title: Soy isoflavonoids exhibit in vitro biological activities of loop diuretics.
abstract: Intake of soyfoods containing isoflavonoids is related to positive effects on heart and kidney diseases. Urinary equol, a potent inhibitor of Na+-K+-2Cl- cotransport, originates from the metabolism of daidzein by intestinal bacteria. Loop diuretics (eg, furosemide), acting through inhibition of Na+-K+-2Cl- cotransport, are used to maintain adequate blood volume. In the present work, we compare isoflavonoids' inhibition of cotransport and effects on the function and hemodynamics of isolated perfused rat kidneys with those of furosemide. Equol [IC50 (half-maximal inhibitory concentration): 23.6 +/- 3.6 micromol/L], genistein (IC50: 34.8 +/- 2.6 micromol/L), and daidzein (IC50: 140.0 +/- 24 micromol/L) inhibited bumetanide-sensitive rubidium uptake in LLC-PK1 cells. The IC50 of equol and genistein was close to that of furosemide (IC50: 10.3 +/- 2.7 micromol/L). Furosemide, equol, and genistein stimulated water, sodium, and potassium excretion by isolated rat kidneys in the same temporal pattern. None of the isoflavonoids significantly increased the glomerular filtration rate, but genistein induced significant vasorelaxation. We conclude that isoflavonoids exhibit biological activities of furosemide in vitro, at concentrations similar to those reported for other in vitro effects. More research is needed to evaluate the participation of cotransport inhibition by isoflavonoids in the healthful effects claimed for soy intake.
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Medicine, University of Zaragoza, Spain.
authors.forename: R M
authors.initials: RM
authors.lastname: Martínez
authors.forename: I
authors.initials: I
authors.lastname: Giménez
authors.forename: J M
authors.initials: JM
authors.lastname: Lou
authors.forename: J A
authors.initials: JA
authors.lastname: Mayoral
authors.forename: J O
authors.initials: JO
authors.lastname: Alda
mesh_terms: D000818:Animals; D002839:Chromans / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D060754:Equol; D005665:Furosemide / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects*; D007529:Isoflavones / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D030262:Soybean Proteins / Q000494:pharmacology*
chemical_list: C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D002839:Chromans; D004232:Diuretics; D004791:Enzyme Inhibitors; D007529:Isoflavones; D008996:Monoamine Oxidase Inhibitors; D030262:Soybean Proteins; D060754:Equol; D005665:Furosemide; D019833:Genistein