Plasma aminothiol oxidation in chronic hemodialysis patients

Himmelfarb, Jonathan; McMenamin, Elizabeth; McMonagle, Ellen

doi:10.1046/j.1523-1755.2002.00151.x

Cited by 89 publications

(57 citation statements)

References 59 publications

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“…[57] Several experimental studies have shown that antioxidant capacity of tissues is decreased in animals with CRF, [58,59] while marked reductions in plasma glutathione concentration and glutathione peroxidase activity, as well as marked increases in the ratios of oxidized to reduced GSH were observed in CRF patients. [60,61] Current findings show that the reduction in GSH content of the studied tissues of male and ovariectomized rats may be due to its consumption during CRF-induced oxidative stress. On the other hand, administration of E 2 , through its antioxidant properties and by inhibiting lipid peroxidation, maintained the glutathione levels and thereby protected the tissues against oxidative stress.…”

Section: Discussionmentioning

confidence: 91%

Estrogen Protects against Oxidative Multiorgan Damage in Rats with Chronic Renal Failure

et al. 2009

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The impact of sex dimorphism on chronic renal failure (CRF)-induced oxidative multiorgan damage and the effects of estradiol (E 2 ) loss and E 2 supplementation on the progress of CRF were studied. Sprague-Dawley rats underwent 5/6 nephrectomy (CRF), and a group of female rats had bilateral ovariectomy (OVX), while the sham-operated rats had no nephrectomy or OVX. Rats received either estradiol propionate (50 μg/kg/day) or vehicle for six weeks. Serum BUN levels were elevated in both male and female CRF groups treated with vehicle, while creatinine level was not significantly changed in the female CRF group. CRF-induced elevation in serum TNF-a of male rats was abolished when the animals were treated with E 2 , while OVX exaggerated TNF-a response. In OVX and male rats with CRF, E 2 treatment reversed the malondialdehyde elevations in all the studied tissues (kidney, heart, lung, ileum, brain, liver, and gastrocnemius muscle), while depletion of glutathione in these tissues was prevented by E 2 treatment. Similarly, increased levels of myeloperoxidase activity, lucigenin chemiluminescence, and collagen in most of the tissues were reversed by E 2 treatment. The findings show that the extent of tissue injuries was relatively less in females, while ovariectomy exacerbated all the indices of oxidative injury. Moreover, the administration of E 2 , with its potent anti-oxidant and anti-inflammatory effects, markedly improved CRF-induced systemic inflammatory outcomes in both male and female rats by depressing tissue neutrophil infiltration and modulating the release of inflammatory cytokines.

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Section: Discussionmentioning

confidence: 91%

Estrogen Protects against Oxidative Multiorgan Damage in Rats with Chronic Renal Failure

et al. 2009

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“…Fourth, previous data from our group and others have suggested that oxidation of thiol groups, particularly in plasma proteins, is especially prominent in persons with kidney disease. 29,30 Finally, we hypothesized that combining predominantly lipophilic antioxidants (tocopherols) with more water-soluble antioxidants (ALA) would provide synergistic antioxidant effect.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have demonstrated that low-molecular-weight thiols and plasma protein thiols are markedly oxidized in patients undergoing MHD. 29,30 In a prospective randomized clinical trial, administration of the thiol-containing antioxidant N-acetylcysteine markedly decreased the cardiovascular event rate in a cohort of MHD patients, suggesting potential utility for this approach. 31 a-Lipoic acid (ALA) is a thiol-containing antioxidant that can replete reduced thiol groups, restore intracellular glutathione levels, and participate in the redox recycling of ascorbate and tocopherols.…”

mentioning

confidence: 99%

Provision of Antioxidant Therapy in Hemodialysis (PATH)

Himmelfarb

İkizler²,

Ellis³

et al. 2014

Journal of the American Society of Nephrology

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Increased markers of oxidative stress and acute-phase inflammation are prevalent in patients undergoing maintenance hemodialysis therapy (MHD), and are associated with increased mortality and hospitalization rates and decreased erythropoietin responsiveness. No adequately powered studies have examined the efficacy of antioxidant therapies on markers of inflammation and oxidative stress. We tested the hypothesis that oral antioxidant therapy over 6 months would decrease selected biomarkers of acute-phase inflammation and oxidative stress and improve erythropoietic response in prevalent MHD patients. In total, 353 patients were enrolled in a prospective, placebo-controlled, double-blind clinical trial and randomly assigned to receive a combination of mixed tocopherols (666 IU/d) plus a-lipoic acid (ALA; 600 mg/d) or matching placebos for 6 months (NCT00237718); 238 patients completed the study. High-sensitivity C-reactive protein (hsCRP) and IL-6 concentration were measured as biomarkers of systemic inflammation, and F2 isoprostanes and isofurans were measured as biomarkers of oxidative stress. The groups did not significantly differ at baseline. At 3 and 6 months, the treatment had no significant effect on plasma hsCRP, IL-6, F2 isoprostane, or isofuran concentrations and did not improve the erythropoietic response. No major adverse events were related to the study drug, and both groups had similar mortality and hospitalization rates during the study. In conclusion, the administration of mixed tocopherols and ALA was generally safe and well tolerated, but did not influence biomarkers of inflammation and oxidative stress or the erythropoietic response.

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“…5 It is interesting to note that patients with chronic renal failure also develop evidence for systemic inflammation and oxidant stress. 26,27 Oxidant stress is believed to be a major pathogenic factor in the cardiovascular disease seen in renal failure, 31 as well as the general population. 32 The concept that hormonal adaptations to decreases in renal function might participate in the pathogenesis of the uremic syndrome was elaborated in the 1960s.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, we found that animals subjected to partial nephrectomy developed systemic oxidant stress along with alterations of diastolic function quite consistent with that seen in patients afflicted with chronic renal failure. 31,34 This was not very surprising, because the rat partial nephrectomy model has been extensively studied as a model for chronic renal failure. 4 Next, we saw that infusion of 10 g/kg per day of MBG, which produces levels comparable to those in partial nephrectomy rats, produced almost identical increases in the plasma level of MBG to that seen with partial nephrectomy.…”

Section: Discussionmentioning

confidence: 99%

Central Role for the Cardiotonic Steroid Marinobufagenin in the Pathogenesis of Experimental Uremic Cardiomyopathy

et al. 2006

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Abstract-Patients with chronic renal failure develop a "uremic" cardiomyopathy characterized by diastolic dysfunction, cardiac hypertrophy, and systemic oxidant stress. Patients with chronic renal failure are also known to have increases in the circulating concentrations of the cardiotonic steroid marinobufagenin (MBG). On this background, we hypothesized that elevations in circulating MBG may be involved in the cardiomyopathy. First, we observed that administration of MBG (10 g/kg per day) for 4 weeks caused comparable increases in plasma MBG as partial nephrectomy at 4 weeks. MBG infusion caused increases in conscious blood pressure, cardiac weight, and the time constant for left ventricular relaxation similar to partial nephrectomy. Decreases in the expression of the cardiac sarcoplasmic reticulum ATPase, cardiac fibrosis, and systemic oxidant stress were observed with both MBG infusion and partial nephrectomy. Next, rats were actively immunized against a MBG-BSA conjugate or BSA control, and partial nephrectomy was subsequently performed. Immunization against MBG attenuated the cardiac hypertrophy, impairment of diastolic function, cardiac fibrosis, and systemic oxidant stress seen with partial nephrectomy without a significant effect on conscious blood pressure. These data suggest that the increased concentrations of MBG are important in the cardiac disease and oxidant stress state seen with renal failure.

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Plasma aminothiol oxidation in chronic hemodialysis patients

Abstract: Plasma aminothiols are excessively oxidized in uremia, while the hemodialysis procedure is restorative of redox status. Oxidized aminothiols are candidate uremic toxins.

Cited by 89 publications

References 59 publications

Estrogen Protects against Oxidative Multiorgan Damage in Rats with Chronic Renal Failure

Estrogen Protects against Oxidative Multiorgan Damage in Rats with Chronic Renal Failure

Provision of Antioxidant Therapy in Hemodialysis (PATH)

Central Role for the Cardiotonic Steroid Marinobufagenin in the Pathogenesis of Experimental Uremic Cardiomyopathy

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