Journal
JOURNAL OF BIOMEDICAL SCIENCE
Volume 13, Issue 1, Pages 127-141Publisher
BMC
DOI: 10.1007/s11373-005-9031-0
Keywords
cerebral ischemic-reperfusion; COX-2; ICAM-1 (CD54); iNOS; Mac-1 (CD11b/CD18); nuclear factor kappa B (NF-kappa B); reactive oxygen species; taxifolin
Categories
Ask authors/readers for more resources
Infarction in adult rat brain was induced by middle cerebral arterial occlusion (MCAO) followed by reperfusion to examine whether taxifolin could reduce cerebral ischemic reperfusion (CI/R) injury. Taxifolin administration (0.1 and 1.0 mu g/kg, i.v.) 60 min after MCAO ameliorated infarction (by 42%+/- 7% and 62%+/- 6%, respectively), which was accompanied by a dramatic reduction in malondialdehyde and nitrotyrosine adduct formation, two markers for oxidative tissue damage. Overproduction of reactive oxygen species (ROS) and nitric oxide (NO) via oxidative enzymes (e.g., COX-2 and iNOS) was responsible for this oxidative damage. Taxifolin inhibited leukocyte infiltration, and COX-2 and iNOS expressions in CI/R-injured brain. Taxifolin also prevented Mac-1 and ICAM-1 expression, two key counter-receptors involved in firm adhesion/transmigration of leukocytes to the endothelium, which partially accounted for the limited leukocyte infiltration. ROS, generated by leukocytes and microglial cells, activated nuclear factor-kappa B (NF-kappa B) that in turn signaled up-regulation of inflammatory proteins. NF-kappa B activity in CI/R was enhanced 2.5-fold over that of sham group and was inhibited by taxifolin. Production of both ROS and NO by leukocytes and microglial cells was significantly antagonized by taxifolin. These data suggest that amelioration of CI/R injury by taxifolin may be attributed to its anti-oxidative effect, which in turn modulates NF-kappa B activation that mediates CI/R injury.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available