Renal Antioxidant Enzymes and Fibrosis-Related Markers in the Rat Adriamycin Model

Branden, Christiane Van Den; Ceyssens, Bart; Craemer, Dirk De; Pauwels, Marina; Houte, Katherina Vanden; Bleser, Pieter De; Hellemans, Karine; Geerts, Albert; Verbeelen, Dierik

doi:10.1159/000045736

Cited by 20 publications

(18 citation statements)

References 33 publications

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“…Excessive generation of reactive oxygen intermediates (ROI) contributes to the process of progressive renal injury in a variety of clinical and experimental renal diseases [2]. Previous work in relation to atherogenesis has focused on the importance of lipoprotein oxidation within the arterial wall [3].…”

Section: Introductionmentioning

confidence: 99%

Effects of Vitamins E, A and D on MDA, GSH, NO Levels and SOD Activities in 5/6 Nephrectomized Rats

Kır

Dillioğlugil²,

Tugay³

et al. 2005

Am J Nephrol

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Background: Excessive generation of reactive oxygen species (ROS) contributes to the process of progressive renal injury in a variety of clinical and experimental renal diseases. The present study was designed to test the hypothesis that treatment with vitamins decreases renal injury in chronic renal failure (CRF). Methods: Forty male Sprague-Dawley rats were divided into 5 groups: group 1, control; group 2, 5/6 nephrectomy (CRF); other groups 5/6 nephrectomy and injected vitamins (E, A, D). After 8 weeks, urea, creatinine and renal tissue malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels and superoxide dismutase (SOD) activities were determined. Results: Renal tissue MDA levels were significantly lower in the control and Vit E groups compared to that of the CRF, Vit A and Vit D groups. GSH levels were significantly higher in the control group compared to that of other groups. However, GSH levels were significantly lower in the control group than those in the other groups. SOD activities of the control group were significantly higher than those in the other groups. SOD activities were significantly decreased in the Vit E group compared to the Vit A and Vit D groups. Tissue NO levels of control group were significantly increased compared to the other groups. Conclusion: According to this study, Vit E may at least in part prevent tissue injury by acting as a free radical scavenger.

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Section: Introductionmentioning

confidence: 99%

Effects of Vitamins E, A and D on MDA, GSH, NO Levels and SOD Activities in 5/6 Nephrectomized Rats

Kır

Dillioğlugil²,

Tugay³

et al. 2005

Am J Nephrol

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“…For example, under diabetic conditions in which oxidative stress plays an important role in the development of complications involving oxidant injury (Maiese et al, 2007;Kaneto et al, 2007), SOD activity has been shown to be reduced (Godin et al, 1988) or unaffected , CAT activity increased (Matkovics et al, 1982;Yadav et al,1997) or unaffected (Kakkar et al,1995) and GSH-Px activity increased (Godin et al, 1988;Kakkar et al, 1995;Duncan et al, 1996) or decreased (Tagami et al, 1992;Van den Branden et al, 2000). Antioxidant enzyme activities are also altered in chronic renal failure (CRF) in which oxidative stress also plays an important part (Modlinger et al, 2004), however, as with diabetic conditions, the true effects are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Antioxidant Enzyme Expression and Activity by Paraquat in Renal Epithelial NRK-52E Cells

Samai¹,

Boccuti²,

Samai³

et al. 2011

Sierra Leone j. biomed. res.

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Renal toxicity produced by paraquat involves the generation of reactive oxygen species (ROS) which can overwhelm antioxidant defences, leading to oxidant injury. However, there are conflicting reports regarding the activity and/or expression of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) during oxidative stress injury. This study investigated the activity and expression of these enzymes in a renal epithelial cell line following exposure to paraquat. Confluent NRK-52E cells were incubated with increasing concentrations of paraquat (1-100mM) for up to 24 hours. Renal cell death was determined by measurement of lactate dehydrogenase release. Oxidant damage was determined via measurement of malondialdehyde formation and DNA strand breaks. The effects of paraquat on DNA and de novo protein synthesis were determined using radio-labelled thymidine and leucine respectively. ROS generation (superoxide anion and hydroxyl radical formation) was measured using nitrobluetetrazolium and deoxyribose assays. Antioxidant enzyme activities and expression were measured using established biochemical assays and Western blot analysis. Exposure of confluent NRK-52E cells to paraquat resulted in significant cell death involving increased lipid peroxidation, DNA damage and inhibition of DNA and de novo protein synthesis. Renal cell injury and death were secondary to increased ROS generation. Incubation with paraquat reduced SOD and CAT activities; in contrast, GSH-Px activity increased significantly. Although SOD expression was significantly reduced, catalase expression was unaffected. These results indicate that paraquat mediates renal toxicity via oxidative stress involving both an increase in ROS generation and reductions in SOD and CAT activities with a concomitant reduction in SOD expression.

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“…It has been suggested that excessive generation of reactive oxygen intermediates [3,4], association of nitric oxide production, and apoptosis [5], are involved in the pathogenesis of adriamycin nephrotoxicity (AN). It has been demonstrated that animals with adriamycin nephropathy had increased nitrite levels and evidence of increased nitric oxide (NO) production in the renal vasculature, interstitial cell increment, and apoptosis and that these effects were suppressed by administration of nitric oxide synthase (NOS) inhibitors [5].…”

Section: Introductionmentioning

confidence: 99%

Beneficial effect of triple treatment plus immunoglobulin in experimental nephrotic syndrome

et al. 2009

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Combinations of antiproteinurics, including angiotensin I-converting enzyme inhibitors + angiotensin II receptor antagonist + statins, are promising choices in the treatment of steroid-resistant nephrotic syndrome. We aimed to investigate the effects of high doses of immunoglobulin in addition to these combinations in rats with adriamycin-induced nephrosis. The study included 40 rats allocated into five groups: control, nephrotic syndrome without treatment, dual therapy (DT) with enalapril + losartan, triple therapy (TT) with enalapril + losartan + simvastatin, and quadruple therapy (QT) with enalapril + losartan + simvastatin + a high dose of immunoglobulin. The proteinuria levels were not statistically different between DT, TT and QT groups at weeks 5, 8, 12 and 16. At week 16, serum creatinine levels in the QT group were significantly lower than those in the control, DT and TT groups. The glomerulosclerosis index in the DT group was significantly lower than in the TT and QT groups. The scores for interstitial fibrosis and TGF-beta staining were similar among treatment groups. In conclusion, we showed that quadruple therapy including immunoglobulin had a beneficial effect on renal function in the late phase, but it had no additional effects in reducing proteinuria or in glomerulosclerosis score in experimental nephrotic syndrome. Further studies with angiotensin I-converting enzyme inhibitors (ACEIs), angiotensin II receptor antagonists (AIIRAs) and immunoglobulin combinations would offer some benefits in the treatment of nephrotic syndrome.

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Renal Antioxidant Enzymes and Fibrosis-Related Markers in the Rat Adriamycin Model

Cited by 20 publications

References 33 publications

Effects of Vitamins E, A and D on MDA, GSH, NO Levels and SOD Activities in 5/6 Nephrectomized Rats

Effects of Vitamins E, A and D on MDA, GSH, NO Levels and SOD Activities in 5/6 Nephrectomized Rats

Modulation of Antioxidant Enzyme Expression and Activity by Paraquat in Renal Epithelial NRK-52E Cells

Beneficial effect of triple treatment plus immunoglobulin in experimental nephrotic syndrome

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