Cytochrome P450 1A1 (CYP1A1) T6325C polymorphism might modulate essential hypertension-associated stroke risk.

Stroke is a serious complication associated with hypertension. Because cytochrome P450 1A1 (CYP1A1) is involved in the production of arachidonic acid-derived vasoactive substances, we hypothesized that CYP1A1 functional polymorphisms (linked to changes in enzyme activity) might be related to pathological conditions associated with essential hypertension. We genotyped 32 patients with hypertension for three CYP1A1 polymorphisms, and individuals with or without history of previous stroke were compared. These results were also compared with a control population sample of 152. The distributions of T6235C (m1) CYP1A1 genotypes in patients with (TT: 44.4%; TC/CC: 55.6%; n = 9) and without stroke (TT: 82.6%; TC/CC: 17.4%; n = 23) indicate that the C allele is associated with stroke (OR = 5.94; 95% C = 1.46 - 24.23). No association was found between the polymorphism studied and essential hypertension. Our results suggest a relationship between CYP1A1 activity and incidence of stroke in patients with essential hypertension, but no conclusion can be drawn regarding an association with essential hypertension.

Flavonoids and urate antioxidant interplay in plasma oxidative stress.

Flavonoids are naturally occurring plant compounds with antioxidant properties. Their consumption has been associated with the protective effects of certain diets against some of the complications of atherosclerosis. Low-density lipoprotein (LDL) oxidative modification is currently thought to be a significant event in the atherogenic process. Most of the experiments concerning the inhibition of LDL oxidation used isolated LDL. We used diluted human whole plasma to study the influence of flavonoids on lipid peroxidation (LPO) promoted by copper, and their interaction with uric acid, one of the most important plasma antioxidants. Lipid peroxidation was evaluated by the formation of thiobarbituric acid reactive substances (TBARS) and of free malondialdehyde (MDA). The comparative capability of the assayed flavonoids on copper (II) reduction was tested using the neocuproine colorimetric test. In our assay system, urate disappears and free MDA and TBARS formation increase during the incubation of plasma with copper. Most of the tested flavonoids inhibited copper-induced LPO. The inhibition of LPO by flavonoids correlated positively with their capability to reduce copper (II). The urate consumption during the incubation of plasma with copper was inhibited by myricetin, quercetin and kaempferol. The inhibition of urate degradation by flavonoids correlated positively with the inhibition of LPO. Urate inhibited the copper-induced LPO in a concentration-dependent mode. Luteolin, rutin, catechin and quercetin had an antioxidant synergy with urate. Our results show that some flavonoids could protect endogenous urate from oxidative degradation, and demonstrate an antioxidant synergy between urate and some of the flavonoids.