Experimental and clinical data suggest that
iron has a key role in cerebral ischaemia. We measure
infarct volume and analyse the
nitric oxide responses to
brain injury in rat
stroke model after increased oral
iron intake. Permanent
middle cerebral artery occlusion (MCAO) was performed in a group of 20 male Wistar rats, 10 of which were fed with a control diet and 10 of which were fed with
iron-enriched diet containing 2.5% carbonyl
iron for 9 weeks.
L-arginine and
nitric oxide metabolites were determined in blood samples before and at 2, 6, 8 and 48 h after MCAO.
Infarct volume,
thiobarbituric acid reaction substances (
TBARS) and tissue
iron were measured at 48 h.
Infarct volume was 66% greater in the
iron-fed rats than in the control group.
Iron-fed animals showed significantly higher levels of
TBARS. Liver
iron stores (3500 +/- 199 vs 352 +/- 28 microg Fe/g, p<0.0001) but not brain
iron stores (131 +/- 11 vs 139 +/- 8 microg Fe/g, p=0.617), were significantly higher in the
iron-fed group.
L-arginine levels were slightly lower in
iron-fed rats and decreased significantly in both groups at 6 and 8 hours after MCAO. The levels of the stable end products of NOS (NOx =
nitrite +
nitrate) were significantly higher in
iron-fed rats before MCAO (16.2 +/- 2.2 vs. 9.6 +/- 0.8 micromol x L(-1), p<0.05), with a further increase during the six first hours after MCAO in both groups. These results suggest that the
iron overload that increases both
superoxide and
nitric oxide production leads to
peroxynitrite formation, thus enhancing brain damage.