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Effect of genistein on basal jejunal chloride secretion in R117H CF mice is sex and route specific.

Rayyan E, Polito S, Leung L, Bhakta A, Kang J, Willey J, Mansour W, Drumm ML, Al-Nakkash L - Clin Exp Gastroenterol (2015)

Bottom Line: Genistein, a naturally occurring phytoestrogen, is known to stimulate CFTR function in vitro.Isc was measured in response to the following: the adenylate cyclase activator forskolin (10 μM, bilateral), bumetanide (100 μM, basolateral) to indicate the Cl(-) secretory component, and acetazolamide (100 μM, bilateral) to indicate the HCO3 (-) secretory component; however, there was no effect of genistein (diet or injection) on any of these parameters.Serum levels of genistein were significantly elevated, compared to respective controls, by either 600Gd (equally elevated in males and females) or 600Gi (elevated more in females versus males).

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA.

ABSTRACT
Cystic fibrosis (CF) results from the loss or reduction in function of the CFTR (cystic fibrosis transmembrane conductance regulatory protein) chloride channel. The third most common CFTR mutation seen clinically is R117H. Genistein, a naturally occurring phytoestrogen, is known to stimulate CFTR function in vitro. We aimed to determine whether route of administration of genistein could mediate differential effects in R117H male and female CF mice. Mice were fed (4 weeks) or injected subcutaneously (1 week) with the following: genistein 600 mg/kg diet (600Gd); genistein-free diet (0Gd); genistein injection 600 mg/kg body weight (600Gi); dimethyl sulfoxide control (0Gi). In male R117H mice fed 600Gd, basal short circuit current (Isc) was unchanged. In 600Gd-fed female mice, there was a subgroup that demonstrated a significant increase in basal Isc (53.14±7.92 μA/cm(2), n=6, P<0.05) and a subgroup of nonresponders (12.05±6.59 μA/cm(2), n=4), compared to 0Gd controls (29.3±6.5 μA/cm(2), n=7). In R117H mice injected with 600Gi, basal Isc was unchanged in both male and female mice compared to 0Gi controls. Isc was measured in response to the following: the adenylate cyclase activator forskolin (10 μM, bilateral), bumetanide (100 μM, basolateral) to indicate the Cl(-) secretory component, and acetazolamide (100 μM, bilateral) to indicate the HCO3 (-) secretory component; however, there was no effect of genistein (diet or injection) on any of these parameters. Jejunal morphology (ie, villi length, number of goblet cells per villus, crypt depth, and number of goblet cells per crypt) in R117H mice suggested no genistein-mediated difference among the groups. Serum levels of genistein were significantly elevated, compared to respective controls, by either 600Gd (equally elevated in males and females) or 600Gi (elevated more in females versus males). These data suggest a sex-dependent increase in basal Isc of R117H mice and that the increase is also specific for route of administration.

No MeSH data available.


Related in: MedlinePlus

Representative sections from R117H jejunum stained with hematoxylin and eosin.Notes: (A) Typical section from a 0Gd-administered male R117H mouse jejunum. (B) Typical section from a 600Gd-administered male R117H mouse jejunum. Images taken at ×10 magnification.Abbreviations: 600Gd, 600 mg genistein/kg diet; 0Gd, genistein-free diet.
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f6-ceg-8-077: Representative sections from R117H jejunum stained with hematoxylin and eosin.Notes: (A) Typical section from a 0Gd-administered male R117H mouse jejunum. (B) Typical section from a 600Gd-administered male R117H mouse jejunum. Images taken at ×10 magnification.Abbreviations: 600Gd, 600 mg genistein/kg diet; 0Gd, genistein-free diet.

Mentions: To determine whether there were genistein-mediated or sex-dependent effects on intestinal morphology, histological sections of jejunum were stained using hematoxylin and eosin and analyzed for wall thickness, villi length, crypt depth, and numbers of goblet cells within entire villi and crypts using Axiovision software. Data are shown in Table 2, and representative hematoxylin-and-eosin-stained histological images are shown in Figure 6. Number of goblet cells per villus was significantly greater in the female 0Gd group compared to their male counterparts (P<0.05), which may indicate a greater mucus production in R117H females versus males, that were fed the casein-based genistein-free diet. There were no other effects of sex or genistein (regardless of route of administration) on the parameters measured.


Effect of genistein on basal jejunal chloride secretion in R117H CF mice is sex and route specific.

Rayyan E, Polito S, Leung L, Bhakta A, Kang J, Willey J, Mansour W, Drumm ML, Al-Nakkash L - Clin Exp Gastroenterol (2015)

Representative sections from R117H jejunum stained with hematoxylin and eosin.Notes: (A) Typical section from a 0Gd-administered male R117H mouse jejunum. (B) Typical section from a 600Gd-administered male R117H mouse jejunum. Images taken at ×10 magnification.Abbreviations: 600Gd, 600 mg genistein/kg diet; 0Gd, genistein-free diet.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321419&req=5

f6-ceg-8-077: Representative sections from R117H jejunum stained with hematoxylin and eosin.Notes: (A) Typical section from a 0Gd-administered male R117H mouse jejunum. (B) Typical section from a 600Gd-administered male R117H mouse jejunum. Images taken at ×10 magnification.Abbreviations: 600Gd, 600 mg genistein/kg diet; 0Gd, genistein-free diet.
Mentions: To determine whether there were genistein-mediated or sex-dependent effects on intestinal morphology, histological sections of jejunum were stained using hematoxylin and eosin and analyzed for wall thickness, villi length, crypt depth, and numbers of goblet cells within entire villi and crypts using Axiovision software. Data are shown in Table 2, and representative hematoxylin-and-eosin-stained histological images are shown in Figure 6. Number of goblet cells per villus was significantly greater in the female 0Gd group compared to their male counterparts (P<0.05), which may indicate a greater mucus production in R117H females versus males, that were fed the casein-based genistein-free diet. There were no other effects of sex or genistein (regardless of route of administration) on the parameters measured.

Bottom Line: Genistein, a naturally occurring phytoestrogen, is known to stimulate CFTR function in vitro.Isc was measured in response to the following: the adenylate cyclase activator forskolin (10 μM, bilateral), bumetanide (100 μM, basolateral) to indicate the Cl(-) secretory component, and acetazolamide (100 μM, bilateral) to indicate the HCO3 (-) secretory component; however, there was no effect of genistein (diet or injection) on any of these parameters.Serum levels of genistein were significantly elevated, compared to respective controls, by either 600Gd (equally elevated in males and females) or 600Gi (elevated more in females versus males).

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA.

ABSTRACT
Cystic fibrosis (CF) results from the loss or reduction in function of the CFTR (cystic fibrosis transmembrane conductance regulatory protein) chloride channel. The third most common CFTR mutation seen clinically is R117H. Genistein, a naturally occurring phytoestrogen, is known to stimulate CFTR function in vitro. We aimed to determine whether route of administration of genistein could mediate differential effects in R117H male and female CF mice. Mice were fed (4 weeks) or injected subcutaneously (1 week) with the following: genistein 600 mg/kg diet (600Gd); genistein-free diet (0Gd); genistein injection 600 mg/kg body weight (600Gi); dimethyl sulfoxide control (0Gi). In male R117H mice fed 600Gd, basal short circuit current (Isc) was unchanged. In 600Gd-fed female mice, there was a subgroup that demonstrated a significant increase in basal Isc (53.14±7.92 μA/cm(2), n=6, P<0.05) and a subgroup of nonresponders (12.05±6.59 μA/cm(2), n=4), compared to 0Gd controls (29.3±6.5 μA/cm(2), n=7). In R117H mice injected with 600Gi, basal Isc was unchanged in both male and female mice compared to 0Gi controls. Isc was measured in response to the following: the adenylate cyclase activator forskolin (10 μM, bilateral), bumetanide (100 μM, basolateral) to indicate the Cl(-) secretory component, and acetazolamide (100 μM, bilateral) to indicate the HCO3 (-) secretory component; however, there was no effect of genistein (diet or injection) on any of these parameters. Jejunal morphology (ie, villi length, number of goblet cells per villus, crypt depth, and number of goblet cells per crypt) in R117H mice suggested no genistein-mediated difference among the groups. Serum levels of genistein were significantly elevated, compared to respective controls, by either 600Gd (equally elevated in males and females) or 600Gi (elevated more in females versus males). These data suggest a sex-dependent increase in basal Isc of R117H mice and that the increase is also specific for route of administration.

No MeSH data available.


Related in: MedlinePlus