeruli and the effect of angiotensin II receptor blocker treatment in the early stage have not been reported in detail. Therefore, we have evaluated early stages of glomerular podocyte damage and the beneficial effect of early treatment with losartan in SDT rats using desmin as a sensitive podocyte injury marker. Moreover, we have developed an automated, computational glomerulus recognition method and illustrated its specific application for quantitatively studying glomerular desmin immunoreactivity. This state-ofthe-art method enabled automatic recognition and quantification of glomerular desminpositive areas, eliminating the need to laboriously trace glomerulus borders by hand. The image analysis method not only enabled assessment of a large number of glomeruli, but also clearly demonstrated that glomerular injury was more severe in the juxtamedullary region than in the superficial cortex region. This applied not only in SDT rat diabetic nephropathy but also in puromycin aminonucleoside-induced nephropathy, which was also studied. The proposed glomerulus image analysis method combined with desmin immunohistochemistry should facilitate evaluations in preclinical drug efficacy studies as well as elucidation of the pathophysiology of diabetic nephropathy.

show abstract

“…It is an inbred rat strain established from the Sprague-Dawley rat by Shinohara, who is affiliated with the Research Laboratories of Torii Pharmaceutical Co., Ltd., Japan [1,2]. As a result of chronic severe hyperglycemia, SDT rats develop diabetic retinopathy [1][2][3][4][5][6][7][8][9][10], diabetic peripheral neuropathy [8,9] and diabetic nephropathy [11,12]. It has been reported that male SDT rats begin showing pancreatic islet histopathology including hemorrhage in the pancreatic islets at 8-10 weeks of age, and inflammatory cell infiltration with fibroblasts infiltrating the pancreatic islets by 16 weeks of age [1,2,13].…”

Section: Introductionmentioning

confidence: 99%

Effect of Oophorectomy and Estrogen Administration on Diabetic Pathogenesis in Female Spontaneously Diabetic Torii Rats

Shinohara¹,

Oikawa²,

Sato³

et al. 2011

TODIAJ

Self Cite

View full text Add to dashboard Cite

In order to examine the effect of sex hormones on diabetic pathogenesis in female Spontaneously Diabetic Torii (SDT) rats, we performed oophorectomy on female SDT rats, administered female hormones after the oophorectomy, and measured body weight changes, plasma glucose concentration, and pancreatic histopathology. At 26 weeks of age, the body weight was significantly heavier in the oophorectomized group and significantly lighter in the estradiol benzoate (EB) administration group than in the sham-operated control group. Although glucose concentration did not significantly change in the oophorectomized group, it was significantly lower in the EB administration group than in both control and the oophorectomized group. Severe histopathological change was observed in the oophoretomized group but not in the EB administration group. Thus, EB blocked weight gain and pancreatic islet change that was induced by oophoretomy and it also lowered glucose concentration. These results suggest that estrogen plays a preventive role for diabetic pathogenesis in female SDT rats.

show abstract

Oxidative and Nitrosative Stress and Progression of Diabetic Nephropathy in Type 2 Diabetes

Cited by 47 publications

References 81 publications

Antioxidant defenses in diabetes mellitus: a clinical and molecular approach

Antioxidant defenses in diabetes mellitus: a clinical and molecular approach

Automated image analysis of a glomerular injury marker desmin in spontaneously diabetic Torii rats treated with losartan

Effect of Oophorectomy and Estrogen Administration on Diabetic Pathogenesis in Female Spontaneously Diabetic Torii Rats

Contact Info

Product

Resources

About