TY - JOUR
T1 - Sex-specific pharmacokinetic response to phytoestrogens in Drosophila melanogaster
AU - Sadova, Nadiia
AU - Blank-Landeshammer, Bernhard
AU - Curic, David
AU - Iken, Marcus
AU - Weghuber, Julian
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/6/1
Y1 - 2024/6/1
N2 - Drosophila melanogaster, or the fruit fly, is widely used for modeling numerous human diseases, such as neurodegeneration, tumor development, cachexia, and intestinal dysfunction. It is a suitable model organism for research targeting the physiology and pathophysiology of the intestinal epithelial barrier and has also been used as a model organism for preliminary drug and bioactive nutrient screening. However, the application of D. melanogaster in research on drug bioavailability and pharmacokinetic properties has not yet been well explored. In this study, we applied D. melanogaster to investigate the absorption and excretion of the orally administered phytoestrogens daidzein, glycitein, genistein, and their glycosides. Therefore, we established a quick, noninvasive method to quantify compound retention in D. melanogaster, suitable for the investigation of a broad variety of potentially bioactive substances. We showed that fruit fly sex plays a key role in the metabolization, transportation, and excretion of phytoestrogenic isoflavones. In particular, female fruit flies retained significantly more isoflavones than male fruit flies, which was reflected in the greater metabolic impact of isoflavones on females. Male fruit flies excreted more isoflavones than females did, which was linked to the upregulation of the xenobiotic transporter gene Mdr50. We also demonstrated that micellized isoflavones were more bioavailable than powdered isoflavones, independent of sex, age or the addition of dietary fibers.
AB - Drosophila melanogaster, or the fruit fly, is widely used for modeling numerous human diseases, such as neurodegeneration, tumor development, cachexia, and intestinal dysfunction. It is a suitable model organism for research targeting the physiology and pathophysiology of the intestinal epithelial barrier and has also been used as a model organism for preliminary drug and bioactive nutrient screening. However, the application of D. melanogaster in research on drug bioavailability and pharmacokinetic properties has not yet been well explored. In this study, we applied D. melanogaster to investigate the absorption and excretion of the orally administered phytoestrogens daidzein, glycitein, genistein, and their glycosides. Therefore, we established a quick, noninvasive method to quantify compound retention in D. melanogaster, suitable for the investigation of a broad variety of potentially bioactive substances. We showed that fruit fly sex plays a key role in the metabolization, transportation, and excretion of phytoestrogenic isoflavones. In particular, female fruit flies retained significantly more isoflavones than male fruit flies, which was reflected in the greater metabolic impact of isoflavones on females. Male fruit flies excreted more isoflavones than females did, which was linked to the upregulation of the xenobiotic transporter gene Mdr50. We also demonstrated that micellized isoflavones were more bioavailable than powdered isoflavones, independent of sex, age or the addition of dietary fibers.
KW - compound absorption
KW - compound excretion
KW - Drosophila melanogaster
KW - isoflavone
KW - phytoestrogen
KW - phytogenic drugs
UR - http://www.scopus.com/inward/record.url?scp=85191009566&partnerID=8YFLogxK
U2 - 10.1016/j.biopha.2024.116612
DO - 10.1016/j.biopha.2024.116612
M3 - Article
SN - 0753-3322
VL - 175
SP - 116612
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 116612
ER -