Comparative aspects of plasma antioxidant status in sheep and goats, and the influence of experimental abomasal nematode infection.

This paper provides, for the first time, comparative data on the plasma antioxidant status of two ruminant species, namely sheep and goats. In addition, the influence of experimental infection with Teladorsagia circumcincta on antioxidant status in the same two species is compared and contrasted. In general terms, antioxidant status was significantly higher in uninfected kids than in lambs. Differences in protein sulphydryl groups and vitamin E concentrations were particularly noteworthy; trends were similar, however, for albumin, vitamin A and total antioxidant capacity (TAC). Parasitological results, based on worm burden, faecal egg counts and peripheral blood eosinophil numbers, confirmed that goat kids were more susceptible than lambs to experimental T. circumcincta infection. "Trickle infection" had a variable impact on both total and individual antioxidant status; particularly during the early weeks, the trend was for reduced values in lambs and increased values in kids, as compared with uninfected controls. Subsequent challenge infection was associated with a transient decrease in TAC and albumin in trickle-infected animals of both species, and in appropriate control animals. The observed differences in plasma antioxidant capacity between sheep and goats may have important implications in terms of the comparative resilience of sheep and goats to parasite infection.

Homocysteine and B-group vitamins in renal transplant patients.

Increased plasma homocysteine is an independent risk factor for cardiovascular disease. We have investigated homocysteine and B-group vitamin levels in renal transplant patients. Fasting blood was collected from 55 renal transplant recipients with good renal function and 32 age/sex matched control subjects. Total homocysteine was increased in transplant recipients in comparison to controls (10.9+/-1.5 vs. 6.7+/-1.3 micromol/l, P < 0.001). There was no difference in homocysteine between patients receiving cyclosporin (n = 39, homocysteine 11.0+/-1.5 micromol/l) and patients receiving prednisolone + azathioprine (n = 16, 10.8+/-1.6 micromol/l, mean+/-S.D.), although there was a significant correlation between homocysteine and serum cyclosporin concentration in the sub-group of patients receiving that immunosuppressive regimen (r = 0.42, P < 0.05). Levels of B-group vitamins were similar in patients and controls. Plasma homocysteine is increased in renal transplant recipients even in the presence of minor degrees of renal impairment and normal levels of B-group vitamins.

Effect of hemodialysis on total antioxidant capacity and serum antioxidants in patients with chronic renal failure.

Cardiovascular disease is the major cause of mortality in patients receiving hemodialysis for chronic renal failure. Increased lipid peroxidation and depletion of chain-breaking antioxidants may contribute to increased risk of atherosclerosis. We have therefore assessed the effect of a single episode of hemodialysis on antioxidant status in 22 patients and control subjects. Overall, total antioxidant capacity of serum was increased in dialysis patients, but there was a marked reduction after hemodialysis [571 +/- 31 vs 342 +/- 22 mumol/L Trolox (water-soluble vitamin E analog) equivalents, P < 0.001]. The increase in total antioxidant capacity before hemodialysis was almost entirely due to relatively high serum urate. Among individual chain-breaking antioxidants, dialysis led to a decrease in urate (398 +/- 15 vs 136 +/- 12 mumol/L, P < 0.001), ascorbate (10.5 +/- 1.7 vs 5.9 +/- 1.0 mumol/L, P < 0.01), and lipid-corrected tocopherol (4.70 +/- 0.56 vs 4.26 +/- 0.39 mumol/mmol cholesterol, P < 0.05). Protein thiol groups increased after dialysis (328 +/- 16 vs 422 +/- 22 mumol/L, P < 0.001), whereas albumin remained unchanged (40.1 +/- 1.1 vs 41.0 +/- 1.6 g/L, not significant). Although total antioxidant capacity of serum is increased in hemodialysis patients, depletion of key chain-breaking antioxidants may lead to accelerated atherogenesis.

The effects of desferrioxamine and ascorbate on oxidative stress in the streptozotocin diabetic rat.

Oxidative stress and protein glycation are closely related processes that may contribute to the development of complications in diabetes mellitus. Treatment with antioxidants could protect against these processes at a biochemical level, and we have therefore investigated the effects of ascorbate and desferrioxamine treatment in the streptozotocin diabetic rat. Diabetic animals were given ascorbate 1 g/l in drinking water or desferrioxamine 6 mg/kg/day by subcutaneous injection and were killed after 6 weeks. In diabetic animals, oxidative stress was increased as shown by increased levels of conjugated dienes (CD) in plasma and malondialdehyde (MDA) in plasma, erythrocyte membranes, and urine. In addition, there was depletion of the nutritional antioxidants ascorbate, alpha-tocopherol, and retinol. Insulin treatment returned all of these parameters to normal. Ascorbate supplementation or desferrioxamine treatment alone failed to reduce oxidative stress, but a combination of both interventions restored MDA, CD, and antioxidant vitamins to control values. Both ascorbate and desferrioxamine also reduced HbA1c and glycated albumin levels. Treatment with antioxidants can reduce both oxidative stress and protein glycation and may help to reduce the risk of developing diabetic complications. However, ascorbate can have both prooxidant and antioxidant effects in vivo, and its use in pharmacological doses should be approached with caution.

Oxidative stress in haemodialysis.

Patients with chronic renal failure, including those receiving regular long-term haemodialysis, have a high incidence of premature cardiovascular disease. Oxidative stress, which occurs when there is excessive free-radical production or low antioxidant levels, has recently been implicated as a causative factor in atherogenesis. The aim of this study was to determine if chronic renal failure and haemodialysis were associated with increased oxidative stress. Serum malondialdehyde was measured as a marker of lipid peroxidation in 15 patients with conservatively managed chronic renal failure (CRF), 15 patients with CRF undergoing regular haemodialysis and 15 healthy controls. Selenium, glutathione peroxidase and antioxidant vitamins were also measured. Malondialdehyde was elevated in dialysis patients in comparison to CRF and control groups (dialysis 1.16 +/- 0.08 mumol/l, CRF 0.94 +/- 0.07, controls 0.66 +/- 0.10). Antioxidants, including vitamin C, selenium and glutathione peroxidase, were decreased in dialysis patients and to a lesser extent in the CRF group (vitamin C-dialysis 16.43 +/- 3.76 mumol/l, CRF 34.5 +/- 8.6, controls 56.11 +/- 7.41; selenium-dialysis 0.77 +/- 0.07 mumol/l, CRF 0.69 +/- 0.06, controls 1.09 +/- 0.06: glutathione peroxidase-dialysis 101 +/- 5 U/l, CRF 160 +/- 11, controls 290 +/- 10). These findings indicate oxidative stress in patients with CRF which is further exacerbated by haemodialysis, as evidenced by increased lipid peroxidation and low antioxidant levels. This stress may play a role in the development of atherosclerosis in these groups.

Reduction of free radical generation minimises lower limb swelling following femoropopliteal bypass surgery.

Oxygen-derived free radicals have been implicated as contributors to the development of lower limb oedema observed after femoropopliteal bypass grafting. This study investigates the occurrence of free radical-induced lipid peroxidation after this operation and the possible effects of allopurinol (xanthine oxidase inhibitor) in reducing free radical injury in order to minimise lower leg oedema. Twenty-nine patients undergoing femoropopliteal bypass surgery were randomised in a double blind fashion into two groups; those in one were given allopurinol 200 mg orally (n = 15) at 24 h and 2 h preoperatively and again at 24 h postoperatively, while those in the second group received a placebo (n = 14). Daily lower limb volume was calculated to assess swelling. Blood samples were taken from the femoral vein for measurements of malondialdehyde (MDA), an end product of lipid peroxidation, before the application of the femoral artery clamp, just prior to and immediately after clamp release, and at 20 minute intervals thereafter for 1 hour. The increase in lower limb volume in the placebo group was almost twice (8.9 +/- 1.6%) that of the allopurinol group (4.6 +/- 1%; p = 0.02). Six out of the 14 patients receiving placebo suffered swelling of 10% or more of original lower limb volume in comparison to only one out of 15 in those given allopurinol (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid peroxidation and antioxidant status following thrombolytic therapy for acute myocardial infarction.

We have investigated the timescale of increased lipid peroxidation following successful early thrombolytic therapy for acute myocardial infarction and report for the first time reciprocal changes in plasma chain-breaking antioxidants. Sixty-seven patients were recruited following a first acute myocardial infarction within 6 h of the onset of symptoms and received 70 or 100 mg of recombinant tissue plasminogen activator (Actilyse) as two intravenous bolus injections 30 min apart. Serial blood samples were taken before administration of thrombolytic therapy and after 30 min, 60 min, 90 min, 6 h and 24 h. Coronary artery patency was assessed at 90 min by coronary angiography. Malondialdehyde (MDA), a marker of lipid peroxidation, and the chain-breaking antioxidants alpha-tocopherol, retinol and ascorbate were measured by high performance liquid chromatography. When the coronary artery was patent there was an early rise in plasma MDA (time 0 0.91 +/- 0.05 mumol.l-1) with levels peaking at 90 min (1.02 +/- 0.06, P < 0.05) and returning to baseline by 6 h (0.85 +/- 0.06), accompanied by reciprocal decreases in alpha-tocopherol (time 0 7.13 +/- 0.34 mumol.mmol-1 cholesterol, 90 min 6.64 +/- 0.33, P < 0.05) and retinol (time 0 1.99 +/- 0.10 mumol.l-1, 90 min 1.81 +/- 0.08, P < 0.05). Ascorbate levels did not change significantly until 24 h (time 0 29.5 +/- 4.9 mumol.l-1, 24 h 22.6 +/- 4.4, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)