Compromised antioxidant status and persistent oxidative stress in lung transplant recipients.
Oxidative stress may be a key feature, and hence important determinant, of tissue injury and allograft rejection in lung transplant recipients. To investigate this, we determined the antioxidant status (urate, ascorbate, thiols and alpha-tocopherol) and lipid peroxidation status (malondialdehyde) in bronchoalveolar lavage (BAL) fluid and blood serum of 19 consecutive lung transplant recipients 2 weeks and 1, 2, 3, 6, and 12 months post-surgery. BAL fluid and blood samples from 23 control subjects and blood from 8 patients two days before transplantation were obtained for comparison. Before surgery, the antioxidant status of patients was poor as serum ascorbate and total thiol concentrations were significantly (p < 0.05) lower than control subjects. Two weeks post-surgery, ascorbate and total thiol concentrations were still low and urate concentrations had fallen compared to control subjects (p < 0.01). At this time, BAL fluid urate concentration was higher (p < 0.01), ascorbate concentration was lower (p < 0.01) and reduced glutathione concentrations were similar to control subjects. MDA, a product of lipid peroxidation, was higher (p < 0.01) in both BAL fluid and serum obtained from transplant patients compared to control subjects. During the first 12 months post-surgery, little improvement in antioxidant status or extent of lipid peroxidation was seen in transplant recipients. Regression analysis indicated no difference in serum or BAL fluid antioxidant status in patients with acute rejection compared to those without. In conclusion, lung transplant recipients have a compromised antioxidant status before surgery and it remains poor for at least the first year following the operation. In addition, these patients have elevated MDA concentrations in both their lung lining fluid and blood over most of this time. Oxidative stress is not, however, a sufficiently sensitive endpoint to predict tissue rejection in this group.
Williams
A
A
Cardiovascular Research, The Rayne Institute, St Thomas' Hospital, London, UK.
Riise
G C
GC
Anderson
B A
BA
Kjellström
C
C
Scherstén
H
H
Kelly
F J
FJ
D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006084:Graft Rejection / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism; D012016:Reference Values; D014527:Uric Acid / Q000378:metabolism
D000975:Antioxidants; D007166:Immunosuppressive Agents; D011506:Proteins; D014527:Uric Acid; D008315:Malondialdehyde; D016572:Cyclosporine; D005978:Glutathione; D001205:Ascorbic Acid