Renal effects of N-acetylcysteine in patients at risk for contrast nephropathy: decrease in oxidant stress-mediated renal tubular injury.

Luciano F Drager; Lúcia Andrade; João Felipe Barros de Toledo; Francisco R M Laurindo; Luiz Antônio Machado César; Antonio Carlos Seguro

doi:10.1093/ndt/gfh261

PubMed · 15128882

Renal effects of N-acetylcysteine in patients at risk for contrast nephropathy: decrease in oxidant stress-mediated renal tubular injury.

Luciano F Drager·Lúcia Andrade·João Felipe Barros de Toledo·Francisco R M Laurindo·Luiz Antônio Machado César·Antonio Carlos Seguro

View original source ↗Export metadata ↓

Abstract

BACKGROUND: N-Acetylcysteine has been shown to protect against contrast nephropathy, although the mechanisms underlying such an effect are unclear. Surprisingly, studies have shown that post-radiocontrast renal function actually improves in chronic renal failure patients receiving N-acetylcysteine. However, there have been no studies investigating the cause of this improvement. METHODS: In a double-blind, placebo-controlled study, 24 patients (aged 65+/-2 years) suffering from stable mild-to-moderate renal insufficiency and undergoing elective coronary angiography were randomized to receive either placebo or N-acetylcysteine. All received similar hydration. Renal function parameters were assessed 48 h before and 48 h after radiocontrast administration. Urinary 15-isoprostane F2(t), a specific marker of oxidative stress, was measured immediately before and after the procedure. Expression of urinary alpha-glutathione S-transferase protein, a specific proximal tubular injury marker, was assessed after the procedure. RESULTS: Comparing creatinine clearance values before and after angiography, a significant increase was seen in N-acetylcysteine patients (44.7+/-4.2 vs 57.2+/-6.3 ml/min/1.73 m(2); P = 0.02), whereas placebo patients presented no change (46.6+/-5.0 vs 46.9+/-4.3 ml/min/1.73 m(2); P = 0.90). After radiocontrast, urinary 15-isoprostane F2(t) levels in placebo patients increased significantly over baseline values (2.9+/-0.7 vs 10.3+/-2.1 ng/mg creatinine; P = 0.007), whereas urinary 15-isoprostane F2(t) levels in N-acetylcysteine patients remained basically unchanged (3.5+/-0.5 vs 4.1+/-0.9 ng/mg creatinine; P = 0.63). Furthermore, N-acetylcysteine treatment led to lower levels of alpha-glutathione S-transferase than did placebo treatment (0.8+/-0.2 vs 2.4+/-0.7 micro g/g; P = 0.046). CONCLUSIONS: In chronic renal failure patients, the improvement in renal function induced by post-radiocontrast administration of N-acetylcysteine is strongly associated with suppression of oxidant stress-mediated proximal tubular injury.

Explore related subjects

Acetylcysteine Adolescent Adult Aged Aged, 80 and over Contrast Media Double-Blind Method Female Humans Kidney Diseases Kidney Failure, Chronic Kidney Tubules Male Middle Aged Oxidative Stress Risk Factors Clinical Trial Journal Article Randomized Controlled Trial

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Luciano F Drager, Lúcia Andrade, João Felipe Barros de Toledo, Francisco R M Laurindo, Luiz Antônio Machado César, Antonio Carlos Seguro. 2004-05-05. Renal effects of N-acetylcysteine in patients at risk for contrast nephropathy: decrease in oxidant stress-mediated renal tubular injury.. https://doi.org/10.1093/ndt%2Fgfh261

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Differential involvement of reactive oxygen species in apoptosis induced by two classes of selenium compounds in human prostate cancer cells.

Selenium is a promising chemopreventive agent for prostate cancer, possibly via an induction of apoptosis. Earlier studies have shown that selenite induces DNA single strand breaks (SSBs), reactive oxygen species (ROS), p53 Ser-15 phosphorylation and caspase-dependent and -independent apoptosis, whereas a methylselenol precursor methylseleninic acid (MSeA) induces caspase-mediated apoptosis regardless of p53 status. Here we address three main questions: What types of ROS are induced by selenite vs. MSeA in LNCaP (p53 wild type, androgen-responsive) and DU145 (mutant p53, androgen-independent) prostate cancer cells? Does ROS generation depend on androgen signaling? What are the relationships among ROS, DNA SSBs, p53 and caspases? We show that selenite (5 microM) induced superoxide and hydrogen peroxide in LNCaP cells much more than in DU145 cells and the ROS generation was not affected by physiological androgen stimulation. MSeA (10 microM) induced apoptosis without either type of ROS in both cell lines. In LNCaP cells, we established superoxide as a primary mediator for selenite-induced DNA SSBs, p53 activation and caspase-mediated apoptosis. Furthermore a p53-dominant negative mutant attenuated selenite-induced ROS, leading to a proportionate protection against apoptosis. The results support the p53-mitochondria axis in a feedback loop for sustaining superoxide production to lead to efficient caspase-mediated apoptosis by selenite. In contrast, caspase-mediated apoptosis induced by MSeA does not involve ROS induction. Since p53 is frequently mutated or deleted in prostate cancer and many other cancers, our results suggest that genotoxic vs. nongenotoxic classes of selenium may exert differential apoptosis efficacy depending on the p53 status of the cancer cells.

Acetylcysteine↗

PubMed2007

Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production.

Reactive oxygen species are involved in the aging process and diseases. Despite the important role of Cu/Zn SOD (superoxide dismutase) encoded by SOD1, SOD1-/- mice appear to grow normally under conventional breeding conditions. In the present paper we report on a novel finding showing a distinct connection between oxidative stress in erythrocytes and the production of autoantibodies against erythrocytes in SOD1-/- mice. Evidence is presented to show that SOD1 is primarily required for maintaining erythrocyte lifespan by suppressing oxidative stress. A SOD1 deficiency led to an increased erythrocyte vulnerability by the oxidative modification of proteins and lipids, resulting in anaemia and compensatory activation of erythropoiesis. The continuous destruction of oxidized erythrocytes appears to induce the formation of autoantibodies against certain erythrocyte components, e.g. carbonic anhydrase II, and the immune complex is deposited in the glomeruli. The administration of an antioxidant, N-acetylcysteine, suppressed erythrocyte oxidation, ameliorated the anaemia, and inhibited the production of autoantibodies. These data imply that a high level of oxidative stress in erythrocytes increases the production of autoantibodies, possibly leading to an autoimmune response, and that the intake of antioxidants would prevent certain autoimmune responses by maintaining an appropriate redox balance in erythrocytes.

Acetylcysteine↗

PubMed2007

Premedication with pronase or N-acetylcysteine improves visibility during gastroendoscopy: an endoscopist-blinded, prospective, randomized study.

AIM: To assess the efficacy of premedicaton with pronase or N-acetylcysteine (NAC) at 20 min before upper gastrointestinal (UGI) endoscopy and to determine whether pronase or NAC pretreatment influences the reliability of the rapid urease test. METHODS: A total of 146 patients were prospectively and randomly assigned into the study groups according to different premedications before endoscopy. One endoscopist assessed mucosal visibility (MV) with scores ranged from 1 to 4 at four sites in the stomach. The sum of the MV scores from these four locations was defined as the total mucosal visibility (TMV) score. Identification of H pylori was performed using CLO test, histology, and serology. RESULTS: The Group with pronase premedication had a significantly lower TMV score than did the groups with gascon and gascon water (P < 0.001 and P < 0.01, respectively). The group with NAC had a significantly lower TMV score than the group with gascon (P < 0.01) and a trend of a lower MV score than the group with gascon water (P = 0.06). The TMV score did not significantly differ between the group with pronase and the group with NAC (P = 0.39 and P = 0.14, respectively). The sensitivity and specificity of the CLO test were 92.5% and 93.9%, respectively, in groups premedicated with pronase and NAC together. CONCLUSION: Premedication with pronase or NAC at 20 min before UGI endoscopy improves the mucosal visibility of the stomach. Neither pronase nor NAC produces any obvious interference with the CLO test for the identification of H pylori infection.

Acetylcysteine↗