Quercetin is a dietary polyphenolic compound with potentially beneficial effects on health. Claims that quercetin has biological effects are based mainly on in vitro studies with quercetin aglycone. However, quercetin is rapidly metabolized, and we have little knowledge of its availability to tissues. To assess the long-term tissue distribution of quercetin, 2 groups of rats were given a 0.1 or 1% quercetin diet [approximately 50 or 500 mg/kg body weight (wt)] for 11 wk. In addition, a 3-d study was done with pigs fed a diet containing 500 mg quercetin/kg body wt. Tissue concentrations of quercetin and quercetin metabolites were analyzed with an optimized extraction method. Quercetin and quercetin metabolites were widely distributed in rat tissues, with the highest concentrations in lungs (3.98 and 15.3 nmol/g tissue for the 0.1 and 1% quercetin diet, respectively) and the lowest in brain, white fat, and spleen. In the short-term pig study, liver (5.87 nmol/g tissue) and kidney (2.51 nmol/g tissue) contained high concentrations of quercetin and quercetin metabolites, whereas brain, heart, and spleen had low concentrations. These studies have for the first time identified target tissues of quercetin, which may help to understand its mechanisms of action in vivo.

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BackgroundSurface charge and oxidative stress are often hypothesized to be important factors in cytotoxicity of nanoparticles. However, the role of these factors is not well understood. Hence, the aim of this study was to systematically investigate the role of surface charge, oxidative stress and possible involvement of mitochondria in the production of intracellular reactive oxygen species (ROS) upon exposure of rat macrophage NR8383 cells to silicon nanoparticles. For this aim highly monodisperse (size 1.6 ± 0.2 nm) and well-characterized Si core nanoparticles (Si NP) were used with a surface charge that depends on the specific covalently bound organic monolayers: positively charged Si NP-NH2, neutral Si NP-N3 and negatively charged Si NP-COOH.ResultsPositively charged Si NP-NH2 proved to be more cytotoxic in terms of reducing mitochondrial metabolic activity and effects on phagocytosis than neutral Si NP-N3, while negatively charged Si NP-COOH showed very little or no cytotoxicity. Si NP-NH2 produced the highest level of intracellular ROS, followed by Si NP-N3 and Si NP-COOH; the latter did not induce any intracellular ROS production. A similar trend in ROS production was observed in incubations with an isolated mitochondrial fraction from rat liver tissue in the presence of Si NP. Finally, vitamin E and vitamin C induced protection against the cytotoxicity of the Si NP-NH2 and Si NP-N3, corroborating the role of oxidative stress in the mechanism underlying the cytotoxicity of these Si NP.ConclusionSurface charge of Si-core nanoparticles plays an important role in determining their cytotoxicity. Production of intracellular ROS, with probable involvement of mitochondria, is an important mechanism for this cytotoxicity.

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