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

Lei, Yu; Liu, Hong; Zou, Jianzhou; Zhu, Jiaming; Xu, Xunhui; Ding, Xiaoqiang

doi:10.3109/0886022x.2012.691012

Cited by 16 publications

(18 citation statements)

References 35 publications

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“…High oxidative stress levels, as indicated by plasma MDA concentration, was found to be significantly higher in Nx animals [31–33]. This finding is in agreement with our observation in nephrectomized rats.…”

Section: Discussionsupporting

confidence: 90%

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L-carnosine alters some hemorheologic and lipid peroxidation parameters in nephrectomized rats

Taşkın

2014

Med Sci Monit

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Background:Chronic kidney disease (CKD) is a major health problem worldwide. Oxidative stress is one of the mediators of this disease. Systemic complications of oxidative stress are involved in the pathogenesis of hypertension, endothelial dysfunction, shortened erythrocyte lifespan, deformability, and nitric oxide (NO) dysfunction. L-carnosine is known as an antioxidant. In this study, our aim was to investigate the effect of carnosine on hemorheologic and cardiovascular parameters in CKD-induced rats. Material/Methods:We used 4-month-old male Sprague-Dawley rats divided into 4 groups of 6 rats each. Three days after subtotal nephrectomy and sham operations, the surviving rats were divided into the 4 groups; 1) Sham (S), 2) Sham+Carnosine (S-C), 3) Subtotal nephrectomy (Nx), and 4) Subtotal nephrectomy + Carnosine (N-C). Carnosine was injected intraperitoneally (i.p.) (50 mg/kg) for 15 days. The control group received the same volume of physiological saline. Results:In CKD rats, malondialdehyde (MDA) levels were increased, and NO and RBC deformability were decreased compared to Sham. Carnosine treatment decreased MDA levels, improved RBC (red blood cell) ability to deform, and increased NO levels. However, carnosine did not affect blood pressure levels in these rats. Conclusions:We found that carnosine has beneficial effects on CKD in terms of lipid peroxidation and RBC deformability. Carnosine may have a healing effect in microcirculation level, but may not have any effect on systemic blood pressure in CKD-induced rats.

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Section: Discussionsupporting

confidence: 90%

“…Several studies reported a beneficial effect of antioxidant treatment on MDA concentration or ROS in CKD. One of these studies showed that alpha-lipoic acid, an antioxidant, attenuated kidney MDA concentration in Nx rats [33]. Another study reported that sildenafil-treated Nx rats had decreased ROS levels [34].…”

Section: Discussionmentioning

confidence: 99%

L-carnosine alters some hemorheologic and lipid peroxidation parameters in nephrectomized rats

Taşkın

2014

Med Sci Monit

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“…Indeed, beneficial effects of LA in the 5/6 nephrectomy model in rats have been observed with intraperitoneal injections of LA. 13 However, it has been reported that the oral administration presents the highest LD50 in rats and mice, when compared with other routes of application.…”

Section: Discussionmentioning

confidence: 99%

“…Although some studies showed that oral administration of LA, particularly to hemodialysis (HD) patients for several weeks, led to an improvement in asymmetric dimethylarginine (ADMA) 7 and C-reactive protein 8 levels, or erythropoietin resistance index, 9 oxidative stress biomarkers levels were not altered in the LA-treated groups of CKD 10 or HD patients. 8,9,11,12 In experimental CKD, intraperitoneally-injected LA for 8 weeks has been shown to improve blood pressure, renal function, and oxidative markers after 5/6 nephrectomy in rats, 13 while oral LA for 8 weeks decreased blood pressure, as well as vascular injury 14 when compared with the non-treated nephrectomized rats. In acetaminophen-induced uremia, orally-fed LA for 15 days prevented an increase in plasma urea, creatinine, and malondialdehyde levels in rats.…”

Section: Introductionmentioning

confidence: 99%

“…16 For instance, LA may have toxic effects in healthy organisms, leading to renal tissue damage. 13,30 Yu et al 13 performed the 5/6 nephrectomy in 2-steps (ablation of 2/3 of the left kidney and removal of the right kidney one week later) and we did it in 1-step (infarction of 2/3 of the left kidney and removal of the right kidney in the same surgery). These two methods of inducing renal insufficiency produce pathological consequences in dissimilar extensions.…”

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confidence: 99%

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Lipoic acid does not improve renal function markers in 5/6 nephrectomy model: possible role of Nrf2 inactivation

Lin

Soares

et al. 2016

Renal Failure

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Chronic kidney disease (CKD) progression and complications are associated with increased oxidative stress, as well as with Nrf2 inactivation. Lipoic acid (LA) has been considered an inducer of Nrf2 antioxidant response. We tested whether oral administration of LA provides beneficial effects in experimental CKD in rats. Wistar rats underwent 5/6 nephrectomy (CKD group) or sham laparotomy. Seven days later, CKD group was divided into three subgroups that received: (i) LA continuously in the drinking water (100 mg/kg/day), (ii) LA by gavage every other day (100 mg/kg), or (iii) no LA treatment. LA treatment lasted until day 60. Plasma urea and creatinine, 24 hproteinuria, glomerulosclerosis, interstitial fibrosis/tubular atrophy, and Nrf2 activation were analyzed. All parameters measured were significantly altered in the untreated CKD group, compared with the sham group, as expected. Oral LA administration, either in the drinking water or by gavage, did not improve significantly any parameter, comparing the treated-groups with the untreated CKD group. These results indicate that oral LA administration for 53 days was ineffective to reactivate Nrf2 in the remnant kidney of uremic rats, likely preventing improvements in biochemical and histopathological markers of renal function. ARTICLE HISTORY

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Tangeretin ameliorates renal failure via regulating oxidative stress, NF-κB–TNF-α/iNOS signalling and improves memory and cognitive deficits in 5/6 nephrectomized rats

Zhao

Deng

2017

Inflammopharmacol

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Chronic kidney disease (CKD) is a significant global health concern with limited treatment options. Oxidative stress and inflammatory responses have been implicated in the pathology of CKD. Patients with CKD are frequently affected with neurological complications that affect both the central and peripheral nervous system. Identification of effective treatment strategies are of much clinical value in the therapy of CKD. Tangeretin, a plant-derived flavonoid has been described to retain extensive pharmacological properties. In the present study, we explored whether tangeretin exerted protective effects in 5/6 nephrectomized rats. CKD was induced in Sprague-Dawley rats by 5/6 nephrectomy (Nx). Separate groups of 5/6 Nx rats were treated with tangeretin (50, 100 or 200 mg/kg b.wt.) or enalapril for 30 days (starting 5 days after surgery for 35 days). Control animals were not subjected to Nx nor were treated with tangeretin or enalapril. Renal dysfunction, as evinced by raised serum urea, serum creatinine, proteinuria, and histological alterations were significantly reduced by tangeretin and enalapril treatment. 5/6 Nx animals exhibited raised levels of malondialdehyde (MDA) and reactive oxygen species. Elevated TNF-α, nitric oxide (NO) and cytokines-IL-6 and IL-1β with upregulated NF-κB/TNF-α/iNOS signalling pathways were effectively down-regulated by tangeretin. Cognitive disturbances and memory impairments observed in Nx rats were substantially improved by tangeretin. Collectively, the experimental data indicate that the anti-oxidant and anti-inflammatory effects of tangeretin effectively improved renal function and reduced the cognitive and memory impairments in CKD-induced animals.

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

Cited by 16 publications

References 35 publications

L-carnosine alters some hemorheologic and lipid peroxidation parameters in nephrectomized rats

L-carnosine alters some hemorheologic and lipid peroxidation parameters in nephrectomized rats

Lipoic acid does not improve renal function markers in 5/6 nephrectomy model: possible role of Nrf2 inactivation

Tangeretin ameliorates renal failure via regulating oxidative stress, NF-κB–TNF-α/iNOS signalling and improves memory and cognitive deficits in 5/6 nephrectomized rats

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