Chronic hemodialysis (HD) patients manifest anemia and atherosclerosis with associated oxidative stress. We explored whether intravenous infusion of vitamin C (VC) and/or use of vitamin E (VE)-coated dialysis membrane could palliate HD-evoked oxidative stress. Eighty patients undergoing chronic HD were enrolled and randomly assigned into four groups: HD with intravenous VC (n=20), HD with VE-coated dialyzer (n=20), HD with both (n=20), and HD with neither (n=20). We evaluated oxidative stress in blood and plasma, erythrocyte methemoglobin/ferricyanide reductase (red blood cells (RBC)-MFR) activity, plasma methemoglobin, and pro-inflammatory cytokines in these patients. All patients showed marked increases (14-fold) in blood reactive oxygen species (ROS) after HD. The types of ROS were mostly hydrogen peroxide, and in lesser amounts, O2*- and HOCl. HD resulted in decreased plasma VC, total antioxidant status, and RBC-MFR activity and increased plasma and erythrocyte levels of phosphatidylcholine hydroperoxide (PCOOH) and methemoglobin. Intravenous VC significantly palliated HD-induced oxidative stress, plasma and RBC levels of PCOOH, and plasma methemoglobin levels and preserved RBC-MFR activity. The VE-coated dialyzer effectively prevented RBCs from oxidative stress, although it showed a partial effect on the reduction of total ROS activity in whole blood. In conclusion, intravenous VC plus a VE-coated dialyzer is effective in palliating HD-evoked oxidative stress, as indicated by hemolysis and lipid peroxidation, and by overexpression of proinflammation cytokines in HD patients. Using VE-coated dialyzer per se is, however, effective in reducing lipid peroxidation and oxidative damage to RBCs.

Objective To evaluate the possible role of free radicals in nephrolithiasis in rats induced by ethylene glycol, and to examine the correlation between the urinary enzymes N-acetyl-b-glucosaminidase (NAG), b-galactosidase (GAL) and neutral endopeptidase (NEP), and free radical production. Materials and methods Hyperoxaluria was produced in male Wistar rats by adding ethylene glycol to their drinking water. After 7, 21 and 42 days of treatment, urinary oxalate, creatinine clearance and urinary enzymes (NAG, GAL and NEP) were measured. The nitroblue tetrazolium perfusion method was used to locate the sites of free-radical production. Ultrasensitive chemiluminescence was used to directly measure the production of reactive oxygen species (ROS) in vivo. Vitamin E and potassium citrate were fed to rats, in addition to ethylene glycol, to assess their effects on free radical production.Results Urinary oxalate increased signi®cantly and was associated with an increase in NAG and GAL at all sample times. However, urinary NEP activity was unchanged on day 7, although there was four times as much NEP on days 21 and 42 than in the control groups. Formazan particles in the renal cortex were scored as 3+ to 4+ in rats treated for 7 days with ethylene glycol. Blood ROS levels were also higher in this group than in the controls (P<0.01). After vitamin E and potassium citrate treatment, blood ROS levels were lower than in rats treated with ethylene glycol alone. Conclusion Free radicals may be produced in the early stages of nephrolithiasis in rats fed with ethylene glycol. Free radicals occurred mainly in blood and might be associated with NEP inactivation.

IntroductionFluid resuscitation is an indispensable procedure in the acute management of hemorrhagic shock for restoring tissue perfusion, particularly microcirculation in splanchnic organs. Resuscitation fluids include crystalloids, hypertonic saline (HTS), and synthetic colloids, and their selection affects the recovery of microcirculatory blood flow and reactive oxygen species (ROS) formation, which is often evident in the kidney, following reperfusion. In this study, the effects of acute resuscitation with 0.9 % saline (NS), 3 % HTS, 4 % succinylated gelatin (GEL), and 6 % hydroxyethyl starch (HES) 130/0.4 were compared in a hemorrhagic shock rat model to analyze restoration of microcirculation among various splanchnic organs and the gracilis muscle and reperfusion-induced renal ROS formation.MethodsA total of 96 male Wistar rats were subjected to sham operation (sham group), hemorrhagic shock (control group), and resuscitation with NS, HTS, GEL and HES. Two hours after resuscitation, changes in the mean arterial pressure (MAP), serum lactate level and the microcirculatory blood flow among various splanchnic organs, namely the liver, kidney, and intestine (mucosa, serosal muscular layer, and Peyer’s patch), and the gracilis muscle, were compared using laser speckle contrast imaging. Renal ROS formation after reperfusion was investigated using an enhanced in vivo chemiluminescence (CL) method.ResultsMicrocirculatory blood flow was less severely affected by hemorrhaging in the liver and gracilis muscle. Impairment of microcirculation in the kidney was restored in all resuscitation groups. Resuscitation in the NS group failed to restore intestinal microcirculation. Resuscitation in the HTS, GEL, and HES groups restored intestinal microcirculatory blood flow. By comparison, fluid resuscitation restored hemorrhagic shock-induced hypotension and decreased lactatemia in all resuscitation groups. Reperfusion-induced in vivo renal ROS formation was significantly higher in the GEL and HES groups than in the other groups.ConclusionAlthough fluid resuscitation with NS restored the MAP and decreased lactatemia following hemorrhagic shock, intestinal microcirculation was restored only by other volume expanders, namely 3 % HTS, GEL, and HES. However, reperfusion-induced renal ROS formation was significantly higher when synthetic colloids were used.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-1135-y) contains supplementary material, which is available to authorized users.

Renal responses to renal sensory receptor activation were examined in rats after 1 and 4 wk of common bile duct ligation (CBDL). Compared with sham-operated rats (Sham), urine and sodium excretion after acute saline loading was significantly reduced at both times after CBDL. The blunted excretory responses in CBDL rats, accompanied by less activation of afferent renal nerve activity (ARNA), were already apparent at 1 wk and became severe at 4 wk. The defect in ARNA activation in CBDL rats was further studied using specific stimuli to activate renal sensory receptors. Graded increases in intrapelvic pressure or renal pelvic perfusion of substance P (SP) elicited an increase in ARNA in Sham rats, these responses being temporally attenuated in CBDL rats. Despite no significant change in renal pelvic SP release, no renorenal reflex was demonstrable in 4-wk CBDL rats. Immunoblotting showed that expression of renal pelvic neurokinin 1 (NK-1) receptors was 32 and 47% lower in 1- and 4-wk CBDL rats, respectively, than in Sham rats, this decrease correlating well with plasma SP levels. The quantitative real-time RT-PCR showed similar levels of NK-1 receptor mRNA in the renal pelvis in the Sham and 4-wk CBDL groups. We conclude that impairment of renal excretory and sensory responses increases with the duration of cirrhosis. An impaired renorenal reflex in cirrhotic rats is involved in the defective activation of the renal sensory receptors could be due, in part, to the low expression of NK-1 receptors, which is dependent on the duration of CBDL. The decrease in NK-1 receptor protein levels is not due to a decrease in mRNA levels.

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