PubMed Health⌕ Search

Biomedical subjects

S Hendrich

Publications and source records attributed to S Hendrich.

At least 19 recordsLinked to original sources

Reaction of fumonisin with glucose prevents promotion of hepatocarcinogenesis in female F344/N rats while maintaining normal hepatic sphinganine/sphingosine ratios.

The reaction of the primary amine of fumonisin B(1) (FB(1)) with glucose was hypothesized to detoxify this mycotoxin. Eighty 10-day-old female F344/N rats were injected intraperitoneally with diethylnitrosamine (DEN; 15 mg/kg of body weight). At 4 weeks of age, the weaned rats were randomly assigned to one of four treatment groups with 20 rats each. At 9 weeks of age, four rats from each treatment group were killed. At 12 weeks, another five rats from each group were killed. At 20 weeks of age, the remaining rats were killed. In comparison with the rats fed basal diet or FB(1)-glucose (containing 25 ppm of FB(1)), rats fed 8 ppm (residual amount of free FB(1) in the FB(1)-glucose mixture) or 25 ppm of FB(1) had greater alanine aminotransferase activity at 9 and 20 weeks of age (P < 0.001), greater endogenous hepatic prostaglandin E(2) production at 20 weeks of age (P < 0.05), and significantly lower plasma cholesterol at 20 weeks of age (P < 0.01). Placental glutathione S-transferase (PGST)-positive and gamma-glutamyltransferase (GGT)-positive altered hepatic foci (AHF) occurred only in rats fed 25 ppm of FB(1) at 20 weeks of age. Hepatic natural killer (NK) cell activities were similar among the four groups, but the percentage of total liver-associated mononuclear cells exhibiting the NKR-P1(bright) marker was significantly greater in rats fed FB(1)-glucose, FB(1) (8 ppm) and FB(1) (25 ppm) than in control rats at 9 weeks of age, and FB(1)-glucose-treated rats had significantly lower NKR-P1(bright) cells as a percentage of total liver-associated mononuclear cells than rats fed 25 ppm of FB(1) at 20 weeks of age (P < 0.05). PGST- or GGT-positive AHF were not detected in any treatment group at 9 or 12 weeks of age. At 20 weeks of age, half of the rats fed 25 ppm of FB(1) had PGST- and GGT-positive AHF. The sphinganine (Sa) concentration and the Sa/sphingosine (So) ratio were significantly greater in the rats fed 25 ppm of FB(1) diet as compared with the control groups at, respectively, 12 or 20 weeks of age. Therefore, modifying FB(1) with glucose seems to prevent FB(1)-induced hepatotoxicity and promotion of hepatocarcinogenesis. The Sa/So ratio was not the most sensitive biomarker of FB(1) toxicity.

Alkylating Agents↗

Effects of soy foods on ovarian function in premenopausal women.

It has been proposed that the high intake of soy foods among Asians may partly explain their lower rates of breast cancer, perhaps by lowering endogenous oestrogen levels, although this has been inadequately studied. Twenty healthy cycling premenopausal women (ten Asians and ten non-Asians) participated in a 7-month soy intervention study which was designed to investigate the effect of supplementation on ovarian function. Asian soy foods (tofu, soymilk, green soybean peas) in the amount of approximately 32 mg of isoflavones per day were added to the women's diets for three menstrual cycles. The women's baseline (two cycles) serum hormone levels were compared to levels during soy intervention (three cycles) and levels after intervention (two cycles). During the entire study period, subjects provided almost daily overnight urine samples and blood specimens during specified days of their menstrual cycles. The day of urinary luteinizing hormone (LH) peak was used as a marker for the day of ovulation. Knowledge of day of ovulation allowed comparison of hormone measurements at baseline to those obtained during intervention and recovery cycles with standardization of day of cycle. Soy intervention was associated with a statistically significant reduction in serum luteal oestradiol level (-9.3%, P < 0.05), but there were no significant changes in follicular phase oestradiol, follicular or luteal phase progesterone, sex hormone-binding globulin or menstrual cycle length. This significant reduction in luteal phase oestradiol was, however, observed only among Asian (-17.4%) but not among non-Asian (-1.2%) participants; urinary excretion of isoflavones was higher among Asians than non-Asians (29.2 vs 17.1 micromol day(-1), P= 0.16) during the intervention period. Thus, supplementation using traditional soy foods reduced serum oestradiol levels among Asian participants in this study. Differences in the type of soy products (i.e. traditional soy foods versus soy protein products), amount of isoflavones, and race/ethnicity of participants may have contributed to the divergent results. Larger soy intervention studies designed specifically to include participants of different race/ethnicities and using both traditional soy foods and soy protein products providing comparable doses of isoflavones are needed to definitively determine the effect of soy on ovarian function.

Adult↗

Opposing effects of prostaglandin E(2)and F(2 alpha) on rat liver-associated natural killer cell activity in vitro.

Strain differences in cancer incidence are proposed to be due partly to differences in immune function. As potential cancer-associated immunological regulators, the concentrations of hepatic prostaglandins E(2)(PGE(2 alpha)and F(2 alpha)(PGF(2 alpha)) were compared in 9-week-old male and female F344/N and Sprague-Dawley (SD) rats. There were no strain or gender differences in the concentrations of hepatic PGE(2). No strain difference was found in the concentration of hepatic PGF(2 alpha), but the hepatic PGF(2 alpha)concentration in female rats was two-fold that of the male rat (130 vs 60 ng/g). PGE(2)significantly inhibited hepatic natural-killer cell (NK) activity in vitro compared with untreated cells from both genders and strains (P<0.05), 25 ng PGE(2)/ml inhibited NK activity significantly more than did 10 ng PGE(2)/ml (P<0.05). In contrast, 50 ng PGF(2 alpha)/ml and 100 ng PGF(2 alpha)/ml significantly stimulated hepatic NK activity compared with untreated hepatic cells from both F344/N and SD rats. This study suggests that prostaglandins may have a negligible net effect on NK activity associated with rat liver, and may be unlikely to mediate cancer-related immune function.

Analysis of Variance↗

Neither background diet nor type of soy food affects short-term isoflavone bioavailability in women.

To characterize bioavailability of soybean isoflavones, proposed anticarcinogenic food components, eight women, ages 20-41 y, were fed 0.9 mg isoflavones/kg body wt from soymilk at 0730, 1230 and 1730 h for 1 d. Subjects consumed three background diets in random order: a diet prepared for them (basic foods diet) or a self-selected diet at the specified times, or a self-selected diet eaten ad libitum. In a second study, women were fed single isoflavone doses of 0.8-1.4 mg/kg in breakfast casseroles containing tofu, tempeh, cooked soybeans or texturized vegetable protein. Both studies were conducted in randomized, cross-over designs. Plasma, urine and fecal isoflavones were measured by reverse-phase HPLC. After consumption of background diets, 48-h urinary recovery of daidzein (D) was 26-27%, and of genistein (G), 18-20% of the dose given with each diet. At 24 h after consumption of different background diets, plasma D and G concentrations were similar (1.4 +/- 0.7 mmol/L) and were not affected by diet selection. Urinary recoveries of D over 24 h from the various soy foods were 38-51%, and of G, 9-16% of the dose given. In both studies, urinary recovery of D was significantly greater than that of G. Only a few percentage of the total isoflavone dose was recovered in feces, probably due to bacterial breakdown of these compounds. Therefore, isoflavone bioavailability may not be affected by choice of background diet or food source of isoflavones.

Adult↗

Estrogenic activity of glycitein, a soy isoflavone.

Glycitein (4',7-dihydroxy-6-methoxyisoflavone) accounts for 5-10% of the total isoflavones in soy food products. The biological activity of this compound has not been reported to date, although numerous studies have been performed with the other soy isoflavones, daidzein and genistein. Glycitein was isolated from soy germ to 99% purity. Weaning female B6D2F1 mice were dosed with glycitein (3 mg/day), genistein (3 mg/day), and diethylstilbestrol (DES) (0.03 microg/day) in 5% Tween 80 by gavage for 4 days. A control group received an equal volume of 5% Tween 80 solution daily. The uterine weight increased 150% with glycitein (p < 0.001), 50% with genistein (p < 0. 001), and 60% with DES (p < 0.001) compared with the control group. DES, 17beta-estradiol, and three isoflavones (daidzein, genistein, and glycitein) were examined for their competitive binding abilities with 17beta-((3)H)estradiol to the estrogen receptor proteins of the B6D2F1 mouse uterine cytosol. The concentrations of each compound required to displace 50% of the ((3)H)estradiol at 5 nM in the competitive binding assay were 1.15 nM DES, 1.09 nM 17beta-estradiol, 0.22 microM genistein, 4.00 microM daidzein, and 3.94 microM glycitein. These data indicated that glycitein has weak estrogenic activity, comparable to that of the other soy isoflavones but much lower than that of DES and 17beta-estradiol.

Animals↗

Excretion of (14)C-fumonisin B(1), (14)C-hydrolyzed fumonisin B(1), and (14)C-fumonisin B(1)-fructose in rats.

14C-Fumonisin B(1) (FB(1)) was produced by Fusarium proliferatum M-5991 in modified Myro liquid medium and purified to >95% purity with a specific activity of 1.7 mCi/mmol. Nine male and nine female F344/N rats were each dosed by gavage with 0.69 micromol of (14)C-FB(1), (14)C-hydrolyzed FB(1), or (14)C-FB(1)-fructose/kg body weight. Urinary excretion of (14)C-FB(1) and (14)C-FB(1)-fructose was 0.5% and 4.4% of the total dose, respectively, and was similar between male and female rats. Urinary excretion of (14)C-hydrolyzed HFB(1) was significantly greater (P > 0.05) in female rats as compared with male rats (17.3% vs 12.8% of the total dose, respectively). There were no significant (P > 0.05) differences in biliary excretion of the three fumonisin compounds with a mean of 1. 4% of the dose excreted at 4 h after dosing. Lesser amounts continued to be excreted up to 9.25 h after dosing. Although biliary excretion of the (14)C-FB(1), (14)C-hydrolyzed FB(1), and (14)C-FB(1)-fructose was similar, increased urinary excretion of the (14)C-hydrolyzed FB(1) as compared to (14)C-FB(1) and (14)C-FB(1)-fructose indicated a greater absorption of the hydrolyzed form.

Animals↗

Daidzein and genistein glucuronides in vitro are weakly estrogenic and activate human natural killer cells at nutritionally relevant concentrations.

Daidzein and genistein glucuronides (DG and GG), major isoflavone metabolites, may be partly responsible for biological effects of isoflavones, such as estrogen receptor binding and natural killer cell (NK) activation or inhibition. DG and GG were synthesized using 3-methylcholanthrene-induced rat liver microsomes. The Km and Vmax for daidzein and genistein were 9.0 and 7.7 micromol/L, and 0.7 and 1.6 micromol/(mg protein. min), respectively. The absence of ultraviolet absorbance maxima shifts in the presence of sodium acetate confirmed that the synthesized products were 7-O-glucuronides. DG and GG were further purified by a Sephadex LH-20 column. DG and GG competed with the binding of 17beta-(3H) estradiol to estrogen receptors of B6D2F1 mouse uterine cytosol. The concentrations required for 50% displacement of 17beta-(3H) estradiol (CB50) were: 17beta-estradiol, 1.34 nmol/L; diethylstilbestrol, 1.46 nmol/L; daidzein, 1.6 micromol/L; DG, 14.7 micromol/L; genistein, 0.154 micromol/L; GG, 7.27 micromol/L. In human peripheral blood NK cells, genistein at <0.5 micromol/L and DG and GG at 0.1-10 micromol/L enhanced NK cell-mediated K562 cancer cell killing significantly (P < 0.05). At > 0.5 micromol/L, genistein inhibited NK cytotoxicity significantly (P < 0.05). The glucuronides only inhibited NK cytotoxicity at 50 micromol/L. Isoflavones, and especially the isoflavone glucuronides, enhanced activation of NK cells by interleukin-2 (IL-2), additively. At physiological concentrations, DG and GG were weakly estrogenic, and they activated human NK cells in nutritionally relevant concentrations in vitro, probably at a site different from IL-2 action.

Adolescent↗

Urinary disposition of the soybean isoflavones daidzein, genistein and glycitein differs among humans with moderate fecal isoflavone degradation activity.

Glycitein metabolism was compared with other isoflavones to begin to understand the effect of this compound. Total isoflavones of 4.5 micromol/kg body weight from soymilk (high in genistein and daidzein) and soygerm (high in daidzein and glycitein) was fed to seven women and seven men. To minimize interindividual variation, only subjects with moderate fecal isoflavone degradation rates (half-lives of daidzein and genistein were 15.7 and 8.9 h, respectively) were included. The average 48-h urinary excretion of glycitein, daidzein and genistein was approximately 55, 46 and 29% of the dose ingested, respectively, which was significantly different from each other in men and women (P < 0.001). Plasma isoflavone concentrations at 6 and 24 h after soymilk feeding paralleled relative amounts of isoflavones in soymilk (genistein > daidzein > glycitein) (P < 0.05) in men and women, but plasma isoflavone concentrations after soygerm feeding did not parallel soygerm isoflavone concentrations in women because genistein and glycitein did not differ from each other at 6 h after feeding. Six hours after soygerm dosing, plasma isoflavone concentrations paralleled soygerm isoflavone levels in men. Based on plasma isoflavone concentrations at 6 h after dosing, the bioavailabilities of daidzein and genistein were similar in men and women. At the high glycitein dose (soygerm), plasma concentration at 24 h after dosing suggested a modest gender difference in glycitein bioavailability.

Adult↗

Low linolenate and commercial soybean oils diminish serum HDL cholesterol in young free-living adult females.

OBJECTIVE: A mutant soybean line (A16) low in linolenic acid content (2% of oil by weight) was developed to increase oil oxidative stability. It was unknown whether serum lipid and lipoprotein concentrations in humans would be affected should A16 soybean oil (A16 oil) replace commercial soybean oil in diets. This study was conducted to examine the hypothesis that in free-living normolipidemic women, the consumption of A16 oil at approximately 10% of energy intake (en%) would not affect serum lipids and lipoproteins differently than would the consumption of the same amount of a commercial soybean oil with 7% of linolenic acid content. DESIGN: Fifteen free-living female college students consumed the soybean oil daily with regular meals for 9 weeks in different orders, with each test oil being eaten for 3 weeks. During the study, 13 en% was provided by each test oil and a total of 35 en% was from dietary fat. Serum concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), low-density lipoprotein cholesterol (LDL cholesterol) and triacylglycerides (TAG) were measured. Serum total fatty acid patterns were analyzed as well. RESULTS: Each of the three test oils decreased serum total cholesterol, LDL cholesterol and TAG concentrations from the baseline values. The feeding of A16 and commercial soybean oils decreased serum HDL cholesterol significantly compared with coconut oil (p < 0.05). Dietary inclusion of coconut oil increased serum myristic acid significantly more than did either soybean oil (p < 0.01). Serum arachidonic acid concentrations were significantly greater with A16 consumption than with commercial soybean oil consumption (p < 0.001). CONCLUSION: A16 and commercial soybean oils both diminished serum HDL cholesterol. Although the fatty acid composition differed between the two soybean oils, A16 oil and commercial oil had similar effects on serum concentrations of lipoproteins and lipids. With increased oxidative stability, A16 oil is a good alternative to commercial soybean oil.

Adolescent↗

Effect of processing on fumonisin content of corn.

Fumonisins (FBs) are a family of mycotoxins produced by Fusarium moniliforme and F. proliferatum, predominant corn pathogens, and are found in most corn-containing foods. The FBs are heat stable, resistant to ammoniation, and unlike most mycotoxins, are water-soluble. The levels in corn and corn-containing foods will be presented ranging from < 20 ppb to > 2 ppm. Washing of contaminated FB-corn with water did not reduce the measured FB levels of significantly. The traditional processing step to make tortilla flour, nixtamalization [Ca(OH)2 cooking] to produce masa, reduced FB levels but produced hydrolyzed FB which was almost as toxic as FB. Retorting sweet corn in brine apparently produced hydrolyzed FB. Fermentation of corn to ethanol did not alter FB levels but distillation yielded FB-free ethanol. Attempts to enzymatically modify FB with several enzymes were unsuccessful. Reactions between FB and reducing sugars (glucose or fructose) to produce Schiff's bases yielded products that were not toxic. The effects of these processing treatments must be evaluated both chemically and biologically.

Animals↗

A diet high in wheat fiber decreases the bioavailability of soybean isoflavones in a single meal fed to women.

The absorption of some dietary components may be inhibited by dietary fiber. To study the effect of dietary fiber on the bioavailability of Isoflavones, seven healthy women were randomly assigned in a crossover design to a control diet containing 15 g dietary fiber or a wheat fiber-supplemented diet containing 40 g dietary fiber, both fed with a single dose of 0.9 mg isoflavones/kg body weight from tofu or texturized vegetable protein (TVP). The fiber-rich diet produced 55% lower plasma genistein at 24 h after soy dosing (P < 0.05) and reduced total urinary genistein by 20% (P < 0.03). Urinary daidzein was not significantly related to fiber intake. Highly insoluble, dietary wheat fiber reduced the absorption of genistein probably by its bulking effect and hydrophobic binding to this compound. Urinary genistein was greater by 23% after tofu than after TVP consumption (P < 0.02), but the percentage of ingested genistein recovered in urine was not affected by soy product intake. The higher urinary genistein after tofu consumption compared with TVP was apparently due to differences in amount of genistein between these soy foods, not the different forms of genistein present in these two soy food products.

Absorption↗

Soybean isoflavone extract suppresses early but not later promotion of hepatocarcinogenesis by phenobarbital in female rat liver.

The antioxidant and anticarcinogenic activities of soybean isoflavone extracts were investigated in female F344/rats. Diethylnitrosamine (DEN, 15 mg/kg body wt) as a cancer initiator was injected intraperitoneally into 120 female F344/N rats at 10 days of age, and at weaning, phenobarbital (PB, 500 mg/kg diet) was fed to one-half of the rats. Soybean isoflavones were extracted in acetone-0.1 N HCl and analyzed by high-performance liquid chromatography, and two levels of soybean isoflavones (920 and 1,840 mumol/kg diet) were fed during PB treatment for 3 and 11 months. Control rats were fed diets without PB and with or without isoflavones. The effect of soybean isoflavone extract on hepatic glutathione peroxidase was measured, and development of gamma-glutamyltransferase (GGT)-positive (GGT+) and placental glutathione transferase (PGST)-positive (PGST+) altered hepatic foci (AHF) was analyzed by computerized stereology. Soybean isoflavone extract providing 920 or 1,840 mumol/kg diet normalized total heptic glutathione peroxidase activity, which was suppressed about 17% by PB (p < 0.05), and both doses of isoflavone extract suppressed PB promotion of hepatocarcinogenesis, decreasing the volume occupied by GGT+ and PGST+ AHF (p < 0.05) after three months. After 11 months of PB promotion, isoflavone extract at 920 mumol/kg diet decreased PGST+ AHF compared with the PB-fed group, but neither dose of isoflavone extract suppressed development of GGT+ AHF compared with the group fed PB alone. Furthermore the control group fed isoflavone extract at 1,840 mumol/kg diet showed greater development of GGT+ and PGST+ AHF than the group fed the basal diet alone. Therefore soybean isoflavones may be anticarcinogenic, but their margin of safety is relatively narrow, with a cancer-promoting dose of 1,840 mumol/kg in female F344/N rats initiated with DEN.

Animals↗

Bioavailability of soybean isoflavones depends upon gut microflora in women.

Soybean isoflavones have been proposed to be anticarcinogenic, but their effective doses have not been established. To study their bioavailability, seven women consumed 3.4, 6.9, or 10.3 mumol isoflavones/kg body wt in soymilk in each of three meals of a liquid diet on one of three feeding days that were separated by 2-wk washout periods. Subjects were randomly assigned to doses in a cross-over design. Plasma, urine and fecal isoflavones were measured by reverse phase HPLC. In two subjects, fecal isoflavone recovery was 10-20 times that in the other five subjects. Average 48-h urinary recoveries of ingested daidzein and genistein were 16 +/- 4 and 10 +/- 4%, respectively, at all three doses among the five subjects excreting only small amounts of isoflavones in feces, whereas urinary recoveries of daidzein and genistein in the two subjects who excreted large amounts of fecal isoflavones were 32 +/- 5 and 37 +/- 6%, respectively. Urinary isoflavone excretion was nearly zero in all subjects at 48 h after dosing. Average plasma concentration of genistein at 24 h after the breakfast isoflavone dose in subjects excreting large amounts of fecal isoflavones was significantly greater by 2.5-fold than in subjects who excreted small amounts of fecal isoflavones (P < 0.05). In vitro anaerobic incubation of isoflavones with human feces showed that intestinal half-life of daidzein and genistein may be as little as 7.5 and 3.3 h, respectively. These data suggest that human isoflavone bioavailability depends upon the relative ability of gut microflora to degrade these compounds.

Adult↗

Fed before diethylnitrosamine, Fusarium moniliforme and F proliferatum mycotoxins alter the persistence of placental glutathione S-transferase-positive hepatocytes in rats.

Groups of 5-w-old F344/N female rats were fed a semipurified diet for 13 w with or without 20 mg fumonisin B1/kg provided from an aqueous extract of Fusarium moniliforme-corn culture. After 1 w, a single dose of 30 mg diethylnitrosamine (DEN)/kg was given orally. Twelve weeks later, the presence of placental glutathione S-transferase-positive (PGST-[+]) hepatocytes were immunohistochemically quantified. Rats given DEN and the FB1-containing diet for 1 or 13 w developed 4-fold more PGST-[+] hepatocytes than rats given DEN alone. In a second study, male and female F344/N rats were fed 20 mg purified FB1/kg diet or F proliferatum-corn culture material containing 20 mg FB1/kg diet for 1 w before DEN treatment. One week after DEN treatment, male rats fed the F proliferatum-corn culture material had significantly fewer PGST-[+] hepatocytes than those fed DEN with or without purified FB1. At 9 w after DEN treatment, PGST-[+] cells in female rats given DEN and fed F proliferatum-corn culture material were more persistent than in rats given DEN alone. Males given DEN and fed FB1 or F proliferatum culture material had significantly fewer PGST-[+] hepatocytes than males given DEN alone. These results suggest that F moniliforme and F proliferatum components are cocarcinogens in females. In males, however, FB1 and unidentified F proliferatum components reduced the persistence of DEN-initiated preneoplastic hepatocytes.

Administration, Oral↗

Fumonisin B1 is fetotoxic in rats.

Groups of 5-6 pregnant F344/N rats were dosed (po) from d 8 to 12 of gestation with 30 or 60 mg purified fumonisin B1 (FB1)/kg body weight, or with a fat-soluble extract of Fusarium proliferatum/corn culture derived from an amount of corn culture that would provide approximately 60 mg FB1/kg. Control rats were dosed with water or corn oil. Food intake was monitored daily during dosing. Fetal bone development was examined after staining with alizarin red, whereas internal organ development was examined in hematoxylin and eosin-stained tissue sections. Although group differences in maternal body weight were not statistically significant, weight was 6% less in dams dosed with 60 mg FB1/kg compared with the control group (p < 0.12). Relative litter weight was significantly suppressed by 60 mg FB1/kg. Ossification of the sternebrae and vertebral bodies was significantly impaired by FB1 treatment. Litters from mothers treated with a fat-soluble extract of F proliferatum/corn culture did not have suppression of weight or impairment of bone development. Fumonisin B1 is fetotoxic to rats by suppressing growth and fetal bone development.

Animals↗