Stimulation of Murine Intestinal Secretion by Daily Genistein Injections: Gender-dependent Differences

• Published in: Cellular physiology and biochemistry Vol. 28; no. 2; pp. 239 - 250
• Main Authors: Al-Nakkash, Layla, Batia, Lyn, Bhakta, Minoti, Peterson, Amity, Hale, Nathan, Skinner, Ryan, Sears, Steven, Jensen, Jesse
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01-01-2011
• Subjects: Animals; Anticarcinogenic Agents - administration & dosage; Anticarcinogenic Agents - blood; Anticarcinogenic Agents - pharmacology; Chlorides - metabolism; Colforsin - pharmacology; Cystic Fibrosis Transmembrane Conductance Regulator - antagonists & inhibitors; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Female; Genistein - administration & dosage; Genistein - blood; Genistein - pharmacology; Glyburide - pharmacology; Intestine, Small - drug effects; Intestine, Small - metabolism; Intestine, Small - pathology; Male; Mice; Mice, Inbred C57BL; Original Paper; Sex Factors; Intestine; Secretion; Genistein; CFTR
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000331736

Background/Aims: The effect of daily injections with genistein (naturally occurring phytoestrogen) on intestinal chloride (Cl - ) secretion was measured with Ussing chamber short circuit current (I sc , µA/cm 2 ), in C57BL/6J male and female mice, using 600 mg/kg genistein/day (600G), 300 mg/kg genistein/day (300G), 150 mg/kg genistein/day (150G) or genistein-free vehicle control (0G) for 1- or 2-weeks. Methods and Results: Injecting with 600G elicited significant increases in basal I sc in females after 1-week (ñ70 µA/cm 2 , n=15, p < 0.05) and in males after 2-weeks (ñ80 µA/cm 2 , n=5, p < 0.05) compared to their 0G counterparts. Chloride-free ringer significantly reduced basal I sc by 65% in 600G males and 72% in 600G females, suggesting that Cl - was the major anion comprising the genistein-stimulated secretion. The forskolin-stimulated (10 µM) I sc was significantly inhibited by the CFTR chloride channel inhibitors, glibenclamide (500 µM) and CFTR inh -172 (100 µM) in 600G males and females, suggesting some contribution by genistein-dependent CFTR-mediated Cl - secretion. We found no associated changes in intestinal morphology, nor change in total CFTR protein with 600G. There was a 5% increase in apical/subapical ratio in 600G males compared to controls (no change in females). Conclusion: These data suggest that male and female mice both exhibit increased Cl- secretion with 600G, however, the mechanisms mediating this are gender-dependent.