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Effect of apoE genotype and vitamin E on biomarkers of oxidative stress in cultured neuronal cells and the brain of targeted replacement mice

100%

Huebbe P., Jofre-Monseny L., Boesch-Saadatmandi C., Minihane A. M., Rimbach G.

Journal of Physiology and Pharmacology

2007

tom 58

nr 4

The aetiology of apoE4 genotype-Alzheimer’s disease (AD) association are complex. The current study emphasizes the impact of apoE genotype and potential beneficial effects of vitamin E (VE) in relation to oxidative stress. Agonist induced neuronal cell death was examined 1) in the presence of conditioned media containing equal amounts of apoE3 or apoE4 obtained from stably transfected macrophages, and 2) after pretreatment with alpha- and -tocopherol, and -tocotrienol. ApoE3 and apoE4 transgenic mice were fed a diet poor or rich in VE to study the interplay of both apoE genotype and VE status, on membrane lipid peroxidation, antioxidative enzyme activity and glutathione levels in the brain. Cytotoxicity of hydrogen peroxide and glutamate was higher in neuronal cells cultured with apoE4 than apoE3 conditioned media. VE pre-treatment of neurons counteracted the cytotoxicity of a peroxide challenge but not of nitric oxide. No significant effects of apoE genotype or VE supplementation were observed on lipid peroxidation or antioxidative status in the brain of apoE3 and apoE4 mice. VE protects against oxidative insults in vitro, however, no differences in brain oxidative status were observed in mice. Unlike in cultured cells, apoE4 may not contribute to higher neuronal oxidative stress in the brain of young targeted replacement mice.

Effect of quercetin on paraoxonase 1 activity - studies in cultured cells, mice and humans

72%

Boesch-Saadatmandi C., Egert S., Schrader C., Coumoul X., Barouki R., Muller M. J., Wolffram S., Rimbach G.

Journal of Physiology and Pharmacology

2010

tom 61

nr 1

99-105

There is increasing evidence that the HDL-associated enzyme paraoxonase 1 (PON1) may have a protective function in the atherosclerotic process. An enhancement of PON1 activity by dietary factors including flavonoids is therefore of interest. Quercetin, a flavonol frequently present in fruits and vegetables has been shown to induce PON1 in cultured liver cells, but the in vivo efficacy of a dietary quercetin supplementation has yet not been evaluated. To this end, we fed laboratory mice quercetin-enriched diets with quercetin concentrations ranging from 0.05 to 2 mg/g diet for 6 weeks and determined the expression of the hepatic PON1 gene and its protein levels. Since we could establish a moderate but significant induction of PON1 mRNA levels by dietary quercetin in mice, we aimed to proof whether healthy human volunteers, given graded supplementary quercetin (50, 100 or 150 mg/day) for two weeks, would respond with likewise enhanced plasma paraoxonase activities. However, PON1 activity towards phenylacetate and paraoxon was not changed following quercetin supplementation in humans. Differences between mice and humans regarding the PON1 inducing activity of quercetin may be related to differences in quercetin metabolism. In mice, unlike in humans, a large proportion of quercetin is methylated to isorhamnetin which exhibits, according to our reporter gene data in cultured liver cells, a potent PON1 inducing activity.

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

2 Boesch-Saadatmandi C.

2 Rimbach G.

1 Barouki R.

1 Coumoul X.

1 Egert S.

1 Huebbe P.

1 Jofre-Monseny L.

1 Minihane A. M.

1 Muller M. J.

1 Schrader C.

1 Wolffram S.

1 2010

1 2007

Wyniki wyszukiwania

Effect of apoE genotype and vitamin E on biomarkers of oxidative stress in cultured neuronal cells and the brain of targeted replacement mice

Effect of quercetin on paraoxonase 1 activity - studies in cultured cells, mice and humans