Vitamin E suppresses oxidative stress and glomerulosclerosis in rat remnant kidney

Hahn, Seung Hoon; Krieg, Richard J.; Hisano, Satoshi; Chan, Winnie; Kuemmerle, Nancy B.; Saborío, Pablo; Chan, James C.M.

doi:10.1007/s004670050591

Cited by 39 publications

(25 citation statements)

References 21 publications

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“…28,29 The traditional antioxidant, Vit E, was found to cause significant reduction of glomerulosclerosis but no change in creatinine clearance or proteinuria with supplementation for 15 weeks in 5/6 nephrectomized rats. 12 Similar findings were reported by Van den Branden et al and Hahn et al 30,31 Our results showed not only a marked structural improvement but also an impressive preservation of renal function and reduction of proteinuria with ALA administration in the progression of this model. Furthermore, these benefits can be maintained after the cessation of treatment.…”

Section: Discussionsupporting

confidence: 91%

Oxidative Stress in 5/6 Nephrectomized Rat Model: Effect of Alpha-Lipoic Acid

et al. 2012

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Alpha-lipoic acid (ALA) is a powerful antioxidant, and its effect in ameliorating complications of diabetes mellitus has been widely documented. The aim of this study was to investigate the role of ALA in the disease progression of remnant kidneys (RK). Systolic blood pressure (SBp), hemoglobin, renal function, kidney malondialdehyde (MDA), glutathione (GSH), vitamin E (Vit E) concentrations, p65 nuclear factor (NF)-κB activity, and macrophage infiltration were analyzed in sham and RK rats supplemented with ALA (100 mg/kg body weight, i.p., every other day) or vehicle for 12 weeks. RK rats exhibited increases in SBp, kidney MDA concentration, p65 NF-κB activity, and macrophage infiltration, which were prominent in weeks 4 and 8 and decreased at week 12. RK rats also showed anemia, microalbuminuria, and decreased renal function and kidney GSH and Vit E concentrations. These changes were all attenuated by 8 weeks of ALA treatment compared to RK vehicle group. But the continued ALA treatment after week 8 reversed the beneficial effect on SBp, kidney MDA concentration, p65 NF-κB activity, macrophage infiltration, anemia, microalbuminuria, and renal function, while the beneficial effect was maintained if the treatment was discontinued after week 8. Furthermore, ALA increased albuminuria and kidney MDA concentration in sham animals. In conclusion, ALA administration attenuates oxidative stress, inflammation, and hypertension and delayed the deterioration of kidney function in RK rats with enhanced oxidative stress, while in healthy animals or RK rats with a well-balanced redox state, ALA may act as a pro-oxidant, contributing to renal dysfunction.

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Section: Discussionsupporting

confidence: 91%

Oxidative Stress in 5/6 Nephrectomized Rat Model: Effect of Alpha-Lipoic Acid

et al. 2012

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“…In a recent study, Tain et al (40) found significant reduction of glomerulosclerosis but no change in creatinine clearance or proteinuria with vitamin E supplementation for 15 wk in 5/6 nephrectomized rats. Similar findings were reported by Van den Branden et al (43) and Hahn et al (7). It should be noted that the use of high doses of antioxidant vitamins in humans has been hampered by the general lack of significant demonstrable benefit and the emerging evidence of adverse outcome found in clinical trials (18).…”

supporting

confidence: 78%

“…Early studies (7,43) showed that vitamin E supplementation reduces glomerulosclerosis in the remnant kidney model. These observations were confirmed in a recent study by Tain et al (40) who found amelioration of glomerulosclerosis without improvement in renal function or proteinuria in 5/6 nephrectomized rats.…”

Section: F340mentioning

confidence: 99%

Melatonin ameliorates oxidative stress, inflammation, proteinuria, and progression of renal damage in rats with renal mass reduction

Quiroz

Ferrebuz²,

Romero³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…Increased angiotensin II levels are associated with podocyte loss in 5/6 nephrectomy animals (16). Antioxidants prevent increases in transforming growth factor (TGF)-␤1, restore neuronal nitric oxide synthase expression in the kidney, and delay progression of glomerular sclerosis in 5/6 nephrectomy rats (18,38).…”

Section: Discussionmentioning

confidence: 99%

N-acetylcysteine ameliorates acute kidney injury but not glomerular hemorrhage in an animal model of warfarin-related nephropathy

Ware

Qamri

Özcan

et al. 2013

American Journal of Physiology-Renal Physiology

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Ware K, Qamri Z, Ozcan A, Satoskar AA, Nadasdy G, Rovin BH, Hebert LA, Nadasdy T, Brodsky SV. N-acetylcysteine ameliorates acute kidney injury but not glomerular hemorrhage in an animal model of warfarin-related nephropathy. Am J Physiol Renal Physiol 304: F1421-F1427, 2013. First published April 10, 2013 doi:10.1152/ajprenal.00689.2012.-Warfarin-related nephropathy (WRN) occurs under conditions of overanticoagulation with warfarin. WRN is characterized by glomerular hemorrhage with occlusive tubular red blood cell (RBC) casts and acute kidney injury (AKI). Herein we test the hypothesis that oxidative stress plays a role in the AKI of WRN. 5/6 Nephrectomy rats were treated with either warfarin (0.04 mg·kg Ϫ1 ·day Ϫ1 ) alone or with four different doses of the antioxidant N-acetylcysteine (NAC). Also tested was the ability of our NAC regimen to mitigate AKI in a standard ischemia-reperfusion model in the rat. Warfarin resulted in a threefold or greater increase in prothrombin time in each experimental group. Serum creatinine (Scr) increased progressively in animals receiving only warfarin ϩ vehicle. However, in animals receiving warfarin ϩ NAC, the increase in Scr was lessened, starting at 40 mg·kg Ϫ1 ·day Ϫ1 NAC, and completely prevented at 80 mg·kg Ϫ1 ·day Ϫ1 NAC. NAC did not decrease hematuria or obstructive RBC casts, but mitigated acute tubular injury. Oxidative stress in the kidney was increased in animals with WRN and it was decreased by NAC. The NAC regimen used in the WRN model preserved kidney function in the ischemia-reperfusion model. Treatment with deferoxamine (iron chelator) did not affect WRN. No iron was detected in tubular epithelial cells. In conclusion, this work taken together with our previous works in WRN shows that glomerular hematuria is a necessary but not sufficient explanation for the AKI in WRN. The dominant mechanism of the AKI of WRN is tubular obstruction by RBC casts with increased oxidative stress in the kidney. oxidative stress; warfarin-related nephropathy; 5/6 nephrectomy WE SHOWED THAT WARFARIN coagulopathy induces acute kidney injury (AKI) that is associated with severe glomerular hematuria causing widespread tubular obstruction by red blood cell (RBC) casts (5-7). We documented this association in both humans (5-7) and animal models (31, 41). We named this condition warfarin-related nephropathy (WRN). WRN can have dire consequences, particularly in chronic kidney disease (CKD) patients, whose CKD progression can be accelerated (5, 6). In humans, WRN is not an uncommon complication of excessive anticoagulation with warfarin. Our retrospective studies show that when the international normalized ratio (INR) acutely exceeds 3.0, 16% of non-CKD patients (6) and 33-37% of CKD patients (5, 6) may develop AKI within ϳ1 wk of the INR Ͼ 3.0. Those at greatest risk of WRN have CKD or cardiovascular disease (5, 6).The most conspicuous feature of WRN is the presence of numerous renal tubules obstructed by RBC casts. On this basis, it has been assumed that the tubular obstruction was t...

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Vitamin E suppresses oxidative stress and glomerulosclerosis in rat remnant kidney

Cited by 39 publications

References 21 publications

Oxidative Stress in 5/6 Nephrectomized Rat Model: Effect of Alpha-Lipoic Acid

Oxidative Stress in 5/6 Nephrectomized Rat Model: Effect of Alpha-Lipoic Acid

Melatonin ameliorates oxidative stress, inflammation, proteinuria, and progression of renal damage in rats with renal mass reduction

N-acetylcysteine ameliorates acute kidney injury but not glomerular hemorrhage in an animal model of warfarin-related nephropathy

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