Sex Differences in the Absorption, Disposition, Metabolism, and Excretion of Grape Seed Proanthocyanidins in Prepubescent Rats.

Scope: The absorption, disposition, metabolism, and excretion (ADME) of phenolic compounds are key factors in determining their bioactivity. The group demonstrates that the ADME of a Grape Seed Proanthocyanidin Extract (GSPE) depends on sex in adult rats and specifically, methylated metabolites are only quantified in brain male adult rats. The aim of this study is to determine whether these differences exist before puberty.

Methods And Results: Prepubescent 4-week-old male and female Wistar rats are administered GSPE at a dose of 1000 mg kg. Plasma, liver, mesenteric white adipose tissue (MWAT), brain, and kidneys are extracted excised 2 h after GSPE administration, and the PAs metabolite profile is studied by HPLC-ESI-MS/MS. Moreover, plasma estradiol and brain and liver catechol-O-methyltransferase (COMT) protein levels are also studied. Results showed that there are no differences in plasma and brain among sexes and only differences are observed in liver, MWAT, and kidney with individual metabolites. This agrees with the lack of differences in estradiol and COMT levels among sexes. However, the ADME of PAs metabolites is higher in male rats.

Conclusions: The results demonstrate lack of sex-dependence in metabolite profile in prepubescent rats, suggesting that sex differences in the metabolism of GSPE occur due to puberty.