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Effects of phlebotomy therapy on cytochrome P450 2e1 activity and oxidative stress markers in dysmetabolic iron overload syndrome: a randomized trial

2006; Wiley; Volume: 24; Issue: 8 Linguagem: Inglês

10.1111/j.1365-2036.2006.03116.x

1365-2036

Fabrice Lainé, Jean‐Michel Reymann, François M. M. Morel, Sophie Langouët, M. Perrin, Anne Guillygomarc’h, Pierre Brissot, Valérie Turmel, Catherine Mouchel, Danielle Pape, Éric Bellissant, Yves Deugnier,

Hemoglobinopathies and Related Disorders

Summary Aim To assess the effects of iron removal on cytochrome P450 2E1 activity and oxidative stress in dysmetabolic iron overload syndrome. Methods Forty‐eight patients were randomized to phlebotomy therapy consisting of removal of 300–500 mL of blood every 14 days until serum ferritin levels dropped under 100 μ g/L or to follow‐up without phlebotomy therapy. Cytochrome P450 2E1 activity was measured at baseline and at the end of treatment by using the 6‐hydroxychlorzoxazone/chlorzoxazone blood metabolic ratio, 2 h after the intake of 500 mg of chlorzoxazone. Results In the treatment group, a mean of 3.9 ± 1.3 L of blood was removed and serum ferritin levels dropped from 715 ± 397 to 74 ± 34 μ g/L. Variation of cytochrome P450 2E1 activity was not significantly different between the 2 groups (0.07 ± 0.26 vs. 0.03 ± 0.19, P = 0.36). In the treatment group, low‐density lipoprotein cholesterol and vitamin E were lowered after treatment compared with control group (−0.15 ± 0.51 vs. 0.24 ± 0.58, P = 0.002 and −1.3 ± 4.4 vs. 2.3 ± 5.2, P = 0.03, respectively). Inversely, vitamin C was increased (0.5 ± 3.5 vs. −1.8 ± 3.9, P = 0.03). Conclusions In dysmetabolic iron overload syndrome, reduction of iron stores does not significantly influence cytochrome P450 2E1 activity but is associated with a significant decrease of low‐density lipoprotein cholesterol, suggesting that venesection therapy may be a suitable option in these patients.