Premium
High‐dose riboflavin treatment reduces the levels of BCRP‐transported cimetidine into the milk
Author(s) -
Dedina Liana,
Fujii Hisaki,
Wu Alex,
Harper Patricia,
Ito Shinya
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb557
Subject(s) - riboflavin , breast milk , cimetidine , abcg2 , mammary gland , endocrinology , chemistry , breast feeding , lactation , medicine , pharmacology , breast cancer , transporter , biology , atp binding cassette transporter , cancer , biochemistry , pregnancy , genetics , pediatrics , gene
Motherˈs milk provides a multitude of benefits to the offspring. However, drugs and toxins that are transferred into breast milk may pose a risk to the nursing infant. The Breast Cancer Resistance Protein (BCRP) is known to actively transport drugs (e.g. cimetidine) and toxins (e.g. PhIP) into breast milk. BCRP also transport nutrients such as riboflavin into breast milk and together with recently identified riboflavin transporters (RFTs), may provide a mechanism for riboflavin secretion into breast milk. It is currently not known if RFTs are expressed in the mammary gland. Our objective was to characterize BCRP and RFTs expression in the mammary gland of FVB/N mice, and to investigate a potential strategy to decrease BCRP‐transported xenobiotics excretion into the milk using a high‐dose riboflavin intervention. RFTs and BCRP expression was upregulated in the mammary gland of lactating mice. An intravenous injection of 5 μg/g body weight of riboflavin that enhanced the levels of riboflavin in milk and plasma by 3.1‐ and 8.9–fold, respectively, significantly reduced the levels of BCRP‐transported 3H‐cimetidine in milk. Also, cimetidine's milk‐to‐plasma ratio was significantly reduced (1.4 fold: p<0.05). This study demonstrates the use of riboflavin to exploit the function of mammary BCRP in order to reduce xenobiotic section into breast milk. Supported by CIHR, NSERC, Restracomp and U of T Fellowship.