Influence of cardiopulmonary bypass on plasma lipid peroxides

In 22 patients who underwent cardiac surgery with cardiopulmonary bypass (CPB), we studied the influence of CPB on the level of lipid peroxides (LPO) in plasma by means of measuring the time course of plasma LPO level during and after CPB. We expressed LPO level, which was measured by thiobarbituric acid reaction, as the level of malondialdehyde. In our preliminary study, it was found necessary to correct the plasma LPO level diluted by priming fluids of CPB machine and the concentration of plasma protein was fitted for its correction. In the following study, we used the plasma LPO level corrected by the concentration of plasma protein. LPO were significantly decreased since the initiation of CPB (1.669 +/- 0.208 versus pre-CPB 1.785 +/- 0.158 log nmol MDA/gm protein, p less than 0.05) to the post CPB 30 minutes, except around 60 minutes after initiation of CPB (1.735 +/- 0.242 log nmol MDA/gm protein, p greater than 0.05). As the initial change (the values at 30 minutes after CPB initiation) may express the effect of CPB directly in this time course of LPO, we analyzed the initial change on different background factors. By ordinary analysis of the initial change, as to the effect of type of disease (congenital and acquired), LPO were decreased in the acquired group (1.617 +/- 0.197 versus pre-CPB 1.779 +/- 0.163 log nmol MDA/gm protein, p less than 0.05). At that time the acquired group was significantly different from the congenital group (1.799 +/- 0.191 versus pre-CPB 1.800 +/- 0.157 log nmol MDA/gm protein, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

A study on lipid peroxidation in neonates--(2). Perioperative changes in serum lipid peroxide and superoxide dismutase activity

Pre-, intra-, and post-operative changes in serum lipid peroxide: malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were studied in 10 neonates aged from 15 hours to 26 days. The results are summarized as follows: 1) Preoperative serum MDA levels were significantly lower than those of normal neonates. No significant difference was found between pre- and post-operative values, although much fluctuations were observed in neonates within 7 days of age. All the individual values returned to the normal range during the early postoperative period with different respiratory management. 2) Changes in serum SOD activity were similar to those in MDA values. The activity seemed to be higher and more sensitive to oxygen concentration in younger neonates, which may suggest the specific antioxidant properties of the neonates. 3) Postoperatively, serum MDA levels tended to increase following intravenous administration of lipid emulsion. 4) There was a positive correlation between the values of serum MDA and SOD activity, especially in neonates within 7 days of age.     

Increased lipid peroxides generation and calcium fluxes in hearts during reperfusion

To investigate the evidence for free radical generation and calcium influx as reperfusion injury, we studied the time course of lipid peroxides generation and calcium content in hearts during reperfusion. The study was performed in patients who had valve or coronary disease, and underwent open heart surgery. Lipid peroxides activity in plasma during reperfusion showed a significant (p less than 0.01) rise to a peak on 5 minutes of reperfusion (1.45 +/- 0.07 nmol/ml; mean +/- sem) compared to the level before reperfusion (1.37 +/- 0.07 nmol/ml) (n = 20). The lipid peroxides generation well correlated with aortic cross-clamp time (r = 0.6384, p less than 0.01). On the other hand, the atrial calcium content after 5-10 minutes of reperfusion was 118.5 +/- 14.9% of the level before cardiopulmonary bypass (n = 15), calcium/magnesium was 124.5 +/- 8.9% (p less than 0.05). That increase ratio well correlated with aortic crossclamp time (r = 0.5948, p less than 0.05). These results have produced evidence of increased oxidant activity and calcium influx in hearts during reperfusion. These results suggested that abnormal lipid peroxidation happened during reperfusion, and these peroxidation of the cell membrane might cause the membrane damage and then calcium influx.     

Nimodipine attenuates lipid peroxidation during the acute phase of head trauma in rats

Oxygen free radical-mediated lipid peroxidation is one of the major mechanisms of secondary damage in traumatic brain injury. We assessed the effects of nimodipine on lipid peroxidation 1 h after head trauma in rats. Nimodipine (1.5 μg/kg IV bolus injection) was given immediately after head trauma by either the carotid artery or the jugular vein. Placebo treated rats received saline by the same routes. Control rats received head trauma only. Sham-operated rats were the group without head trauma. Malondialdehyde (MDA), which is the end product of lipid peroxidation, was measured as an indicator of oxygen free radical formation in the brain tissue. The mean values for MDA in sham operated rats were 92.4±4.9 nanomoles/gram wet weight (nmol/gww) of brain tissue. In the control group, MDA content of the brain tissue was 120.8±9.4 nmol/gww. In placebo treated rats, the results were similar. In the groups receiving nimodipine via carotid artery or jugular vein, the mean values were 101.1±6.9 and 106.5±6.0 nmol/gww, respectively. These results indicate that nimodipine caused a significant decrease in lipid peroxidation when given in the acute phase of head trauma in rats. This occurred regardless of the route of injection. Received: 16 August 1999 / Accepted: 27 December 1999     

Effect of depletion of glucocorticoid receptor in the production of multiple organ failure during endotoxemia]

Endotoxin (20 mg/kg B.W.) was injected intravenously to control (n = 12) and glucocorticoid receptor (GR) depletion rat model (n = 13, in which more than 80 percent of GR were blocked with a potent GR antagonist RU486). Four hours after injection of endotoxin, the changes in serum acid phosphatase (ACP) activity, phospholipase A2 (PLA2) activity and lipid peroxide (LPO) level were determined. The results showed that all of the indices were increased in the control rats after endotoxin injection (ACP 17.6 +/- 1.9 U/dL, PLA2 325.6 +/- 99.1 U, and LPO 6.0 +/- 0.4 nmol MDA.ml-1), but they were increased to even higher levels in the rats injected with both RU486 and endotoxin (ACP 30.1 +/- 7.6 U/dL, PLA2 633.7 +/- 70.6 U, and LPO 8.2 +/- 1.1 nmol MDP.ml-1). Furthermore, after presented multiple organ damage pathologically. These results suggested that the glucocorticoid insufficiency caused by the decrease of GR after severe trauma or shock may exacerbate the damage of endotoxin to the organs, so much so that glucocorticoid insufficiency might result in multiple organ failure. This article also discussed problem of glucocorticoid treatment.     

Increased lipid peroxidation in patients on maintenance hemodialysis.

Lipid peroxidation products, lipid hydroperoxide and malonaldehyde were measured in the serum of patients on maintenance hemodialysis and compared with values obtained from a group of healthy controls. Dialysis patients had significantly elevated levels of lipid peroxidation products (12.9 +/- 1.9 vs. 9.3 +/- 1.3 nmol/ml, mean +/- SD, patients vs. controls, p less than 0.0001). In contrast, the serum transferrin level was significantly lower in the dialysis patients (217 +/- 71 vs. 290 +/- 50 mg/dl, patients vs. controls, p less than 0.0002). Compared to normal controls HDL cholesterol was lower (40 +/- 11 vs. 53 +/- 8, p less than 0.0001) and triglycerides were higher (206 +/- 103 vs. 142 +/- 64, p less than 0.007) in the patient group. The patient group was then divided on the basis of using polysulfone or cupraphane dialyzers. Patients using polysulfone dialyzers had lower levels of 2-thiobarbituric acid-reactive substances (12.3 +/- 0.9 vs. 13.6 +/- 2.1, polysulfone vs. cupraphane, p = 0.05), and higher transferrin concentrations (248 +/- 84 vs. 194 +/- 37, p = 0.03). Thus, in patients on maintenance hemodialysis there was evidence for accelerated lipid peroxidation. This abnormality was more marked in patients using traditional cupraphane dialyzers. The mechanism for this observation remains unclear.     

Early postburn lipid peroxidation: effect of ibuprofen and allopurinol

We measured lipid peroxidation of plasma, lung, and liver in anaesthetized sheep after third-degree burns involving 30% of total body surface. Animals were resuscitated to baseline filling pressures with lactated Ringer's solution and killed 10 hours after burn. Six sheep were pretreated with ibuprofen (12.5 mg/kg) and five with allopurinol (50 mg/kg). We used conjugated dienes and malondialdehyde as measures of lipid peroxidation. Circulating conjugated dienes increased from a baseline of 0.48 +/- 0.06 to 0.64 +/- 0.05 after burn, while protein-rich burn tissue lymph flow increased up to eightfold. We also noted a significant increase in lung tissue malondialdehyde from 45 +/- 4 to 60 +/- 6 nmol/gm and liver malondialdehyde from 110 +/- 20 to 271 +/- 34 nmol/gm along with increased tissue neutrophil sequestration. Ibuprofen attenuated lung-tissue malondialdehyde but had no effect on lung inflammation, circulating lipid peroxides or burn edema, indicating that ibuprofen most likely decreased O2 radical release in lung tissue by the already-sequestered neutrophils. Allopurinol, possibly via xanthine oxidase inhibition, markedly attenuated burn QL and circulating lipid peroxides and prevented all pulmonary lipid peroxidation and inflammation, indicating that release of oxidant from burn tissue was in part responsible for local burn edema, as well as distant inflammation and oxidant release, the latter most likely from complement activation. Neither antioxidant decreased lipid peroxidation in the liver; this indicates that its mechanism of production was different from that seen in burn tissue, in plasma, or in the lung. An ischemic event resulting from a selective decrease in splanchnic blood flow may be the cause of the liver changes.     

Systemic lipid peroxidation and inflammation induced by thermal injury persists into the post-resuscitation period

We determined the time course of the oxidant-induced systemic lipid peroxidation seen after burn injury. Twelve sheep were given a 15% of total body surface third-degree burn and monitored for 3 or 5 days. Circulating lipid peroxides were monitored by both malondialdehyde (MDA) and conjugated dienes (CD). Lung and liver tissue MDA was also measured and compared to controls. A significant but transient increase in circulating MDA and CD was noted several hours after burn. Venous plasma levels increased again 3-5 days postburn with onset of wound inflammation. Oxygen consumption, VO2, also increased by 35 +/- 12% at this time. Lung MDA, which increased to 64 +/- 5 from a control of 45 +/- 4 nMol/gm, at 12 hours after burn was still increased 3 days after injury. Marked lung inflammation was present early after injury and persisted for the 5-day study period. Liver MDA also increased from control value of 110 +/- 20 to 252 +/- 25 at 12 hours and remained increased over the 5-day period. Serum alkaline phosphatase was also increased. Burn biopsies revealed no infection to explain the ongoing lipid peroxidation process, i.e., bacterial content was less than 10(5) organisms/gram burn tissue. We conclude that an initial system lipid peroxidation occurs immediately after burn injury, and that this process continues well into the post-resuscitation period, corresponding in time with increased VO2, lung inflammation, and evidence of liver dysfunction. The ongoing oxidant changes with the presence of a burn may explain the accentuated organ dysfunction seen with an additional septic insult in burned patients.     

The effect of parenteral nutrition on biliary calcium and bilirubin

Recent studies have suggested that patients maintained on prolonged total parenteral nutrition (TPN) are at increased risk for gallstone formation. Animal and human data suggest that TPN causes calcium bilirubinate sludge and pigment gallstones. However, the effect of TPN on bile bilirubin and calcium concentrations has not previously been investigated. We, therefore, tested the hypothesis that TPN alters biliary bilirubin and calcium. Eight adult male prairie dogs received TPN (dextrose 15%, FreAmine III 4.25%, Intralipid 10%, insulin 25 U, electrolytes, and vitamins) at a rate of 80 cc/kg/day for 10 days. Eight additional animals maintained on a trace cholesterol diet served as controls. Gallbladder and hepatic bile samples were assayed for bilirubin and calcium. Cholesterol saturation index (CSI) and Rsa, a measure of gallbladder stasis, were also calculated. Calcium bilirubinate crystals were seen in gallbladder bile or wall scrapings of 7 of 8 TPN animals but in none of the controls (P less than 0.001). Animals that received TPN had bilirubin levels that were significantly higher in gallbladder bile (24.8 +/- 7.0 vs 5.1 +/- 0.9, P less than 0.05). Similarly, TPN animals had calcium levels that were significantly higher in gallbladder (30.0 +/- 3.6 vs 13.9 +/- 2.1, P less than 0.005) as well as hepatic (10.5 +/- 0.6 vs 7.4 +/- 0.6, P less than 0.005) bile. The Rsa values were also significantly lower (P less than 0.01) in TPN animals (0.57 +/- 0.07 vs 1.06 +/- 0.14). CSI, serum bilirubin, serum calcium, hematocrit, and reticulocyte counts did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis

Intravenous iron application to anemic patients on hemodialysis leads to an "oversaturation" of transferrin. As a result, non-transferrin-bound, redox-active iron might induce lipid peroxidation. To test the hypothesis that vitamin E attenuates lipid peroxidation in patients receiving 100 mg of iron(III) hydroxide sucrose complex intravenously during a hemodialysis session, 22 patients were investigated in a randomized cross-over design, either with or without a single oral dose of 1200 IU of all-rac-alpha-tocopheryl acetate taken 6 h before the hemodialysis session. Blood was drawn before and 30, 60, 90, 135, and 180 min after the start of the iron infusion, and areas under the curve (AUC0-180 min) of ratios of plasma malondialdehyde (MDA) to cholesterol and plasma total peroxides to cholesterol (two markers of lipid peroxidation) were determined as the outcome variables. At baseline of the session without vitamin E supplementation, plasma alpha-tocopherol concentrations (27.6 +/- 1.8 micromol/L) and ratios of alpha-tocopherol to cholesterol (5.88 +/- 1.09 mmol/mol) were normal, plasma MDA concentrations were above normal (1.20 +/- 0.28 micromol/ L), and bleomycin-detectable iron (BDI), indicating the presence of redox-active iron, was not detectable. Upon iron infusion, BDI and MDA concentrations increased significantly (P < 0.001). BDI concentrations explained the increase over baseline in MDA concentrations (MDA = 1.29 +/- 0.075 x BDI). Vitamin E supplementation, leading to a 68% increase in plasma alpha-tocopherol concentrations, significantly reduced the AUC0-180 min of MDA to cholesterol (P = 0.004) and peroxides to cholesterol (P = 0.002). These data demonstrate that a single oral dose of vitamin E attenuates lipid peroxidation in patients on hemodialysis receiving intravenous iron. Given that intravenous iron is applied repeatedly to patients on hemodialysis, this therapeutic approach may protect against oxidative stress-related degenerative disease in the long term.     

Topical flurbiprofen decreases burn wound-induced hypermetabolism and systemic lipid peroxidation

We studied the effect of the topical application of the nonsteroidal anti-inflammatory agent, flurbiprofen, on postburn hypermetabolism and systemic lipid peroxidation. Twelve sheep with a 15% total body surface third-degree burn were monitored over a 4-day postburn period. In six sheep, a single application of a 5% flurbiprofen cream was placed on the burn wound on day 3. Data were compared to both burned and nonburned controls (n = 6). All animals were killed on day 4. Oxygen consumption was increased at day 3 by 28% +/- 10% over the preburn value in all animals. Flurbiprofen significantly attenuated the increase in oxygen consumption, returning the value essentially to baseline by 12 hours after application. Lung and liver peroxidation, as measured by malondialdehyde, was significantly increased in the burned, nontreated sheep at day 4 from a control value of 45 +/- 9 and 110 +/- 12 to 60 +/- 6 and 310 +/- 71 nmol/gm tissue, respectively. In flurbiprofen-treated animals, values were 42 +/- 8 and 160 +/- 18 nmol/gm at day 4, significantly attenuated from burn alone. Protein-rich burn lymph flow remained fourfold increased in both groups, indicating a persistent increase in burn tissue vascular permeability, not modified by flurbiprofen. Burn wound biopsies revealed bacterial contents of less than 10(4) organisms/gram tissue in all animals. We conclude that topical flurbiprofen significantly decreases burn wound-induced systemic hypermetabolism and oxidant-induced lipid peroxidation seen at 3 days after burn injury, but does not attenuate the remaining local burn-wound vascular permeability.     

Effects of fluvastatin on plasma lipid abnormalities in hemodialysis patients with chronic renal failure

Fluvastatin, an HMG-CoA reductase inhibitor, was administered at a dosage of 20 mg/day for 24 weeks to 11 hemodialysis patients with a high plasma total cholesterol (TC) level (> or = 220 mg/dl). Serum lipids, apolipoprotein, and malondialdehyde (MDA) levels were measured every 12 weeks. After 24 weeks of fluvastatin administration, the TC level had decreased by 10.5% (238 +/- 15 mg/dl-->203 +/- 25 mg/dl), the low density lipoprotein cholesterol (LDL-C) level had decreased by 16.2% (142 +/- 32 mg/dl-->119 +/- 26 mg/dl), and the HDL-C level had increased by 23.4% (47 +/- 15 mg/dl-->58 +/- 19 mg/dl). These changes were statistically significant and resulted in a reduction of the atherogenic index (AI: TC-HDL-C/HDL-C). The triglyceride (TG) level did not change significantly. The apolipoprotein A1 level increased by 9.1% (121 +/- 22 mg/dl-->132 +/- 20 mg/dl) and the apolipoprotein B level decreased by 20.2% (114 +/- 25 mg/dl-->91 +/- 20 mg/dl). The MDA level also decreased significantly (1.16 +/- 0.92 nmol/ml-->0.58 +/- 0.38 nmol/ml). No particular side effects were observed during the 24 weeks of fluvastatin administration. In conclusion, fluvastatin may play an important role in preventing significant oxidative stress and was shown to be safe and effective in reducing the TC, LDL-C, MDA and AI levels in dialysis patients with hypercholesterolemia. The possibility that this improvement in the plasma lipid profile of dialysis patients may decrease atherogenic complications requires further investigation, including long-term clinical observations.     

The effects of sevoflurane and desflurane on lipid peroxidation during laparoscopic cholecystectomy

BACKGROUND AND OBJECTIVE: To compare the effects of sevoflurane and desflurane anaesthesia on lipid peroxidation. METHODS: We studied 40 healthy patients undergoing elective laparoscopic cholecystectomy. Patients were randomly allocated to be anaesthetized either with sevoflurane (n = 20) or desflurane (n = 20). Anaesthesia was maintained with inspiratory concentrations of sevoflurane 1-1.5 MAC (n = 20) or desflurane (n = 20). Samples were taken for plasma malondialdehyde and superoxide dismutase assays before induction of anaesthesia, before skin incision and at the end of surgery. Alveolar cell samples were obtained from the lungs using the technique of protective blind bronchoalveolar lavage, after induction of anaesthesia and at the end of surgery for malondialdehyde and superoxide dismutase concentrations. RESULTS: Plasma malondialdehyde increased more after the administration of desflurane than after sevoflurane: after induction 5.9 +/- 0.6 nmol mL(-1) for desflurane vs. 3.8 +/- 0.5 nmol L(-1) for sevoflurane (P < 0.001); at the end of the surgery: 6.7 +/- 0.4 nmol mL(-1) for desflurane vs. 4.2 +/- 0.3 nmol mL(-1) for sevoflurane (P < 0.001). There was a small but significant increase in plasma superoxide dismutase concentration after desflurane--from 24.2 +/- 1.2 to 24.9 +/- 0.9 U mL(-1) after induction and 25 +/- 1 U mL(-1) at the end of the surgery (P < 0.01)--but no increase with sevoflurane. Malondialdehyde concentrations increased significantly in the cells obtained by protective blind bronchoalveolar lavage at the end of surgery in the desflurane group (from 0.3 +/- 0.1 to 1.7 +/- 0.2 nmol mL(-1) (P < 0.001)), but not in the sevoflurane group. There were no significant differences between the two anaesthetics in the amounts of superoxide dismutase in the samples obtained by protective blind bronchoalveolar lavage. CONCLUSIONS: Desflurane may cause more systemic and regional lipid peroxidation than sevoflurane during laparoscopic cholecystectomy in healthy human beings.     

Carnitine status of pediatric patients on continuous ambulatory peritoneal dialysis

Plasma carnitine and the effect of oral carnitine supplementation on serum triglycerides was studied in 12 pediatric patients receiving continuous ambulatory peritoneal dialysis (CAPD). Baseline evaluation of all patients included plasma carnitine and serum triglyceride values. Following randomization into two groups, only group 2 patients received oral L-carnitine supplementation, 100 mg/kg/day, for 2 months. The initial laboratory evaluation was repeated at the conclusion of the study. Plasma carnitine values were also determined from a control population. Mean baseline plasma carnitine concentrations of group 1 (39.8 +/- 8.0 nmol/ml) and group 2 (45.2 +/- 10.3 nmol/ml) patients were not significantly different from each other or from the control population. Serum triglyceride values were elevated in both groups (group 1 - 206.5 +/- 100.0 mg/dl; group 2 - 279.3 +/- 74.5 mg/dl). After 2 months, the mean plasma carnitine concentration of group 2 patients increased to 147.7 +/- 84.1 nmol/ml, significantly greater than the value of group 1, 32.8 +/- 8.0 nmol/ml (p less than 0.004). However, no significant change in the serum triglyceride level was noted in either group. We conclude that the plasma carnitine status of pediatric patients receiving CAPD is normal and that oral carnitine supplementation does not lead to the resolution of hypertriglyceridemia.     

Propofol attenuates formation of lipid peroxides in tourniquet-induced ischaemia-reperfusion injury

We studied 20 adult ASA I patients undergoing elective peripheral surgery allocated randomly to one of two groups. In the propofol group (n = 9) anaesthesia was induced with propofol and fentanyl followed by continuous infusion of propofol. In the control group (n = 11), after induction of anaesthesia with thiopentone and fentanyl, anaesthesia was maintained with isoflurane. Concentrations of lipid peroxides in both plasma and muscle tissue samples were measured as thiobarbituric acid- reacting substances (TBARS). Plasma TBARS concentrations increased significantly in the control group at 1, 5, 15, 30 and 45 min after release of the tourniquet to mean 1.83 (SD 0.13), 2.00 (0.12), 2.25 (0.14), 2.30 (0.12) and 2.41 (0.14) mumol litre-1, respectively, compared with pre-reperfusion values (1.64 (0.14) mumol litre-1). In the propofol group this was significant only at 30 min (1.85 (0.03) vs 1.74 (0.04) mumol litre-1). TBARS concentrations of reperfused muscle tissue were significantly higher than pre-reperfusion concentrations in the control group (70.30(10.06) vs 52.13 (5.73) nmol/g wet tissue). We conclude that propofol attenuated ischaemia-reperfusion-induced lipid peroxidation in the therapeutic doses used in anaesthesia.      

The effect of calcitonin-gene-related peptide on acute ischemia-reperfusion renal injury: ultrastructural and membrane lipid peroxidation studies.

It is well accepted that postischemic reperfusion promotes functional and morphological impairment which may be related to oxygen free-radical-mediated membrane damage. A new purified bioactive compound, calcitonin-gene-related peptide (CGRP), is known to be not only a potent vasodilator but also a cytoprotective agent. This study was designed to observe whether CGRP has a protective effect on the ischemic kidney. Male Sprague-Dawley rats were subjected to a 45-min period of renal ischemia followed by 60 min of reperfusion. At the beginning of the reperfusion, 12 rats were given intravenous saline and served as controls whereas 5 rats were given CGRP, 10 micrograms/kg intravenously. After reperfusion the kidneys were removed for light- and electronmicroscopy, and the lipid peroxidation product malonaldehyde (MDA) was assayed by thiobarbituric acid (TBA) colorimetry. The results demonstrated that the serum creatinine (Scr) and renal MDA content in the CGRP group were significantly lower than those in the control group. The mean values for Scr were 0.75 +/- 0.09 vs 0.93 +/- 0.05 mg/dL or 62.8 +/- 9.7 vs 82.2 +/- 4.4 mumol/L (p less than 0.05), respectively; while the mean values for MDA were 18.71 +/- 2.13 vs 30.32 +/- 1.78 nmol/100 mg (ww) (p greater than 0.05), respectively. The same signals of free radicals in the ischemic-reperfused kidney with or without CGRP were found by electron spin resonance. Morphological studies demonstrated that the treatment with CGRP ameliorated the ischemic-reperfusion injury to both renal brush borders and mitochondria. The results showed that CGRP has a protective action on ischemia-reperfusion renal injury by decreasing lipid peroxidation of membranes and suggest that it may be a beneficial agent for therapy of acute renal failure.     

Smoking is associated with alterations of blood thiol-group related antioxidants in patients on hemodialysis

Cardiovascular disease is the major complication and cause of mortality in the dialysis population, accounting for about 40% of deaths. Oxidative stress has been strongly implicated in the pathogenesis of these events. As patients in end-stage renal disease (ESRD) are in a state of elevated free radical activity, the aim of the present study was to investigate the negative impact of smoking in 45 male hemodialysis (HD) patients. These patients, who were 40-85 years of age (mean age 60.9 +/- 13.3 years), had been on hemodialysis for at least 12 months before participating in this study. Fasting blood sampling for serum lipid, albumin, urate, lipid peroxides total blood glutathione (tGSH), non-GSH free sulfhydryl compounds (non-GSH fSH), plasma glutathione peroxidase (pGSHPx), erythrocytes glutathione peroxidase (rGSHPx), plasma glutathione S-transferase (pGST) and erythrocytes glutathione S-transferase (rGST) were determined. Our study showed that the plasma malonyldialdehyde (MDA) concentration was significantly higher in HD patients who smoked than in those who were non- smokers (1.99 +/- 0.53 vs. 1.55 +/- 0.46 nmol/ml, p = 0.008). No association was found between levels of MDA in smokers and BMI, serum cholesterol and triglycerides and smoking index. We also found that the circulating plasma levels of tGSH and non-GSH fSH was lower in the HD patients who smoked (tGSH 164.9 +/- 41.5 vs. 203.4 +/- 45.3 microg/ml; fSH 271.1 +/- 55.8 vs. 308.8 +/- 46.7 microg/ml; p < 0.05 and p < 0.001, respectively). There were no significant differences in the plasma levels of uric acid, pGSHPx, rGSHPx, pGST, rGST, albumin, and age between the 2 groups. Partial correlation analysis of the plasma levels of the measured antioxidants and the smoking index revealed a negative correlation between the plasma levels of tGSH and smoking index (r = -0.62, p < 0.003). Similarly, the plasma levels of tGSH was found negatively correlated with the levels of plasma MDA (r = -0.32, p < 0.05) of the HD patients. In conclusion, our data suggest that cigarette smoking has a negative impact on plasma-circulating products of lipid peroxidation in HD patients. The lower blood levels of the tGSH and non-GSH fSH in HD patients who smoked suggests that these patients may be more susceptible to oxidative damage caused by smoking.     

Effect of endotoxin and a burn injury on lung and liver lipid peroxidation and catalase activity

Both endotoxin and a burn alone produce oxidant-induced tissue lipid peroxidation. The endotoxin response is due in large part to hydrogen peroxide. The combination of endotoxin after a burn results in an increased liver, but not lung, oxidant injury. Our purpose was to determine whether the burn oxidant injury inactivated endogenous liver tissue catalase, thereby amplifying a subsequent H2O2 insult. Twenty-six adult sheep were studied. Twelve sheep had a 15% TBS burn. Tissue catalase activity, measured in lung and liver 3 days postburn, was significantly decreased from a control of 3.58 +/- 1.8 and 193 +/- 63, respectively, to 1.72 +/- 0.63 and 148 +/- 33 k(sec-1)/0.5 gram tissue. The addition of endotoxin 3 days postburn resulted in an increase in liver malondialdehyde, MDA, a measure of lipid peroxidation, from a control of 110 +/- 80 to 450 +/- 54 nmol/gram tissue. This value was significantly greater than the 210 +/- 80 nmol/gram tissue seen after endotoxin alone. Lung tissue MDA with burn and endotoxin was 65 +/- 8 compared to 42 +/- 7 for control and 80 +/- 6 nmol/gram for endotoxin alone. We conclude that a decrease in liver catalase activity occurs after a burn. The decrease corresponds to an accentuated oxidant-induced lipid peroxidation after an added endotoxin insult where H2O2 is known to be an etiologic agent. The catalase activity also decreases in postburn lung, but accentuated lung damage was not seen, indicating a variable tissue response from the burn-induced decrease in antioxidant activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

N-acetylcysteine reduces malondialdehyde levels in chronic hemodialysis patients--a pilot study

BACKGROUND: Oxidative stress has been implicated in the development of endothelial damage in hemodialysis (HD). We have assessed the effects of N-acetylcysteine (NAC), a compound with antioxidant effects, on malondialdehyde (MDA), a marker of oxidative stress on lipid peroxidation. METHODS: A clinical trial was conducted in which 24 chronic HD patients were divided into 2 groups according to gender, age, time on HD and cause of renal failure. The NAC group (n = 12) received 600 mg of NAC twice a day for 30 days. The remaining patients constituted the control group (n = 12). MDA levels were measured pre- and post-dialysis at the beginning of the study (baseline) and on day 30 (30 days). RESULTS: Baseline pre- and post-dialysis MDA levels were not different between both groups and were above normal values. A significant decrease was found in the NAC group when either pre- or post-dialysis MDA levels were compared to the corresponding control group levels on day 30 (pre-dialysis NAC vs control group 3.01 +/- 0.6 vs 4.5 +/- 0.73 micromol/l, p < 0.0001, post-dialysis NAC vs control group 2.76 +/- 0.5 vs 4.39 +/- 0.7 micromol/l, p < 0.0001). Only in the NAC group were pre-dialysis MDA 30-day levels different from pre-dialysis baseline levels (3.01 +/- 0.6 vs 5.07 +/- 1.6 micromol/l, p < 0.002). Post-dialysis MDA 30-day concentrations were significantly lower than post-dialysis MDA baseline levels (2.76 +/- 0.5 vs 4.32 +/- 0.7 micromol/l, p < 0.002) and pre-dialysis MDA 30-day measurements (2.76 +/- 0.5 vs 3.01 +/- 0.6 micromol/l, p < 0.011). CONCLUSIONS: MDA levels are elevated in chronic HD patients and are not significantly reduced by HD. NAC significantly reduces malondialdehyde levels in chronic HD patients.     

Melatonin, a pineal hormone with antioxidant property, protects against gentamicin-induced nephrotoxicity in rats

The present study investigated the effects of melatonin, an antioxidant, on gentamicin-induced nephrotoxicity in rats. Melatonin (5 mg/kg p.o.) was used 3 days before and 8 days simultaneously with gentamicin (80 mg/kg i.p.) Saline-treated animals served as controls. Determinations of urinary creatinine, N-acetyl-beta-D-glucosaminidase, glucose, protein, blood urea, serum creatinine, plasma and kidney tissue malondialdehyde (MDA), and antioxidant enzyme levels in kidney tissue were done after 8 days of gentamicin treatment. The kidneys were also examined for morphological changes using histological techniques. Gentamicin caused nephrotoxicity as evidenced by marked elevation in blood urea and serum creatinine. Mean blood urea and serum creatinine levels were 289+/-50, and 2.5+/-0.5 mg/dl, respectively, in rats treated with gentamicin. Melatonin significantly protected the rats from gentamicin-induced nephrotoxicity; blood urea and serum creatinine levels were 23+/-2.7 and 0.88+/-0.19 mg/dl, respectively. The creatinine clearance was decreased with gentamicin treatment (0.048+/- 0.007 ml/min) as compared with controls (0.41+/-0.08 ml/h/kg). In rats treated with melatonin plus gentamicin, the creatinine clearance was similar to controls (0.41+/-0.08 ml/h/kg). The product of lipid peroxidation (MDA) was markedly increased in plasma (2.10+/-0.15 nmol) and kidney tissue (8.87+/-3.2 nmol/mg protein) with gentamicin treatment. Melatonin prevented the gentamicin-induced rise in plasma MDA (1.03+/-0.27 nmol) and kidney tissue MDA (2.57+/-0.87 nmol/mg protein). An increased excretion of urinary N-acetyl-beta-D-glucosaminidase, glucose, and protein by gentamicin was also prevented by melatonin. Kidneys from gentamicin-treated rats showed tubular epithelial loss with intense granular degeneration involving more than 50% of renal cortex, while there were findings comparable to controls in melatonin plus gentamicin treated rats. The present study indicates that melatonin significantly protects against gentamicin-induced renal toxicity in Wistar rats.