Ubiquity of Synthetic Phenolic Antioxidants in Children's Cerebrospinal Fluid from South China: First Evidence for Their Penetration across the Blood-Cerebrospinal Fluid Barrier.

Synthetic phenolic antioxidants (SPAs) and relevant transformation products (TPs) are potentially neurotoxic pollutants to which humans are widely exposed. However, their penetration behavior across the brain barrier and associated exposure to the central nervous system (CNS) remain unknown. This study is the first to investigate a wide range of 30 SPAs and TPs, including emerging SPAs, in matched serum and cerebrospinal fluid (CSF) samples from children in Guangzhou, China. Sixty-two children of either sex aged <14 years with nonbloody CSF and complete clinical information were included. The findings demonstrated the ubiquitous occurrence of many SPAs and TPs, particularly BHT, 2,4-di-tert-butylphenol (DBP), AO 1010, AO 1076, BHT-Q, and BHT-quinol, not only in serum but also in the CSF. Median total concentrations of SPAs and TPs were up to 22.0 and 2.63 ng/mL in serum and 14.5 and 2.11 ng/mL in CSF, respectively. On calculating the penetration efficiencies across the blood-CSF barrier (BCSFB) (RCSF/serum, CCSF/Cserum) for selected SPAs and TPs, their RCSF/serum values (median 0.52-1.41) were highly related to their physicochemical properties, indicating that passive diffusion may be the potential mechanism of BCSFB penetration. In addition, the RCSF/serum values were positively correlated with the barrier permeability index RAlb (AlbuminCSF/Albuminserum), indicating that barrier integrity is an important determinant of BCSFB penetration. Overall, these results will improve our perception of human internal exposure to SPAs and lay a solid foundation for assessing the risk of CNS exposure to various SPAs.

Identification and quantification of (poly)phenol and methylxanthine metabolites in human cerebrospinal fluid: evidence of their ability to cross the BBB.

Increasing evidence suggests that dietary (poly)phenols and methylxanthines have neuroprotective effects; however, little is known about whether they can cross the blood-brain barrier (BBB) and exert direct effects on the brain. We investigated the presence of (poly)phenol and methylxanthine metabolites in plasma and cerebrospinal fluid (CSF) from 90 individuals at risk of dementia using liquid chromatography-mass spectrometry and predicted their mechanism of transport across the BBB using in silico modelling techniques. A total of 123 and 127 metabolites were detected in CSF and plasma, respectively. In silico analysis suggests that 5 of the 20 metabolites quantified in CSF can cross the BBB by passive diffusion, while at least 9 metabolites require the aid of cell transporters to cross the BBB. Our results showed that (poly)phenols and methylxanthines are bioavailable, can cross the BBB via passive diffusion or transport carriers, and can reach brain tissues to exert neuroprotective effects.

Quantification of phenolic antioxidants in rat cerebrospinal fluid by GC-MS after oral administration of compounds.

A gas chromatographic-mass spectrometric (GC-MS) method for qualitative and subsequent quantitative analysis of phenolic antioxidants compounds, presents in olive oil, in rat cerebrospinal fluid (CSF) after oral administration of compounds is proposed. The procedure involves the extraction of compounds from the samples by a traditional microliquid-liquid extraction method, followed by a silylation step before the GC-MS analysis. The chromatographic separation was performed by using a low bleed DB5-MS fused-silica capillary column. The presence of 21 phenolic compounds was tested in CSF extracts and only free tyrosol, hydroxytyrosol and ferulic acid were detected. Those compounds were then quantitatively determined using the proposed methology. The molecular ion for silylated compounds appears at 370 m/z for hydroxytyrosol, 282 m/z for tyrosol and 338 m/z for ferulic acid respectively, while the base peak appears at 267 m/z, 179 m/z and 338 m/z. alpha-Naphthol was used as a surrogate (216 and 201 m/z). The detection capabilities obtained were 74, 92 and 79 ng/mL respectively. The method was applied to the determination of trace amounts of compounds in rat cerebrospinal fluid after oral administration. The animals were fed with a standard chow diet (free of phenolic antioxidants) in order to avoid the influence of any other component of the diet on the CSF of the animals.