Effects of phlebotomy therapy on cytochrome P450 2e1 activity and oxidative stress markers in dysmetabolic iron overload syndrome: a randomized trial.
OBJECTIVE
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 microg/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 microg/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.
Lainé
F
F
Centre d'Investigation Clinique INSERM 0203, CHU Pontchaillou, 35033 Rennes, France. fabrice.laine@chu-rennes.fr
Reymann
J M
JM
Morel
F
F
Langouët
S
S
Perrin
M
M
Guillygomarc'h
A
A
Brissot
P
P
Turmel
V
V
Mouchel
C
C
Pape
D
D
Bellissant
E
E
Deugnier
Y
Y
D001205:Ascorbic Acid / Q000097:blood; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D005293:Ferritins / Q000097:blood; D006801:Humans; D019190:Iron Overload / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress / Q000502:physiology*; D018962:Phlebotomy / Q000379:methods*; D011446:Prospective Studies; D014810:Vitamin E / Q000097:blood
D015415:Biomarkers; D008078:Cholesterol, LDL; D014810:Vitamin E; D008315:Malondialdehyde; D005293:Ferritins; D019392:Cytochrome P-450 CYP2E1; D001205:Ascorbic Acid