Oxidative stress and nutritional factors in hepatitis C virus-positive liver recipients, controls, and hepatitis C virus-positive nontransplant patients.

BACKGROUND: Hepatitis C virus (HCV) is the most common indication for liver transplantation, but HCV recurrence is frequent after 1 year and is associated with increased morbidity and mortality. Oxidative stress (OxS) is involved in the pathogenesis of HCV, but little is known about its presence prior to disease recurrence. AIM: To determine if at 6 months HCV-positive liver recipients (HCV-OLT) without recurrence were oxidatively stressed. METHODS: 33 HCV-OLTs, 12 controls, and 39 HCV-positive nontransplant patients (HCV-NTs). OxS was assessed by using commercial kits to measure liver lipid peroxidation (LPO) and antioxidant potential (AOP). Plasma vitamin E, retinol (HPLC), and vitamin C (spectrophotometry) were assessed. We collected Anthropometry and 3-day food records. We performed analysis by the Kruskal-Wallis test expressing data as mean values +/- standard errors of the mean. RESULT: Waist-hip ratio was higher in both HCV-OLTs and HCV-NTs compared to the controls. HCV-OLTs showed higher hepatic LPO (mumol malondialdehyde/g tissue) versus controls (1.4 +/- 0.20 vs 0.54 +/- 0.10; P = .010) and compared to HCV-NTs (0.98 +/- 0.17; P = .030). No significant differences were found among the groups regarding hepatic AOP. However, lower plasma AOP (micromols UEA) were observed in HCV-OLTs (0.07 +/- 0.008) versus controls (0.17 +/- .040; P = .021) or HCV-NTs (0.08 +/- 0.009; P = .015) versus controls. Plasma gamma-tocopherol was higher in HCV-OLTs and HCV-NTs compared to controls (P = .001). We observed lower vitamin A intake in HCV-OLTs compared with the other two groups (P = .001). CONCLUSIONS: HCV-OLTs without disease recurrence are oxidatively stressed compared with control and HCV-NTs. Future research is needed to determine the impact of this increased oxidative stress on HCV disease recurrence.

Hepatic lipid peroxidation and antioxidant micronutrients in hepatitis virus C liver recipients with and without disease recurrence.

BACKGROUND: Hepatitis C virus (HCV) reinfection after liver transplantation is universal and progresses to cirrhosis in 10% to 30% of patients. Several risk factors are associated with progression. Oxidative stress may be involved because it has a role in the pathogenesis of HCV. OBJECTIVE: To determine whether HCV liver recipients with disease recurrence are more oxidatively stressed than those with no recurrence. METHODS: Measurements were performed at 12 months posttransplantation, and in a subgroup of patients at 6 months. Liver lipid peroxidation (LPO), antioxidant potential, plasma vitamin E, retinol, and vitamin C were measured. Demographic data, pretransplantation viral load, anthropometry, and 3-day food records were also obtained. Data were log-transformed; analysis was performed using the independent t test, Pearson correlation, and multivariate regression analysis. RESULTS: Recipients of HCV livers with recurrence (n = 21) had higher liver LPO (mean [SEM] micromoles of malondialdehyde per gram of liver tissue, 1.66 [0.28]) vs those with no recurrence (n = 16; 0.88 [0.13]) (P = .02). A significant relationship was found between liver LPO and HCV recurrence, and this significance continued when accounting for pretransplantation viral load and donor age. Six patients with recurrence and 11 with no recurrence also had measurements obtained at 6 months posttransplantation. Those with recurrence at 12 months had significantly higher hepatic LPO at 6 months (1.86 [0.62]) compared with those with no recurrence (0.75 [0.14]) (P = .04). CONCLUSIONS: Recipients of HCV livers with recurrence are more oxidatively stressed at 6 and 12 months compared with those with no recurrence. Accounting for viral load and donor age, oxidative stress was independently associated with recurrence. More research is needed to confirm this association.

Oxidative stress and nutritional intakes in lung patients with bronchiolitis obliterans syndrome.

Survival after lung transplantation is limited by bronchiolitis obliterans syndrome (BOS). Oxidative stress (OxS) can be associated with BOS due to chronic inflammation. The type of fat and antioxidant intakes may also contribute to OxS. Our aim was to compare OxS and nutritional intakes in non-BOS versus various stages of BOS. Fifty-eight lung recipients with versus without BOS were prospectively classified as: non-BOS; BOS Op-1 (mild), and BOS 2-3 (severe). We measured nutritional intake and plasma vitamins A, C, and E. Among a subgroup of 37 patients, OxS was assessed by measuring lipid peroxidation (LPO micromol/L MDA) and oxidized glutathione (GSSG) in bronchoalveolar lavage BAL fluid (BALF). One-way analysis of variance was used to compare groups. Results are reported as mean values +/- standard errors of the mean. There was no significant difference in demographic features on time posttransplant among groups. Although there were comparable cell counts in BALF, severe BOS patients showed significantly higher BALF LPO concentrations when compared with milder stage of BOS or with non-BOS (P = .001, for both). Severe BOS recipients also displayed higher BALF GSSG concentrations compared to milder stage of BOS (P = .001) or non-BOS (P = .007). In conclusion, patients with severe BOS were more oxidatively stressed compared with mild and non-BOS recipients.

Metabolic bone disease in patients receiving home parenteral nutrition: a Canadian study and review.

BACKGROUND: Metabolic bone disease (MBD) is a significant complication in patients receiving long-term home parenteral nutrition (HPN). Pamidronate has been poorly studied in this population. We examine the prevalence and risk factors for MBD and examine changes in bone mineral density (BMD) after pamidronate administration. METHODS: First, a chart review of patients receiving HPN for >1 year was performed, and Pearson correlations were used to assess associations between MBD (defined as t score<-1) and risk factors. Second, the effect of IV pamidronate on BMD was studied prospectively in 11 HPN patients. Results were compared using a t-test. RESULTS: Charts were reviewed in 25 patients (15 F, 10 M): age, 56.9+/-3.1 years; body mass index (BMI), 21.2+/-0.57 kg/m2; months receiving HPN, 113.2+/-0.09; and days per week receiving HPN, 5.08+/-0.39. MBD was present in 33% of patients for the spine and hip and in 50% for the femoral neck; 24% had previous fractures. There was a significant negative correlation between the duration of HPN and BMD (r=-0.40) for all measurements. From those patients, 11 received IV pamidronate for a mean of 22.2+/-5.4 months. At baseline, their mean HPN treatment duration was 10.6+/-6.3 years. Overall, BMD results showed a trend toward improvement in the mean t score of the spine and hip postpamidronate therapy (pre, -3.1+/-0.75; post, -2.9+/-0.69; p=.07). After excluding 2 patients receiving corticosteroids, the mean t score of the spine showed significant improvement (prepamidronate -3.4+/-0.57 vs post-pamidronate -3.1+/-0.65, p=.036). CONCLUSIONS: In our HPN population, 76% had MBD and 24% had previous fractures. The results suggest that these patients may benefit from pamidronate. More studies are needed to assess the efficacy of pamidronate.

Effect of oral iron supplementation on oxidative stress and colonic inflammation in rats with induced colitis.

BACKGROUND: Iron supplementation may increase disease activity in ulcerative colitis, possibly through the production of reactive oxygen species from the Fenton reaction. AIM: To assess the effects of two doses of oral iron on intestinal inflammation and oxidative stress in experimental colitis. METHODS: Colitis was induced in rats by giving 5% dextran sulphate sodium in drinking water for 7 days. First, using a 2 x 2 factorial design, rats with or without dextran sulphate sodium received the regular diet or a diet containing iron 3%/kg diet. Second, rats with dextran sulphate sodium-induced colitis were supplemented with iron 0.3%/kg diet and compared with rats on dextran sulphate sodium and regular diet. The body weight change, histological scores, colon length, rectal bleeding, plasma and colonic lipid peroxides, colonic glutathione peroxidase and plasma vitamin E and C were measured. Faecal analysis for haem and total, free and ethylenediaminetetra-acetic acid-chelatable iron was also performed. RESULTS: Iron 3% and iron 0.3% increased the activity of dextran sulphate sodium-induced colitis, as demonstrated by higher histological scores, heavier rectal bleeding and further shortening of the colon. This was associated with increased lipid peroxidation and decreased antioxidant vitamins. Faecal iron available to the Fenton reaction was increased in a dose-dependent manner. CONCLUSIONS: Iron supplementation taken orally enhanced the activity of dextran sulphate sodium-induced colitis and is associated with an increase in oxidative stress.

Lipid peroxidation and plasma antioxidant micronutrients in Crohn disease.

BACKGROUND: In Crohn disease (CD), the increased production of reactive oxygen species from activated neutrophils may reduce plasma concentrations of antioxidant vitamins and result in increased oxidative stress. OBJECTIVE: We compared lipid peroxidation, a measure of reactive-oxygen-species production, and plasma antioxidant vitamin concentrations between CD patients and healthy control subjects. DESIGN: Thirty-seven nonsmoking CD patients (22 women and 15 men) were compared with an equal number of healthy control subjects who were matched by age, sex, and body mass index. In patients the mean CD activity index (CDAI) was 141.2 +/- 18.7 (range: 9.0-514), and 11 of 37 patients (30%) had a CDAI > or =150. Seventy-eight percent of patients were taking > or = 1 medication. Medication use by subjects included the following: 5-aminosalicylic acid (40% of subjects), antibiotics (22%), oral corticosteroids (30%), and immunosuppressants (19%). RESULTS: Lipid peroxidation as measured by breath pentane output (CD patients, 7.47 +/- 0.98 pmol x kg(-1) x min(-1); control subjects, 4.97 +/- 0.48 pmol x kg(-1) x min(-1); P < or = 0.025), breath ethane output (CD patients, 11.24 +/- 1.17 pmol x kg(-1) x min(-1); control subjects, 5.46 +/- 0.71 pmol x kg(-1) x min(-1); P < or = 0.0005) and F2-isoprostane (CD patients, 78.6 +/- 8.0 ng/L; control subjects, 60.6 +/- 3.7 ng/L; P < or = 0.047) were significantly higher in CD patients than in control subjects. Plasma antioxidant vitamins (ascorbic acid, alpha- and beta-carotene, lycopene, and beta-cryptoxanthin) were all significantly lower in CD patients than in control subjects. There were no significant differences in macro- and micronutrient intakes between groups. CONCLUSION: Patients with CD are oxidatively stressed, which was observed even though 70% of patients had a CDAI < or =150 and 78% of them were taking medications to treat CD.

Effect of iron supplementation on oxidative stress and intestinal inflammation in rats with acute colitis.

In this study, we investigated the effect of intraperitoneal iron dextran (100 mg/100 g body weight) on oxidative stress and intestinal inflammation in rats with acute colitis induced by 5% dextran sulfate sodium. In both colitis and healthy animals, disease activity index, crypt and inflammatory scores, colon length, plasma and colonic lipid peroxides, and plasma vitamins E, C, and retinol were assessed. The results showed that iron-supplemented groups had moderate iron deposition in the colonic submucosa and lamina propria. In the colitis group supplemented with iron, colon length was significantly shorter; disease activity index, crypt, and inflammatory scores and colonic lipid peroxides were significantly higher; and plasma alpha-tocopherol was significantly lower compared to the colitis group without iron supplementation. There was no intestinal inflammation and no significant increase in colonic lipid peroxides in healthy rats supplemented with iron. In conclusion, iron injection resulted in an increased oxidative stress and intestinal inflammation in rats with colitis but not in healthy rats.

Breath alkanes as a marker of oxidative stress in different clinical conditions.

We assessed oxidative stress in three different clinical conditions: smoking, human immunodeficiency virus (HIV) infection, and inflammatory bowel disease, using breath alkane output and other lipid peroxidation parameters such as plasma lipid peroxides (LPO) and malondialdehyde (MDA). Antioxidant micronutrients such as selenium, vitamin E, C, beta-carotene and carotenoids were also measured. Lipid peroxidation was significantly higher and antioxidant vitamins significantly lower in smokers compared to nonsmokers. Beta-carotene or vitamin E supplementation significantly reduced lipid peroxidation in that population. However, vitamin C supplementation had no effect. In HIV-infected subjects, lipid peroxidation parameters were also elevated and antioxidant vitamins reduced compared to seronegative controls. Vitamin E and C supplementation resulted in a significant decrease in lipid peroxidation with a trend toward a reduction in viral load. In patients with inflammatory bowel disease, breath alkane output was also significantly elevated when compared to healthy controls. A trial with vitamin E and C is underway. In conclusion, breath alkane output, plasma LPO and MDA are elevated in certain clinical conditions such as smoking, HIV infection, and inflammatory bowel disease. This is associated with lower levels of antioxidant micronutrients. Supplementation with antioxidant vitamins significantly reduced these lipid peroxidation parameters. The results suggest that these measures are good markers for lipid peroxidation.

Oxidative stress in smokers supplemented with vitamin C.

The ability of vitamin C supplement to influence lipid peroxidation and pulmonary function tests in healthy smokers was investigated. In this randomized double blind controlled trail, 56 smokers (S) received either 500 mg of vitamin C (C) or placebo (P) daily for 4 weeks. All completed the trial. Both groups were comparable and the number of cigarettes smoked were C: 14.2 +/- 1.8 and P: 18.3 +/- 2.0 pack-years. Plasma vitamin C concentrations increased significantly (p < 0.005) only in the group supplemented with vitamin C. Lipid peroxidation measured by breath pentane output (BPO) (C: 7.5 +/- 1.4 vs P: 7.0 +/- 1.3 pmol.kg-1.min-1) and plasma HPLC-separated malondialdehyde (MDA) (C: 0.58 +/- 0.05 vs P: 0.47 +/- 0.05 nmol.ml-1) were not significantly different between the 2 groups at baseline and did not change after four weeks of vitamin C supplementation (BPO: C: 5.3 +/- 0.9 vs P: 5.5 +/- 0.9 pmol.kg-1.min-1; HPLC-MDA: C: 0.50 +/- 0.07 vs P: 0.42 +/- 0.07 nmol.ml-1). No changes were detected in pulmonary function tests even in heavy smokers. Therefore, 4 week supplementation with 500 mg of vitamin C did not change lipid peroxidation indices and had no effect on pulmonary function tests.

Effects of vitamin E and C supplementation on oxidative stress and viral load in HIV-infected subjects.

OBJECTIVES: The HIV-infected population is known to be oxidatively stressed and deficient in antioxidant micronutrients. Since in vitro replication of HIV is increased with oxidative stress, this study assessed the effect of antioxidant vitamin supplementation on lipid peroxidation, a measure of oxidative stress, and viral load in humans. DESIGN: A randomized placebo-controlled, double-blind study. METHODS: Forty-nine HIV-positive patients were randomized to receive supplements of both DL-alpha-tocopherol acetate (800 IU daily) and vitamin C (1000 mg daily), or matched placebo, for 3 months. Plasma antioxidant micronutrient status, breath pentane output, plasma lipid peroxides, malondialdehyde and viral load were measured at baseline and at 3 months. New or recurrent infections for the 6-month period after study entry were also recorded. RESULTS: The vitamin group (n = 26) had an increase in plasma concentrations of alpha-tocopherol (P < 0.0005) and vitamin C (P < 0.005) and a reduction in lipid peroxidation measured by breath pentane (P < 0.025), plasma lipid peroxides (P < 0.01) and malondialdehyde (P < 0.0005) when compared with controls (n = 23). There was also a trend towards a reduction in viral load (mean +/- SD changes over 3 months, -0.45 +/- 0.39 versus +0.50 +/- 0.40 log10 copies/ml; P = 0.1; 95% confidence interval, -0.21 to -2.14). The number of infections reported was nine in the vitamin group and seven in the placebo group. CONCLUSION: Supplements of vitamin E and C reduce oxidative stress in HIV and produce a trend towards a reduction in viral load. This is worthy of larger clinical trials, especially in HIV-infected persons who cannot afford new combination therapies.

Oxidative stress and plasma antioxidant micronutrients in humans with HIV infection.

Increased lipid peroxidation induced by reactive oxygen species may play a role in the stimulation of HIV replication. In this study we compared lipid peroxidation indexes and plasma antioxidant micronutrients between 49 nonsmoking HIV-positive patients with no active opportunistic infection (25 asymptomatic and 24 with AIDS) and 15 age-matched seronegative control subjects. Breath-alkane output, plasma lipid peroxides, antioxidant vitamins, and trace elements were measured. Vitamin C (40.7 +/- 3.02 compared with 75.7 +/- 4.3 mumol/L, P < 0.005), alpha-tocopherol (22.52 +/- 1.18 compared with 26.61 +/- 2.60 mumol/L, P < 0.05), beta-carotene (0.23 +/- 0.04 compared with 0.38 +/- 0.04 mumol/L, P < 0.05), and selenium (0.37 +/- 0.05 compared with 0.85 +/- 0.09 mumol/L, P < 0.005) concentrations were significantly lower in the HIV-positive patients. Lipid peroxides (50.7 +/- 8.2 compared with 4.5 +/- 0.8 mumol/L, P < 0.005), breath pentane (9.05 +/- 1.23 compared with 6.06 +/- 0.56 pmol.kg-1.min-1, P < 0.05), and ethane output (28.1 +/- 3.41 compared with 11.42 +/- 0.55 pmol.kg-1.min-1, P < 0.05) were significantly higher in the HIV-positive patients. These results showed an increase in oxidative stress and a weakened antioxidant defense system in HIV-positive patients. Whether supplementation of antioxidant vitamins will reduce this oxidative stress is still unknown.

Lipid peroxidation during n-3 fatty acid and vitamin E supplementation in humans.

The purpose of this study was to investigate in healthy humans the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake, alone or in combination with dL-alpha-tocopherol acetate (vitamin E) supplements on lipid peroxidation. Eighty men were randomly assigned in a double-blind fashion to take daily for 6 wk either menhaden oil (6.26 g, n-3 fatty acids) or olive oil supplements with either vitamin E (900 IU) or its placebo. Antioxidant vitamins, phospholipid composition, malondialdehyde (MDA), and lipid peroxides were measured in the plasma at baseline and week 6. At the same time, breath alkane output was measured. Plasma alpha-tocopherol concentration increased in those receiving vitamin E (P < 0.0001). In those supplemented with n-3 fatty acids, EPA and DHA increased in plasma phospholipids (P < 0.0001) and plasma MDA and lipid peroxides increased (P < 0.001 and P < 0.05, respectively). Breath alkane output did not change significantly and vitamin E intake did not prevent the increase in lipid peroxidation during menhaden oil supplementation. The results demonstrate that supplementing the diet with n-3 fatty acids resulted in an increase in lipid peroxidation, as measured by plasma MDA release and lipid peroxide products, which was not suppressed by vitamin E supplementation.

Cecal infusion of nutrients improves nutritional status of rats.

The role of colonic fermentation in providing energy was investigated in rats with small bowel transection (T) or 80% resection (SBR). Rats were randomized to receive for 12 d either saline (S) or the enteral solution (E) through a cecostomy to meet 30% of energy requirement; the rest (70%) was provided by parenteral nutrition. Although SBR-S rats lost weight significantly compared with d 1 of the study, SBR-E rats gained. Significantly greater carcass wet weight and fat were found in SBR-E and T-E rats compared with SBR-S and T-S rats. SBR-E and T-E rats had significantly greater colonic mucosal dry weight and protein compared with SBR-S and T-S rats. Cecal short-chain fatty acid (SCFA) contents were also significantly higher in SBR-E and T-E rats compared with SBR-S and T-S rats. There was no significant effect of surgery (T vs. SBR) on any of the variables studied. These results suggest that the products of fermentation of an enteral solution infused through a cecostomy contribute substantially to energy requirement, maintenance of body composition and nutritional status of rats.

Colonic fermentation and nutritional recovery in rats with massive small bowel resection.

BACKGROUND/AIMS: After massive small bowel resection, malabsorbed carbohydrates reach the colon and undergo fermentation. This study investigates the role of colonic fermentation in rats with 80% small bowel resection on weight gain, nitrogen balance, body composition, and intestinal adaptation. METHODS: Resected or transected rats were fed a liquid diet enterally for 16 days with or without 30 mg/kg metronidazole to reduce fermentation. Weight gain was monitored until the rats were killed. Carcass composition, short-chain fatty acids in cecal content, total nitrogen output, and intestinal mucosal dry weight, protein, and DNA were measured. RESULTS: Resected rats without metronidazole had a significantly better weight gain, carcass protein, nitrogen balance, and mucosal dry weight, protein, and DNA compared with that of resected rats receiving metronidazole. There were no significant differences between the two transected groups. CONCLUSIONS: Decreasing colonic fermentation, measured by short-chain fatty acids in cecal content, reduced intestinal adaptation and nutritional recovery in rats with massive small bowel resection.