Effects of a Vitamin E-Modified Dialysis Membrane and Vitamin C Infusion on Oxidative Stress in Hemodialysis Patients

Hemodialysis deteriorates oxidative stress. Vitamin E is an antioxidant whose regeneration is provided for by vitamin C. The authors tested the effects of a vitamin E-modified membrane (E), nonmodified cellulose membrane (O), and vitamin C infusion (500 mg, C) into the arterial blood line during dialysis on parameters of oxidative stress. In a short-term study, 24 patients were subjected to a single dialysis session with E, O, E with C, and O with C protocols. In a long-term study (12 weeks), 20 patients were randomized into groups with C and without C on each dialysis, and both groups had dialysis using O, E, and again O membrane for 4 weeks each. In the short-term study, thiobarbituric acid reacting substances (TBARS) in plasma rose after dialysis (p < 0.02) with O, and no changes were observed in the other 3 protocols. In the long-term study, predialysis TBARS declined when using E both in the groups with C (p < 0.02) and without C (p < 0.05). A switch over to O resulted in TBARS returning to baseline levels. The E membrane prevented an increase in lipid peroxidation during single dialysis, and long-term use of the E membrane also resulted in a decrease in the predialysis lipid peroxidation level. The antioxidant capacity of the E membrane was not enhanced by vitamin C infusion. High doses of vitamin C administered during dialysis using a nonmodified cellulose membrane prevented an increase in lipid peroxidation, most probably due to the enhanced rate of endogenous vitamin E regeneration.     

Antioxidant Vitamin C attenuates experimental abdominal aortic aneurysm development in an elastase-induced rat model

Background

We investigated the hypothesis that an antioxidant, Vitamin C, could attenuate abdominal aortic aneurysm (AAA) development in a rat model.

Methods

An AAA model induced by intraluminal infusion was created in 36 male Sprague Dawley rats, which were randomly distributed into three groups: Sham (saline infused, placebo treated), Control (elastase infused, placebo treated), and Vitamin C (elastase infused, vitamin C treated). Vitamin C and placebo were intraperitoneally injected, initiating 1 wk before the infusion and continuing throughout the study. The aortic dilatation ratio was measured, and aortic tissues were further examined using biochemical and histologic techniques.

Results

Vitamin C attenuated the development of AAA, decreasing maximal aortic diameter by 25.8% (P < 0.05) and preserving elastin lamellae (P < 0.05). Vitamin C also decreased 8-hydroxyguanine (a marker of oxidative damage to DNA) and 8-isoprostane content (a marker of oxidative stress) in aortic tissues (P < 0.05, respectively). The proteins of matrix metalloproteinase (MMP)-2, MMP-9, and interleukin 6 were markedly downregulated (P < 0.05, respectively), accompanied with notably reduced messenger RNA expression of tumor necrosis factor-α, MMP-2/9, and interleukin 1β (P < 0.05, respectively). However, messenger RNA of tissue inhibitors of metalloproteinase-1 and tissue inhibitors of metalloproteinase-2 were both significantly upregulated in Vitamin C group. Vitamin C treatment had no significant effect on systolic blood pressure (P > 0.05).

Conclusions

Vitamin C attenuated AAA development in an elastase-induced rat model via crucial protective effect, which was mediated by an increased level of antioxidant in cooperation with preserving elastin lamellae, inhibiting matrix-degrading proteinases and suppressing inflammatory responses.     

血清胱抑素C对肝硬化病人肾功能损害的早期诊断价值研究

目的 探讨血清半胱氨酸蛋白酶抑制剂C(Cys C)检测对肝硬化病人肾功能损害早期诊断的意义.方法 测定76例肝硬化病人24 h肌酐清除率(Ccr)以及血清肌酐(SCr)和血清Cys C水平.以CCr＜80 ml/min/1.73 m2作为肾功能损害诊断标准,采用t检验、相关性分析和ROC曲线分析探讨Cys C的诊断价值.结果 在Child分级肝损害病人的肾功能评估能力比较中,Cys C能灵敏反映CCr变化,而Scr的反映能力明显低于Cys C.SCr与CCr有着显著的负相关性(CysC:r=-0.763,P＜0.001;SCr:r=-0.571,P＜0.01),而Cys C的相关系数较高.ROC曲线分析显示Cys C的曲线下面积(AUC)值明显高于SCr(0.830比0.612).结论 与SCr比较,Cys C能更准确地早期发现肝硬化病人的肾功能损害,常规监测肝硬化病人Cys C水平,对预防肝肾综合征的发生具有积极意义.     

Vitamin C and oxidative stress on cultured human keratinocytes

The aim of this research was to study the hypoxia-induced oxidative stress on cultured human keratinocytes. Control and cultured human keratinocytes were treated with vitamin C, and were then assessed by determining the concentration of malonyl dialdehyde (a final product of lipid peroxidation) existing in the cultured environment. Forty-eight flasks with culture of keratinocytes in confluent layer were divided into four groups: one control and one experimental group treated with vitamin C, and one control and one experimental group without vitamin C. All the cultures were sampled for malonyl dialdehyde assessment immediately after the end of a 30 min period of hypoxia. The statistical analysis of the results showed that vitamin C was not an effective protective agent against oxidative stress caused by hypoxia.     

Renal tubular cell damage and oxidative stress in renal stone patients and the effect of potassium citrate treatment

Our objective was to evaluate the oxidative stress and renal tubular cell damage in patients who have renal stones compared to normal subjects. The patients were re-evaluated after 1-months supplementation with potassium citrate. We recruited 30 patients (11 males and 19 females) diagnosed with kidney stones and scheduled for surgical stone removal the following month, and 30 healthy non-stone formers (14 males and 16 females). Two 24-h urine samples and one heparinized blood sample were collected from each subject. Plasma was separated from the erythrocytes and assayed for creatinine, potassium, sodium, calcium, magnesium, phosphate, malondialdehyde (MDA, a lipid peroxidation product) (P-MDA), protein thiol as an indicator of protein oxidation, and vitamin E. Erythrocytes were analysed for MDA (E-MDA), reduced glutathione (GSH) and cellular glutathione peroxidase (cGPx) activity. The urine was analyzed for pH, creatinine, potassium, sodium, calcium, magnesium, phosphate, oxalate, citrate, MDA (U-MDA), total protein (U-protein) and N-acetyl--glucosaminidase (NAG) activity. For the stone patients, urine and blood samples were re-evaluated after supplementation with potassium citrate (60 mEq/day) for 1 month. Renal stone patients had higher plasma creatinine and lower plasma potassium, urinary pH, potassium, magnesium, phosphate and citrate than the controls. The patients had higher P-MDA, E-MDA, U-MDA, U-protein and NAG activity, but lower GSH, cGPx activity, protein thiol and vitamin E, when compared with controls. After potassium citrate supplementation, P-MDA and E-MDA decreased while plasma vitamin E, urinary NAG activity and citrate increased. Renal stone disease is associated with high oxidative stress and damage to renal tubular cells. These abnormalities are coincident with an increase in blood lipid peroxidation products and a decrease in antioxidant status. Although supplementation with potassium citrate improved urinary citrate levels and oxidative stress, it neither reduced urinary lipid peroxidation products nor remedied the damage to renal tubular cells, probably due to the existence of kidney stones.     

维生素C联合依托咪酯对膝关节置换术后氧化应激及炎症因子水平的影响

目的 探讨维生素C注射液联合依托咪酯对膝关节置换术后病人氧化应激及炎症因子水平的影响。方法 纳入于我院行择期膝关节置换术的70例病人,按随机数字表法分为观察组和对照组。对照组给予丙泊酚辅助诱导麻醉及麻醉维持,观察组给予依托咪酯辅助麻醉诱导及麻醉维持,并在麻醉诱导前10 min、术中麻醉维持时、手术结束时及术后12 h分别予维生素C注射液0.5 g。于术前（T0）、术毕麻醉停止前（T1）、术后1 d（T2）、术后3 d（T3）、术后5 d（T4）这5个时间点分别抽取病人的外周静脉血,检测超氧化物歧化酶（SOD）、丙二醛（MDA）、肿瘤坏死因子-α（TNF-α）和白介素-6（IL-6）的水平。采用疼痛视觉模拟量表（VAS）对所有病人术后1、3、5 d的疼痛程度进行评分。结果 观察组中有1例退出研究,最终观察组纳入34例,对照组纳入35例。两组病人的年龄、性别、身体质量指数（BMI）、美国麻醉医师协会（ASA）分级、手术时间及止血带使用时间比较,差异均无统计学意义（P均＞0.05）。两组病人T0和T1时间点的SOD和MDA水平比较,差异无统计学意义（P＞0.05）;在T2、T3、T4时间点,观察组的SOD水平显著高于对照组,而MDA水平显著低于对照组（P＜0.05）;从T0到T4,SOD水平变化趋势为先降低,然后在T4点升高,MDA水平变化趋势为先升高,然后在T4点降低。两组病人T0时的TNF-α和IL-6水平比较,差异无统计学意义（P＞0.05）;在T1、T2、T3、T4时间点,观察组的TNF-α和IL-6水平显著低于对照组（P＜0.05）;从T0到T4,TNF-α和IL-6水平变化趋势为先升高,然后在T3点逐渐降低。观察组术后1、3 d的VAS评分显著低于对照组（P＜0.05）。结论 维生素C注射液联合依托咪酯可有效降低膝关节置换术病人的氧化应激水平和炎症反应,减小缺血再灌注损伤的影响,降低术后疼痛程度。     

Melatonin prevents acetaminophen-induced nephrotoxicity in rats

Nephrotoxicity is a major complication of acetaminophen (APAP), a widely used analgesic and antipyretic drug, and there is no specific treatment for APAP-induced renal damage. It has been reported that reactive oxygen metabolites or free radicals are important mediators of APAP toxicity. In this study, the protective role of melatonin (MLT) on APAP-induced nephrotoxicity was investigated in rats. For this purpose, nephrotoxicity was induced in male Wistar albino rats by intraperitoneal (i.p.) administration of a single dose of 1,000 mg/kg APAP. Some of these rats also received i.p. melatonin (10 mg/kg) 20 min after administration of APAP. The rats were sacrificed 24 h after administration of APAP. Urea and creatinine levels were measured in the blood, and levels of malondialdehyde (MDA) and glutathione (GSH), and glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) activity were determined in renal tissue. Serum urea and creatinine levels increased significantly as a result of APAP nephrotoxicity. A significant increase in MDA and decreases in GSH level and GSH-Px, CAT, and SOD activity indicated that APAP-induced renal damage was mediated through oxidative stress. Significant beneficial changes were noted in serum and tissue oxidative stress indicators in rats treated with MLT. These biochemical observations were supplemented by histopathological examination of kidney sections, which revealed that MLT also reduced the severity of APAP-induced histological alterations in the kidney. These results indicate that administration of APAP causes oxidative stress to renal tissue and that MLT protects against the oxidative damage associated with APAP.     

Vitamin C ameliorated cardiac autonomic neuropathy in type 2 diabetic rats

BACKGROUND Vitamin C(VC) is a common antioxidant with cell protection potentials.However, its possible protective effect on cardiac autonomic nerves from diabetic induced insults is yet to be explored.AIM To investigate the effects of VC on diabetic cardiac autonomic neuropathy.METHODS Thirty male Wistar rats were equally grouped into control, diabetic and diabetic +VC. Type 2 diabetes was induced with fructose diet and alloxan. VC(1 g/kg) was administered for 4 wk via oral canula. Blood pressure and heart rate were measured non-invasively using tail flick blood pressure monitor. Spectral analysis of heart rate variability(HRV) was used to assess cardiac autonomic neuropathy. Blood was collected from the ocular sinus for biochemical analysis.Urethane(1 g/kg-ip) was used for anaesthesia prior to HRV and cervical dislocation to harvest hearts. Intracardiac autonomic nerve was assessed using tyrosine hydroxylase immunohistochemistry on fixed heart sections.RESULTS Results were analysed using ANOVA at α0.05. Unlike VC and control groups,diabetic rats showed significantly(P 0.0001) reduced HRV, increased heart-rate and blood pressure, initial increase in cardiac tyrosine hydroxylase activities at week-2 and sparse activity at week-4 of diabetes. Furthermore, apolipoprotein B,Oxidative stress and inflammatory markers were significantly(P 0.01) reduced in VC treated rats.CONCLUSION VC possesses cardio-autonomic nerve protective potential and ameliorates the symptoms of cardiac autonomic neuropathy in type 2 diabetes. The possible mechanisms via which VC exert these effects may be via downregulation of oxidative stress, inflammation and apolipoprotein B.     

Markers of oxidative stress after renal transplantation

Abstract An increased degree of oxidative stress (OS) in chronic renal failure (CRF) and a possible role of free radicals in CRF have already been described. However, data on OS after renal transplantation are scarce. The aim of the present study was to estimate the degree of OS in renal transplant patients. The study included four groups: 1) 15 haemodialysis patients (HD group), 2) 11 renal transplant patients with stable function (SF group), 3) 12 renal transplant patients with chronic biopsy-proven rejection (CR group), and 4) 10 healthy controls (C group). Markers of OS (malondialdehyde and thiol group levels) and antioxidant activity (glutathione peroxidase and Cu, Zn-su-peroxide dismutase) were determined in plasma and in red blood cells of all examined individuals. After successful renal transplantation a significant improvement, but not normalization, of antioxidant enzyme activities accompanied by significantly reduced lipid peroxidation were found. In the CR group the degree of OS was increased, and our results suggest that OS may be a relevant pathophysiological factor for CR development.     

Vitamin C augments the renal response to L-arginine in smokers.

BACKGROUND: In the coronary and the forearm circulations, endothelium-dependent vasomotion is impaired in smokers, but can be augmented by -arginine or vitamin C. We examined whether smoking similarly affects the renal circulation. METHODS: In 20 smokers (age 26 +/- 4 years) and in 20 non-smokers (age 28 +/- 3 years) changes of renal plasma flow (RPF), glomerular filtration rate (GFR), blood pressure and heart rate in response to the subsequent intravenous infusions of N(G)-monomethyl--arginine (L-NMMA), -arginine and -arginine plus vitamin C were studied by use of a constant infusion input clearance technique. RESULTS: Systemic haemodynamic parameters did not differ between smokers and non-smokers during each experimental phase. At baseline, RPF and GFR were similar between the groups. The infusion of L-NMMA led to a similar decrease of RPF, while GFR did not change in either group. During the infusion of -arginine RPF increased similarly. Finally, the co-infusion of -arginine plus vitamin C led to a significantly greater increase of RPF (+277 +/- 395 vs +79 +/- 76 ml/min, P = 0.03) and GFR (+12.1 +/- 10.6 vs +3.4 +/- 11.2 ml/min, P = 0.02) in smokers as compared to non-smokers. CONCLUSIONS: L-NMMA-induced vasoconstriction of the renal vasculature was similar in smokers compared to non-smokers. -arginine alone induced a similar increase of RPF. The co-infusion of vitamin C and -arginine led to a greater increase of RPF and GFR in smokers. This might suggest that oxidative stress is increased in the renal vasculature of smokers.     

A review of the impact of oxidative stress and some antioxidant therapies on renal damage

An increase in the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to complications during chronic kidney disease (CKD). This increase essentially derives from the impairment of natural antioxidant systems of the organism. The resulting oxidative stress produces damage to kidney tissue, especially by affecting nephrons and more generally by disrupting the function and structure of the glomerulus and interstitial tubule. This leads to a rapid decline in the condition of the patient and finally renal failure. Possible causes of kidney tissue damage are explored, as are different therapies, especially those related to the administration of antioxidants.     

维生素C联合口服氨甲环酸治疗黄褐斑的疗效

目的 分析维生素C与氨甲环酸联合治疗黄褐斑的临床疗效。方法 选取我院2023年1月-6月收治的 76例黄褐斑患者作为研究对象,随机分为对照组和试验组,各38例。对照组开展口服维生素C与德菲林复 合酸抑菌凝露联合治疗,试验组在对照组基础上增加氨甲环酸治疗,比较两组色斑评分及色斑皮损面积、 临床效果及性激素水平。结果 试验组治疗后色斑颜色及色斑皮损面积评分低于对照组（P＜0.05）;试验 组治疗总有效率为97.37%,高于对照组的81.58%（P ＜0.05）;试验组治疗后黄体生成素、卵泡刺激素、雌 二醇水平低于对照组（P ＜0.05）。结论 维生素C联合口服氨甲环酸治疗黄褐斑的疗效较好,可改善患者 色斑情况和性激素水平。     

D二聚体、胱抑素C在糖尿病早期肾功能损伤诊断的临床研究

目的 研究D-二聚体（D-D）、胱抑素C（Cys C）对糖尿病患者肾功能监测的临床应用价值.方法 比较糖尿病患者中肾功能正常（62例）、肾功能不全代偿（57例）、肾功能不全失代偿（49例）患者D-D及Cys C检测情况,研究D-D及Cys C与肾小球滤过率（glomerular filtration rate,GFR）相关性,对D-D及Cys C对糖尿病患者早期肾损伤诊断进行方法学评价.结果 肾功能不全失代偿组肌酐（Cr）与正常对照组、肾功能正常组及肾功能不全代偿组比较均有统计学差异（P＜0.05）,肾功能不全代偿组、肾功能正常组及正常对照组3组组间Cr比较均无统计学差异（P＞0.05）;肾功能正常组及正常对照组D-D、Cys C比较均无统计学差异（P＞0.05）,其他任意两组比较均有统计学差异（P＜0.05）;D-D（r=-0.526,P＜0.05）及Cys C（r=-0.734,P＜0.05）与GFR均呈负相关,相关系数CysC高于D-D;方法学评价D-D及CysC有较高的灵敏度、特异度、符合率及约登指数.结论 D-D及Cys C在肾功能监测方面有较高的灵敏度,对糖尿病患者肾损伤早期诊断有重要的临床应用价值.     

地塞米松和维生素C对重症感染病人血清过氧化脂质变化的影响

本文报道４８例重症感染病人，在使用地塞米松或维生素Ｃ后血清过氧化脂质的变化。治疗前所有病人的血清ＬＰＯ均明显高于正常，当滴入地塞米松或维生素Ｃ后。ＬＰＯ值则下降，而对照组则持续升高，提示地塞米松和维生素Ｃ能阻止重症感染病人的脂质过氧化反应。     

原发性肺癌患者肾损害的临床分析

目的了解原发性肺癌患者。肾损害发生的原因及其预后。方法收集我院2007年6月至2008年12月出现肾损害的原发性肺癌患者52例,参照Ronco报道的标准判断肺癌患者出现肾损害的原因,以描述性统计学方法加以分析。结果肺癌相关性。肾损害19例,药物性肾损害23例,与肺癌并存的基础病引起的肾损害10例。所有患者中采用化疗23例,放疗17例,手术治疗3例。多数患者肾损害均有不同程度加重。肺癌相关性肾损害患者16例死亡,药物性肾损害患者22例死亡,与肺癌并存的基础病引起的肾损害9例死亡。结论原发性肺癌患者发生肾损害的原因依次为药物性肾损害、肺癌相关性肾损害和与肺癌并存的基础病引起的肾损害。其预后主要取决于肿瘤本身。     

维生素C 联合硫酸庆大霉素治疗复发性口腔溃疡的临床效果

目的 研究维生素C联合硫酸庆大霉素治疗复发性口腔溃疡的临床效果研究。方法 选取2019年8月-2021年6月于烟台市蓬莱中医医院治疗的86例复发性口腔溃疡患者为研究对象,根据随机数字表法分为常规组和联合组,各43例。常规组实施基础治疗,联合组实施维生素C联合硫酸庆大霉素治疗,比较两组临床治疗效果以及炎症因子水平。结果 联合组临床治疗总有效率为95.35%,高于常规组的79.07%（P ＜0.05）;两组治疗后hs-CRP、IL-6、IL-17以及TNF-α水平均低于治疗前,且联合组低于常规组（P＜0.05）。结论 维生素C联合硫酸庆大霉素用于复发性口腔溃疡患者,有利于提高临床治疗效果,降低机体口腔感染和炎症反应水平,值得在临床应用。     

Mechanisms of renal damage owing to infection

Urinary tract infection (UTI) is a common bacterial illness in children. It is known to be associated with an increased risk of permanent renal cell damage and scarring which may lead to generation of pathological conditions such as hypertension, pre-eclampsia during pregnancy, renal insufficiency, and end-stage kidney disease. The pathophysiology of renal scarring is still obscure, which makes the prevention of renal damage difficult. During acute infection, there are numerous factors that may contribute to tissue damage. Inflammatory responses are activated by host defense mechanisms as well as by specific bacterial virulence factors. Understanding of these complex mechanisms would be helpful to better identify children at high risk of developing renal scarring following UTI.     

维生素C注射液联合依托咪酯对膝关节置换术下肢缺血再灌注损伤患者氧化应激及炎症因子水平的影响

【摘要】目的：探讨维生素C注射液联合依托咪酯对膝关节置换术下肢缺血再灌注损伤患者氧化应激及炎症因子水平的影响。方法：纳入2020年6月至2021年12月于邯郸市中心医院行择期膝关节置换术的70例患者作为研究对象,按随机数表法将所有患者随机分配为观察组和对照组。对照组给予依托咪酯辅助诱导麻醉及麻醉维持,观察组在麻醉诱导前10 min、术中麻醉维持时、手术结束时、及术后12h分别予维生素C注射液0.5g。于术前（T0）、术毕麻醉停止前（T1）、术后1d（T2）、术后3d（T3）、术后5d（T4）这5个时间点分别抽取患者的外周静脉血,检测超氧化物歧化酶（SOD）的、丙二醛（MDA）、肿瘤坏死因子（TNF）-α和白介素（IL）-6的水平。结果：两组患者的年龄、性别分布、BMI、ASA分级、手术时间及止血带使用时间比较差异均无统计学意义（P均＞0.05）。两组患者术前（T0）和T1时间点的SOD和MDA水平比较无显著性差异（P＞0.05）;在T2、T3、T4时间点,观察组的SOD水平显著高于对照组,而MDA水平显著低于对照组（P＜0.05）。从T0到T4的SOD水平变化趋势为先降低,然后在T4点升高;从T0到T4的MDA水平变化趋势为先升高,然后在T4点降低。两组患者术前（T0）的TNF-α和IL-6水平比较均无显著性差异（P＞0.05）;在T1、T2、T3、T4时间点,观察组的TNF-α和IL-6水平显著低于对照组（P＜0.05）。从T0到T4的TNF-α和IL-6水平变化趋势为先升高,然后在T3点逐渐降低。两组患者的拔管时间和各不良反应的发生率比较均无统计学差异（P＞0.05）。两组患者术后1d和3d的疼痛评分比较差异有统计学意义,观察组显著低于对照组（P＜0.05）。结论：维生素C注射液联合依托咪酯可有效降低膝关节置换术下肢缺血再灌注损伤患者的氧化应激水平和炎症反应,降低术后疼痛程度。     

Vitamin E alleviates the oxidative stress of erythropoietin in uremic children on hemodialysis

The efficacy of combined therapy with recombinant human erythropoietin (rhEPO) and vitamin E versus rhEPO alone in the treatment of anemia was examined in children (n=10, aged 15.2±3.2 years) on chronic hemodialysis at the restart of rhEPO therapy after a 4-week interval. The results confirmed that rhEPO induced oxidative stress of the red blood cells as observed during the first rhEPO therapy. Vitamin E (15 mg/kg per day per os) was introduced after 2 weeks of rhEPO monotherapy, when the signs of acute oxidative stress appeared. The level of oxidized glutathione (GSSG) increased from 8.9±3.1 to 26.7±5.7 nmol/g hemoglobin (Hb) by that time. After 2 weeks of simultaneous vitamin E treatment, there was a significant difference in GSSG values compared with rhEPO monotherapy (10.1±3.9 vs. 56.7±15.8 nmol/g Hb, P<0.001). A considerable decrease was observed in the previously high ratio of GSSG/reduced glutathione (GSH), an indicator of oxidative stress, and the level of carboxyhemoglobin, indicating hemolysis. A significant increase in Hb and hematocrit (P<0.01) was achieved within 2 weeks of starting the combined therapy, while similar results occurred only at the 8th and 5th weeks without vitamin E. Antioxidant vitamin E supplementation improved the therapeutic effect of rhEPO in patients with chronic renal failure on hemodialysis. Received: 3 December 1998 / Revised: 20 April 1999 / Accepted: 20 April 1999