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GENISTEIN DIET: EFFECTS ON JEJUNUM FROM THE R117H CYSTIC FIBROSIS MICE
Author(s) -
Polito Sarah,
Drumm Mitch L.,
Al-Nakkash Layla
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.1157.1
Subject(s) - endocrinology , medicine , basal (medicine) , forskolin , chemistry , stimulation , insulin
We have previously shown wild‐type (Wt) C57BL/6J mice fed a genistein‐containing diet (600 mg/kg food, 600G) for 1‐month, have significantly elevated basal levels of jejunal chloride (Cl) secretion (measured as transepithelial short circuit current, Isc) compared to mice fed a genistein‐free diet (0G); a gender‐specific response to 600G, i.e. females produced a significant increase in Cl secretion, whereas no response was observed in males. We fed male and female cystic fibrosis R117H mutant mice, 600G and 0G diets for 1‐month. Basal Isc was unchanged in 600G male mice (40.4 ± 15.2 μA/cm 2 , n = 7) compared to 0G controls (34.9 ± 7.7 μA/cm 2 , n = 9). Basal Isc was significantly increased in 600G female mice (39.1 ± 7.4 μA/cm 2 , n = 3) compared to 0G controls (24.8 ± 3.0 μA/cm 2 , n = 3). Comparable steady‐state increases in Isc in response to forskolin (10 μm, bilateral) were observed in 600G and 0G male and female mice. There was no effect of the inhibitor of the Na + /K + /2Cl − co‐transporter, bumetanide (100 μm, basolateral), on the forskolin‐stimulated Isc in either 600G or 0G fed male and female mice. Addition of acetazolamide (100 μm, bilateral) to block the HCO 3 − secretory component, produced an increase in the percentage inhibition in 600G fed males (11.9 ± 3.0 %, n = 7) and 600G fed females (13.7 ± 1.9 %, n = 3), compared to their respective controls. In the male R117H mice there were no changes in jejunal morphology associated with the diet groups (villi length, number of goblet cells per villi, crypt depth and number of goblet cells per crypt). These data suggest that, in male R117H mice, a 4‐week diet treatment with 600G does not provide any benefits towards the overall magnitude of basal or forskolin‐mediated secretion, but in female R117H mice there is improvement in basal Isc with the 600G diet. Sarah Polito was supported by the Midwestern University Summer DO Fellowship Program. Layla Al‐Nakkash was supported by the Soy Health Research Fund.