Showing papers by "Thomas M. Badger published in 2004"

Not All Soy Products Are Created Equal: Caution Needed in Interpretation of Research Results

Abstract: Interest in the health benefits of soy foods has been intense among the research community, health professionals, and the public. At the same time, potential concerns associated with soy consumption, especially as related to soy isoflavones, have tempered the enthusiasm for making public health recommendations. On both accounts, the primary soybean isoflavone, genistein, has received the most attention. Because consumers are becoming increasingly confused by the often conflicting dietary messages, a balanced and accurate view of the risks and benefits of soy foods and soy food components is essential. Even among health professionals, confusion exists about proper nomenclature and about the precise composition of the agents under investigation. Levels of isoflavones are frequently assumed to be constant within categories of soy foods, and intakes are estimated rather than being directly analyzed. Furthermore, all too often research dealing singularly with genistein is interpreted by both health professionals and the media as equating directly with soy. Researchers often fail to fully understand the implications of their research outcomes and the context in which those outcomes should be placed. With the hundreds of publications yearly on soy and isoflavones, it is especially important to consider the literature in its entirety when making pronouncements about health effects. Efforts are needed by all to reduce the public confusion by adapting standardized approaches to the reporting of data. This paper provides a framework for both standardization of nomenclature and appropriate interpretation of data.

Dietary Saturated Fat Reduces Alcoholic Hepatotoxicity in Rats by Altering Fatty Acid Metabolism and Membrane Composition

Abstract: Rats fed a saturated fat diet are protected from experimentally induced alcoholic liver disease, but the molecular mechanisms underlying this phenomenon remain in dispute. We fed male Sprague-Dawley rats intragastrically by total enteral nutrition using diets with or without ethanol. In 1 control and 1 ethanol group, the dietary fat was corn oil at a level of 45% of total energy. In other groups, saturated fat [18:82 ratio of beef tallow:medium-chain triglyceride (MCT) oil] was substituted for corn oil at levels of 10, 20, and 30% of total energy, while keeping the total energy from fat at 45%. After 70 d, liver pathology, serum alanine aminotransferase (ALT), biochemical markers of oxidative stress, liver fatty acid composition, cytochrome P450 2E1 (CYP2E1) expression and activity and cytochrome P450 4A (CYP4A) expression were assessed. In rats fed the corn oil plus ethanol diet, hepatotoxicity was accompanied by oxidative stress. As dietary saturated fat content increased, all measures of hepatic pathology and oxidative stress were progressively reduced, including steatosis (P < 0.05). Thus, saturated fat protected rats from alcoholic liver disease in a dose-responsive fashion. Changes in dietary fat composition did not alter ethanol metabolism or CYP2E1 induction, but hepatic CYP4A levels increased markedly in rats fed the saturated fat diet. Dietary saturated fat also decreased liver triglyceride, PUFA, and total FFA concentrations (P < 0.05). Increases in dietary saturated fat increased liver membrane resistance to oxidative stress. In addition, reduced alcoholic steatosis was associated with reduced fatty acid synthesis in combination with increased CYP4A-catalyzed fatty acid oxidation and effects on lipid export. These findings may be important in the nutritional management and treatment of alcoholic liver disease.

Comprehensive Phytochemical Profile of Soy Protein Isolate

Abstract: Although an FDA health claim for soy protein has been issued, the potential health benefits of soy foods remain controversial among scientists, especially with regard to soy infant formula. The UV detectable isoflavones have been the focus of the majority of studies concerning health-related effects of soy protein isolate (SPI). However, the chemical identities and health effects of other SPI phytochemicals without UV absorption properties are less well-studied. In the current study, we employed liquid chromatography-tandem mass spectrometry methods to reveal a complicated phytochemical profile for SPI consisting of 136 phytochemicals. Also, we have quantitated many of these SPI phytochemicals so that dietary intakes can be estimated for foods containing SPI. On a weight/weight basis, fatty acids are the largest group of phytochemicals in the extract (64.13% total fat), followed by saponins (21.48%), and then isoflavones at 6.82%. Of the 56 lysophospholipids identified in SPI, 0.50% was lysophosphatidylcholines and 0.23% was lysophosphatidylethanolamines.

Alcoholic Liver Disease in Rats Fed Ethanol as Part of Oral or Intragastric Low-Carbohydrate Liquid Diets

Abstract: The intragastric administration of ethanol as part of a low-carbohydrate diet results in alcohol hepatotoxicity. We aimed to investigate whether comparable liver injury can be achieved by oral diet intake. Male Sprague-Dawley rats were fed ethanol as part of low-carbohydrate diets for 36-42 days either intragastrically or orally. Liver pathology, blood ethanol concentration, serum alanine amino transferase (ALT), endotoxin level, hepatic CYP2E1 induction, and cytokine profiles were assessed. Both oral and intragastric low-carbohydrate ethanol diets resulted in marked steatosis with additional inflammation and necrosis accompanied by significantly increased serum ALT, high levels of CYP2E1 expression, and production of auto-antibodies against malondialdehyde and hydroxyethyl free radical protein adducts. However, cytokine profiles differed substantially between the groups, with significantly lower mRNA expression of the anti-inflammatory cytokine interleukin 4 observed in rats fed low-carbohydrate diets orally. Inflammation and necrosis were significantly greater in rats receiving low-carbohydrate alcohol diets intragastrically than orally. This was associated with a significant increase in liver tumor necrosis factor alpha and interleukin 1beta gene expression in the intragastric model. Thus, oral low-carbohydrate diets produce more ethanol-induced liver pathology than oral high-carbohydrate diets, but hepatotoxicity is more severe when a low-carbohydrate diet plus ethanol is infused intragastrically and is accompanied by significant increases in levels of proinflammatory cytokines.

Dietary Exposure to Whey Proteins Alters Rat Mammary Gland Proliferation, Apoptosis, and Gene Expression during Postnatal Development

Abstract: We have found that AIN-93G diets made with whey protein hydrolysate (WPH) reduce 7,12-dimethyl-benz[a]anthracene (DMBA)-induced tumor incidence in Sprague-Dawley (Harlan) rats relative to those fed a diet with casein (CAS). Herein, we replicated these findings in another Sprague-Dawley substrain (Charles River) and examined whether WPH protective effects were associated with altered mammary gland differentiation status and expression of the tumor suppressor phosphatase and tensin homolog deleted in chromosome ten (PTEN). Mammary tumor incidence was lower in DMBA-treated rats fed WPH than in those fed CAS. Mammary glands of WPH- and CAS-fed rats were isolated at weaning [postnatal day (PND) 21-28] and at an early adult stage (PND 50-53) and analyzed for proliferative (proliferating cell nuclear antigen immunoreactivity), apoptotic (terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick-end labeling), and differentiation (beta-casein) indices, as well as for PTEN mRNA and protein levels. PND 50-53 rats fed WPH showed decreased proliferation and increased apoptosis in mammary structures, coincident with increased mammary beta-casein gene expression, decreased terminal end-bud numbers, and increased ductal lengths, relative to same-age CAS-fed rats. When challenged with DMBA for 24 h, mammary glands of PND 53 CAS-fed rats had decreased cell survival in both terminal end buds and ductal epithelium, while the mammary glands of WPH-fed rats were not altered from pre-DMBA levels. At 7 d post-DMBA, mammary glands of CAS- and WPH-fed rats exhibited comparable apoptotic indices. Mammary PTEN expression was higher in WPH- than in CAS-fed rats at PND 21-28, but was not different in young adults fed either diet. Results demonstrate that dietary WPH advances mammary gland differentiation during neonatal development and suggest that the transiently increased expression of the pro-apoptotic signal PTEN during a sensitive developmental window may partly underlie the cancer protective effects of WPH.

Feeding of soy protein isolate to rats during pregnancy and lactation suppresses formation of aberrant crypt foci in their progeny's colons: interaction of diet with fetal alcohol exposure.

Abstract: Soy protein isolate (SPI) in the diet may inhibit colon tumorigenesis. We examined azoxymethane (AOM)-induced aberrant crypt foci (ACF) in male rats in relation to lifetime, pre-weaning, or post-weaning dietary exposure to SPI and also within the context of fetal alcohol exposure. Pregnant Sprague Dawley rats were fed AIN-93G diets containing casein (20%, the control diet) or SPI (20%) as the sole protein source starting on gestation day 4 (GD 4). Progeny were weaned on postnatal day (PND) 21 to the same diet as their dams and were fed this diet until termination of the experiment at PND 138. Rats received AOM on PND 89 and 96. Lifetime (GD 4 to PND 138) feeding of SPI led to reduced frequency of ACF with 4 or more crypts in the distal colon. Progeny of dams fed SPI only during pregnancy and lactation or progeny fed SPI only after weaning exhibited similarly reduced frequency of large ACF in distal colon. Number of epithelial cells, in the distal colon, undergoing apoptosis was unaffected by diet. SPI reduced weight gain and adiposity, but these were not correlated with fewer numbers of large ACF. Lifetime SPI exposure similarly inhibited development of large ACF in Sprague Dawley rats whose dams were exposed to ethanol during pregnancy. In summary, feeding of SPI to rat dams during pregnancy and lactation suppresses numbers of large ACF in their progeny, implying a long-term or permanent change elicited by the maternal diet. Moreover, results support the use of ACF as an intermediate endpoint for elucidating effects of SPI and its biochemical constituents in colon cancer prevention in rats.

Diets containing soy protein isolate increase Hepatic CYP3A expression and inducibility in weanling male rats exposed during early development

Abstract: Hepatic CYP3A enzymes were studied in weanling male Sprague-Dawley rats exposed to diets from gestational d 4 in which the sole protein source was either casein (CAS) or soy protein isolate (SPI). At age 25 d, rats were gavaged with corn oil or one of the CYP3A inducers, dexamethasone (DEX) and clotrimazole (CLT), at a dose of 50 mg/kg. Little CYP3A1 (CYP3A23), CYP3A2, or CYP3A9 mRNA was observed in CAS-fed weanling rats but CYP3A18 mRNA was readily detectable in Northern blots. In contrast, consumption of SPI without inducer treatment resulted in the expression of CYP3A1 (CYP3A23), and CYP3A2 mRNAs, expression of CYP3A apoprotein in hepatic microsomes, and a 2-fold greater turnover of the CYP3A substrate midazolam (P < 0.05). DEX induced CYP3A1, CYP3A2, and CYP3A9 (P < 0.05), but not CYP3A18 mRNA expression in rats fed both diets. Hepatic CYP3A apoprotein expression and midazolam 4-hydroxylation in SPI-fed rats was greater than that of CAS-fed rats after DEX treatment (P < 0.05). CLT also induced CYP3A2 mRNA 2-fold in rats fed both diets but CYP3A apoprotein expression in microsomes from SPI-fed CLT rats was double that of CLT-treated rats fed CAS (P < 0.05). The elevation of CYP3A apoprotein due to SPI and the CYP3A apoprotein induction by DEX and CLT treatment yielded no significant diet x inducer interaction. Analysis of heterologous nuclear RNA expression by RT-PCR using intron-specific primers for CYP3A1 revealed a 14-fold increase in RNA transcription in CAS-fed rats after treatment with DEX (P < 0.05) but no increase in rats fed SPI compared with rats fed CAS even though CYP3A1 mRNA and CYP3A apoprotein were significantly elevated. These data demonstrate that exposure to SPI during early development can increase CYP3A expression via post-transcriptional mechanisms and suggest that early soy consumption has potential effects on the metabolism of a wide variety of CYP3A substrates.