Spironolactone prevents early renal injury in streptozotocin-induced diabetic rats

Fujisawa, Genro; Okada, Koji; Muto, Shigeaki; Fujita, Nobuya; Itabashi, Naoki; Kusano, Eiji; Ishibashi, Shun

doi:10.1111/j.1523-1755.2004.00913.x

Cited by 166 publications

(154 citation statements)

References 56 publications

(54 reference statements)

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“…43,44 Results obtained in CCD from rats under low-Na diet and evidence obtained in cultured nonclassical aldosterone-responsive proximal tubular cells 45 or glomerular mesangial cells 12 strongly suggest that aldosterone may induce or enhance tubulointerstitial and glomerular BASIC RESEARCH www.jasn.org inflammation and fibrosis via NF-B activation. Along with our results, these observations provide a rationale for the beneficial effects of administration of MR antagonists in both experimental [45][46][47] and human chronic kidney disease. 48 Independent from this suspected role in chronic renal disease progression, activation of NF-B by aldosterone may play a role in controlled sodium and water reabsorption by the CD.…”

Section: Discussionsupporting

confidence: 77%

Aldosterone Activates NF-κB in the Collecting Duct

Leroy

Seigneux²,

Agassiz³

et al. 2009

Journal of the American Society of Nephrology

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Besides its classical effects on salt homeostasis in renal epithelial cells, aldosterone promotes inflammation and fibrosis and modulates cell proliferation. The proinflammatory transcription factor NF-B has been implicated in cell proliferation, apoptosis, and regulation of transepithelial sodium transport. The effect of aldosterone on the NF-B pathway in principal cells of the cortical collecting duct, a major physiologic target of aldosterone, is unknown. Here, in both cultured cells and freshly isolated rat cortical collecting duct, aldosterone activated the canonical NF-B signaling pathway, leading to increased expression of several NF-B-targeted genes (IB␣, plasminogen activator inhibitor 1, monocyte chemoattractant protein 1, IL-1␤, and IL-6). Small interfering RNA-mediated knockdown of the serum and glucocorticoid-inducible kinase SGK1, a gene induced early in the response to aldosterone, but not pharmacologic inhibition of extracellular signal-regulated kinase and p38 kinase, attenuated aldosterone-induced NF-B activation. Pharmacologic antagonism or knockdown of the mineralocorticoid receptor prevented aldosterone-induced NF-B activity. In addition, activation of the glucocorticoid receptor inhibited the transactivation of NF-B by aldosterone. In agreement with these in vitro findings, spironolactone prevented NF-B-induced transcriptional activation observed in cortical collecting ducts of salt-restricted rats. In summary, aldosterone activates the canonical NF-B pathway in principal cells of the cortical collecting duct by activating the mineralocorticoid receptor and by inducing SGK1.

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Section: Discussionsupporting

confidence: 77%

Aldosterone Activates NF-κB in the Collecting Duct

Leroy

Seigneux²,

Agassiz³

et al. 2009

Journal of the American Society of Nephrology

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“…In the present study, the serum creatinine, blood urea nitrogen and proteinuria were noted to be significantly increased in STZ-induced diabetic rats as compared to normal rats. The increased ratio of kidney weight/body weight may contribute to renal hypertrophy which leads to diabetic nephropathy progression (Fujisawa et al, 2004). These words are supported by our study that there is significant increase in the ratio of kidney weight/body weight in diabetic rats.…”

Section: Discussionsupporting

confidence: 71%

Effect of lutein in development of experimental diabetic nephropathy in rats

Katyal¹

2013

Afr. J. Pharm. Pharmacol.

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The present study has been designed to investigate the effect of lutein in streptzotocin induced diabetic nephropathy in Wistar rats. Diabetic nephropathy (DN) was induced by administering single dose of streptozotocin in Wistar rats. DN was clinically assessed by the estimation of various biochemical parameters and histopathological studies of renal tissue. Diabetic nephropathy was assessed biochemically by blood urea nitrogen, serum creatinine, total urinary protein. Oxidative stress assessed by measuring the thiobarbituric acid reactive substances (TBARS) level and renal reduced glutathione levels. Treatment with high dose of lutein (1.5 mg/kg, p.o.) shows significant improvement in (blood urea nitrogen (BUN), serum creatinine, total urine protein, ratio of kidney wt/body wt, TBARS, reduced glutathione) renal parameters studied for DN. It may therefore be concluded that renoprotective effect of lutein is due to its antioxidant property. Lutein may prevent overproduction of reactive oxygen species (ROS) and increase the removal of preformed ROS. This may prove to be effective in preventing the development and progression of diabetic nephropathy.

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“…112 The beneficial effects of aldosterone blockade on diabetic nephropathy seem to be independent of the blood pressure reduction 112 and RAAS blockade on diabetic nephropathy. 113 The mechanism by which an aldosterone blocker improves diabetic nephropathy is not totally clear; however, antiinflammatory 114,115 and/or anti-oxidant 116 mechanisms have been suggested as possibilities. To this end, it has been shown that the induction of diabetes in rats leads to a reduction in glucose-6-phosphate dehydrogenase (G6PD) and oxidative stress.…”

Section: Role Of Renin-ang Aldosterone System With Emphasis On Aldostmentioning

confidence: 99%

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

2011

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Diabetes and hypertension frequently coexist and constitute the most notorious combination for the pathogenesis of diabetic nephropathy and retinopathy. Large clinical trials have clearly demonstrated that tight control of glycemia and/or blood pressure significantly reduces the incidence and progression of diabetic retinopathy (DR) and nephropathy. However, the mechanism by which hypertension interacts with diabetes to induce and/or exacerbate nephropathy and retinopathy is very unclear. Substantial evidence implicates the involvement of chronic inflammation and oxidative stress in the pathogenesis of DR and nephropathy. In addition, hypertension causes oxidative stress and inflammation in the kidney and retina. In the present review, we summarized data obtained from our research along with those from other groups to better understand the role of hypertension in the pathogenesis of diabetic nephropathy and retinopathy. It is suggested that oxidative stress and inflammation may be common denominators of kidney and retinal damage in the concomitant presence of diabetes and hypertension.

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Spironolactone prevents early renal injury in streptozotocin-induced diabetic rats

Cited by 166 publications

References 56 publications

Aldosterone Activates NF-κB in the Collecting Duct

Aldosterone Activates NF-κB in the Collecting Duct

Effect of lutein in development of experimental diabetic nephropathy in rats

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

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