Showing papers in "Journal of Nutritional Biochemistry in 2003"
TL;DR: This paper will review the recent literature that describes functional properties of essential amino acids, whey proteins, wheY-derived minerals and other compounds and the mechanisms by which they may confer benefits to active people in the context that exercise is a form of metabolic stress.
Abstract: Whey proteins and amino acid supplements have a strong position in the sports nutrition market based on the purported quality of proteins and amino acids they provide. Recent studies employing stable isotope methodology demonstrate the ability of whey proteins or amino acid mixtures of similar composition to promote whole body and muscle protein synthesis. Other developing avenues of research explore health benefits of whey that extend beyond protein and basic nutrition. Many bioactive components derived from whey are under study for their ability to offer specific health benefits. These functions are being investigated predominantly in tissue culture systems and animal models. The capacity of these compounds to modulate adiposity, and to enhance immune function and anti-oxidant activity presents new applications potentially suited to the needs of those individuals with active lifestyles. This paper will review the recent literature that describes functional properties of essential amino acids, whey proteins, whey-derived minerals and other compounds and the mechanisms by which they may confer benefits to active people in the context that exercise is a form of metabolic stress. The response to this stress can be positive, as with the accretion of more muscle and improved functionality or greater strength. However, overall benefits may be compromised if immune function or general health is challenged in response to the stress. From a mechanistic standpoint, whey proteins, their composite amino acids, and/or associated compounds may be able to provide substrate and bioactive components to extend the overall benefits of physical activity.
439 citations
TL;DR: It is suggested that one of the underlying mechanisms by which EGCG affects lipid metabolism is by interfering with the micellar solubilization of cholesterol in the digestive tract, which then in turn decreased cholesterol absorption.
Abstract: Catechins, compounds derived from green tea, have been shown to reduce plasma cholesterol levels and the rate of cholesterol absorption. We investigated the dose response and the mechanism of action of epigallocatechin gallate (EGCG) on these parameters in rats. Wistar rats were fed a diet high in cholesterol and fat containing either none, 0.25% (0.2 g/day/kg BW), 0.5% (0.4 g/day/kg/BW) or 1.0% (0.7 g/day/kg BW) of EGCG. After 4 weeks of treatment, total cholesterol and low density lipoprotein plasma levels were significantly reduced in the group fed 1% EGCG when compared to the no treatment group. Plasma triglycerides and high-density lipoprotein levels did not change significantly. Following a single oral application of a liquid test-meal, intestinal cholesterol absorption in Wistar rats was 79.3% in the control group. In the group treated with 0.1 g/kg BW EGCG intestinal cholesterol absorption decreased to 73.7% and in the group treated with 0.5 g/kg BW of EGCG intestinal cholesterol absorption fell significantly to 62.7% (P = 0.005). Total fat absorption was very efficient in the control group (99.5% of the applied dose) and decreased significantly but moderately in the group treated with the highest doses of EGCG (0.75, 1 g/kg BW). In an in-vitro biliary micelle model, the addition of 55 microM to 1300 microM EGCG not only decreased cholesterol solubility dose-dependently in these micelles but also altered the size of the mixed lecithin/taurocholate/cholesterol micelles as demonstrated by light scattering. This study provides evidence suggesting that the cholesterol-lowering effect of green tea is mainly elicited by EGCG, one of the most abundant catechins contained in green tea. It is suggested that one of the underlying mechanisms by which EGCG affects lipid metabolism is by interfering with the micellar solubilization of cholesterol in the digestive tract, which then in turn decreased cholesterol absorption.
401 citations
TL;DR: In this paper, plant sterols and stanols, which are structurally related to cholesterol, decrease the incorporation of dietary and biliary cholesterol into micelles, which leads to decreased serum LDL cholesterol concentrations.
Abstract: High serum LDL cholesterol concentration is a major risk factor for cardiovascular complications. This risk can be lowered by diet. In this respect foods containing plant sterol or stanol esters can be useful for mildly- and hypercholesteraemic subjects. Plant sterols and stanols, which are structurally related to cholesterol, decrease the incorporation of dietary and biliary cholesterol into micelles. This lowers cholesterol absorption. Furthermore, these components increase ABC-transporter expression, which may also contribute to the decreased cholesterol absorption. Consequently, cholesterol synthesis and LDL receptor activity increase, which ultimately leads to decreased serum LDL cholesterol concentrations. Animal studies have further shown that these dietary components may also lower atherosclerotic lesion development. Plant sterols and stanols also lower plasma lipid-standardized concentrations of the hydrocarbon carotenoids, but not those of the oxygenated cartenoids and tocopherols. Also, vitamin A and D concentrations are not affected. Although absorption of plant sterols and stanols (0.02-3.5%) is low compared to cholesterol (35-70%), small amounts are found in the circulation and may influence other physiological functions. However, there is no consistent evidence that plant sterols or stanols can change the risk of colon or prostate cancer, or immune status. In conclusion, plant sterols and stanols effectively reduce serum LDL cholesterol and atherosclerotic risk. In addition potential effects of plant sterols and stanols on other metabolic processes remain to be elucidated.
280 citations
TL;DR: In a randomized crossover study in healthy men on a low-polyphenol diet, the authors determined the effects of 2 polyphenol-rich juices (330 ml/d) supplemented for 2 weeks on bioavailability of polyphenols, markers of antioxidative and immune status, and reduction of DNA damage.
Abstract: Polyphenolic compounds exert a variety of physiological effects in vitro including antioxidative, immunomodulatory and antigenotoxic effects. In a randomized crossover study in healthy men on a low-polyphenol diet, we determined the effects of 2 polyphenol-rich juices (330 ml/d) supplemented for 2 weeks on bioavailability of polyphenols, markers of antioxidative and immune status, and reduction of DNA damage. Juices provided 236 mg (A) and 226 mg (B) polyphenols with cyanidin glycosides (A) and epigallocatechin gallate (B) as major polyphenolic ingredients. There was no accumulation of plasma polyphenols after two weeks of juice supplementation. In contrast, plasma malondialdehyde decreased with time during juice interventions. Moreover, juice consumption also increased lymphocyte proliferative responsiveness, with no difference between the two juices. Interleukin-2 secretion by activated lymphocytes and the lytic activity of natural killer cells were significantly increased by both juices. Juice intervention had no effect on single DNA strand breaks, but significantly reduced oxidative DNA damage in lymphocytes. A time-delay was observed between the intake of fruit juice and the reduction of oxidative DNA damage and the increase in interleukin-2 secretion. We conclude that consumption of either juice enhanced antioxidant status, reduced oxidative DNA damage and stimulated immune cell functions. However, fruit juice consumption for 2 weeks did not result in elevated plasma polyphenols in subjects after overnight fasting. Further studies should focus on the time-delay between juice intake and changes in measured physiological functions, as well as on active polyphenolic metabolites mediating the observed effects.
238 citations
TL;DR: Results suggest that after 14 days of treatment with an appropriate pharmacological dose, α-lipoic acid may reduce oxidative stress in STZ-induced diabetic rats, perhaps by modulating the thiol status of the cells.
Abstract: Increased oxidative stress and impaired antioxidant defense mechanisms are important factors in the pathogenesis and progression of diabetes mellitus and other oxidant-related diseases. This study was designed to determine whether α-lipoic acid, which has been shown to have substantial antioxidant properties, when administered (10 mg/kg ip) once daily for 14 days to normal and diabetic female Sprague-Dawley rats would prevent diabetes-induced changes in biomarkers of oxidative stress in liver, kidney and heart. Serum glucose concentrations, aspartate aminotransferase activity, and glycated hemoglobin levels, which were increased in diabetes, were not significantly altered by α-lipoic acid treatment. Normal rats treated with a high dose of α-lipoic acid (50 mg/kg) survived but diabetic rats on similar treatment died during the course of the experiment. The activity of glutathione peroxidase was increased in livers of normal rats treated with α-lipoic acid, but decreased in diabetic rats after α-lipoic acid treatment. Hepatic catalase activity was decreased in both normal and diabetic rats after α-lipoic acid treatment. Concentrations of reduced glutathione and glutathione disulfide in liver were increased after α-lipoic acid treatment of normal rats, but were not altered in diabetics. In kidney, glutathione peroxidase activity was elevated in diabetic rats, and in both normal and diabetic animals after α-lipoic acid treatment. Superoxide dismutase activity in heart was decreased in diabetic rats but normalized after treatment with α-lipoic acid; other cardiac enzyme activities were not influenced by either diabetes or antioxidant treatment. These results suggest that after 14 days of treatment with an appropriate pharmacological dose, α-lipoic acid may reduce oxidative stress in STZ-induced diabetic rats, perhaps by modulating the thiol status of the cells.
226 citations
TL;DR: Phytochemicals can either scavenge the constitutive H2O2 or paradoxically generate additional amounts of H2 O2 to inhibit the proliferation of cancer cells.
Abstract: Phytochemicals are potential cancer chemopreventive agents, based partly on cellular research establishing that phytochemicals inhibit the proliferation of cancer cells. To elucidate the mechanism of phytochemicals, a basic understanding is needed of what stimulates cancer cell proliferation. Cancer cells, particularly those that are highly invasive or metastatic, may require a certain level of oxidative stress to maintain a balance between undergoing either proliferation or apoptosis. They constitutively generate large but tolerable amounts of H2O2 that apparently function as signaling molecules in the mitogen-activated protein kinase pathway to constantly activate redox-sensitive transcription factors and responsive genes that are involved in the survival of cancer cells as well as their proliferation. With such a reliance of cancer cells on H2O2, it follows that if the excess H2O2 can be scavenged by phenolic phytochemicals having antioxidant activity, the oxidative stress-responsive genes can be suppressed and consequently cancer cell proliferation inhibited. On the other hand, phenolic phytochemicals and another group of phytochemicals known as isothiocyanates can induce the formation of H2O2 to achieve an intolerable level of high oxidative stress in cancer cells. As an early response, the stress genes are activated. However, when the critical threshold for cancer cells to cope with the induced oxidative stress has been reached, key cellular components such as DNA are damaged irreparably. In conjunction, genes involved in initiating cell cycle arrest and/or apoptosis are activated. Therefore, phytochemicals can either scavenge the constitutive H2O2 or paradoxically generate additional amounts of H2O2 to inhibit the proliferation of cancer cells.
217 citations
TL;DR: Dietary combination of the mineral nutrients and plant sterols provides a promising novel approach to the modification of cardiovascular risk factors with specific focus on the effects of calcium.
Abstract: High serum cholesterol, hypertension and obesity are major risk factors for cardiovascular diseases, and together with insulin resistance form a deadly disorder referred to as the metabolic syndrome. All the aspects of this syndrome are strongly related to dietary and lifestyle factors; therefore, it would be reasonable to look for dietary approaches to their modification. Mineral nutrients, such as calcium, potassium and magnesium, lower blood pressure, and especially calcium has beneficial effects also on serum lipids. Recent evidence suggests that increased intake of calcium may help in weight control as well. This review summarizes previous literature on the effects and use of dietary minerals on serum lipids, blood pressure and obesity, with specific focus on the effects of calcium. Calcium and magnesium as divalent cations can form insoluble soaps with fatty acids in the intestine and thus prevent the absorption of part of the dietary fat. Decreased absorption of saturated fat leads to reduction in serum cholesterol level via decreased production of VLDL and increased intake of LDL in the liver. Dietary calcium may also bind bile acids, which increases the conversion of cholesterol to bile acids in the liver. Furthermore, calcium appears to enhance the cholesterol-lowering effect of plant sterols. Thus, dietary combination of the mineral nutrients and plant sterols provides a promising novel approach to the modification of cardiovascular risk factors.
199 citations
TL;DR: The advantages of the Mediterranean diet rich in olive oil and fish on atherosclerosis may be due to the modulation of the cellular oxidative stress/antioxidant status, the modification of lipoproteins and the down-regulation of inflammatory mediators.
Abstract: Atherosclerosis is the principal contributor to the pathogenesis of myocardial and cerebral infarction, gangrene and loss of function in the extremities. It results from an excessive inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. Atherosclerotic lesions develop fundamentally in three stages: dysfunction of the vascular endothelium, fatty streak formation and fibrous cap formation. Each stage is regulated by the action of vasoactive molecules, growth factors and cytokines. This multifactorial etiology can be modulated through the diet. The degree of unsaturation of dietary fatty acids affects lipoprotein composition as well as the expression of adhesion molecules and other pro-inflammatory factors, and the thrombogenicity associated with atherosclerosis development. Thus, the preventive effects of a monounsaturated-fatty acid-rich diet on atherosclerosis may be explained by the enhancement of high-density lipoprotein-cholesterol levels and the impairment of low-density lipoprotein-cholesterol levels, the low-density lipoprotein susceptibility to oxidation, cellular oxidative stress, thrombogenicity and atheroma plaque formation. On the other hand, the increase of high-density lipoprotein cholesterol levels and the reduction of thrombogenicity, atheroma plaque formation and vascular smooth muscle cell proliferation may account for the beneficial effects of polyunsaturated fatty acid on the prevention of atherosclerosis. Thus, the advantages of the Mediterranean diet rich in olive oil and fish on atherosclerosis may be due to the modulation of the cellular oxidative stress/antioxidant status, the modification of lipoproteins and the down-regulation of inflammatory mediators.
198 citations
TL;DR: Evidence is provided to extend the role of niacin as a lipid-lowering drug beyond its role as a vitamin.
Abstract: Niacin has been widely used as a pharmacologic agent to regulate abnormalities in plasma lipid and lipoprotein metabolism and in the treatment of atherosclerotic cardiovascular disease Although the use of niacin in the treatment of dyslipidemia has been reported as early as 1955, only recent studies have yielded an understanding about the cellular and molecular mechanism of action of niacin on lipid and lipoprotein metabolism In brief, the beneficial effect of niacin to reduce triglycerides and apolipoprotein-B containing lipoproteins (eg, VLDL and LDL) are mainly through: a) decreasing fatty acid mobilization from adipose tissue triglyceride stores, and b) inhibiting hepatocyte diacylglycerol acyltransferase and triglyceride synthesis leading to increased intracellular apo B degradation and subsequent decreased secretion of VLDL and LDL particles The mechanism of action of niacin to raise HDL is by decreasing the fractional catabolic rate of HDL-apo AI without affecting the synthetic rates Additionally, niacin selectively increases the plasma levels of Lp-AI (HDL subfraction without apo AII), a cardioprotective subfraction of HDL in patients with low HDL Using human hepatocytes (Hep G2 cells) as an in vitro model system, recent studies indicate that niacin selectively inhibits the uptake/removal of HDL-apo AI (but not HDL-cholesterol ester) by hepatocytes, thereby increasing the capacity of retained HDL-apo AI to augment cholesterol efflux through reverse cholesterol transport pathway The studies discussed in this review provide evidence to extend the role of niacin as a lipid-lowering drug beyond its role as a vitamin
161 citations
TL;DR: This review summarizes the results of recent studies on the associations of common gene variants with multifactorial chronic conditions strongly affected by nutritional factors and suggests several new directions emerge as targets of research on the role of genetic variation in relation to diet and complex chronic diseases.
Abstract: Rapid progress in human genome decoding has accelerated search for the role of gene polymorphisms in the pathogenesis of complex multifactorial diseases This review summarizes the results of recent studies on the associations of common gene variants with multifactorial chronic conditions strongly affected by nutritional factors Three main individual sections discuss genes related to energy homeostasis regulation and obesity, cardiovascular disease (CVD), and cancer It is evident that several major chronic diseases are closely related (often through obesity) to deregulation of energy homeostasis Multiple polymorphic genes encoding central and peripheral determinants of energy intake and expenditure have been revealed over the past decade Food intake control may be affected by polymorphisms in the genes encoding taste receptors and a number of peripheral signaling peptides such as insulin, leptin, ghrelin, cholecystokinin, and corresponding receptors Polymorphic central regulators of energy intake include hypothalamic neuropeptide Y, agouti-related protein, melanocortin pathway factors, CART (cocaine- and amphetamine-regulated transcript), some other neuropeptides, and receptors for these molecules Potentially important polymorphisms in the genes encoding energy expenditure modulators (alpha- and beta- adrenoceptors, uncoupling proteins, and regulators of adipocyte growth and differentiation) are also discussed CVD-related gene polymorphisms comprising those involved in the pathogenesis of atherosclerosis, blood pressure regulation, hemostasis control, and homocysteine metabolism are considered in a separate section with emphasis on multiple polymorphisms affecting lipid transport and metabolism and their interactions with diet Cancer-associated polymorphisms are discussed for groups of genes encoding enzymes of xenobiotic metabolism, DNA repair enzymes, factors involved in the cell cycle control, hormonal regulation-associated proteins, enzymes related to DNA methylation through folate metabolism, and angiogenesis-related factors There is an apparent progress in the field with hundreds of new gene polymorphisms discovered and characterized, however firm evidence consistently linking them with pathogenesis of complex chronic diseases is still limited Ways of improving the efficiency of candidate gene approach-based studies are discussed in a short separate section Successful unraveling of interaction between dietary factors, polymorphisms, and pathogenesis of several multifactorial diseases is exemplified by studies of folate metabolism in relation to CVD and cancer It appears that several new directions emerge as targets of research on the role of genetic variation in relation to diet and complex chronic diseases Regulation of energy homeostasis is a fundamental problem insufficiently investigated in this context so far Impacts of genetic variation on systems controlling angiogenesis, inflammatory reactions, and cell growth and differentiation (comprising regulation of the cell cycle, DNA repair, and DNA methylation) are also largely unknown and need thorough analysis These goals can be achieved by complex simultaneous analysis of multiple polymorphic genes controlling carefully defined and selected elements of relevant metabolic and regulatory pathways in meticulously designed large-scale studies
160 citations
TL;DR: This review will discuss fatty acid-mediated regulation of nuclear receptors, focusing on peroxisome proliferators-activated receptors (PPARs), liver X receptors, retinoid X receptors (RXRs), and Hepatocyte Nuclear Factor alpha (HNF-4alpha), all of which play pivotal roles in dietary fatty acids-mediated effects.
Abstract: Long chain fatty acids, derived either from endogenous metabolism or by nutritional sources play significant roles in important biological processes of membrane structure, production of biologically active compounds, and participation in cellular signaling processes. Recently, the structure of dietary fatty acids has become an important issue in human health because ingestion of saturated fats (containing triglycerides composed of saturated fatty acids) is considered harmful, while unsaturated fats are viewed as beneficial. It is important to note that the molecular reason for this dichotomy still remains elusive. Since fatty acids are important players in development of pathology of cardiovascular and endocrine system, understanding the key molecular targets of fatty acids, in particular those that discriminate between saturated and unsaturated fats, is much needed. Recently, insights have been gained on several fatty acid-activated nuclear receptors involved in gene expression. In other words, we can now envision long chain fatty acids as regulators of signal transduction processes and gene regulation, which in turn will dictate their roles in health and disease. In this review, we will discuss fatty acid-mediated regulation of nuclear receptors. We will focus on peroxisome proliferators-activated receptors (PPARs), liver X receptors (LXR), retinoid X receptors (RXRs), and Hepatocyte Nuclear Factor alpha (HNF-4α), all of which play pivotal roles in dietary fatty acid-mediated effects. Also, the regulation of gene expression by Conjugated Linoleic Acids (CLA), a family of dienoic fatty acids with a variety of beneficial effects, will be discussed. Keywords : Fatty acid; Nuclear receptor; Gene; Transcription
TL;DR: In this article, a large body of evidence suggests that post-exercise lipemia can be attenuated following an individual exercise session, with the energy expended during exercise being an important determinant of the extent of TG lowering.
Abstract: Endurance trained people exhibit low levels of postprandial lipemia. However, this favorable situation is rapidly reversed with de-training and it is likely that the triglyceride (TG) lowering effects of exercise are mainly the result of acute metabolic responses to recent exercise rather than long-term training adaptations. A large body of evidence suggests that postprandial lipemia can be attenuated following an individual exercise session, with the energy expended during exercise being an important determinant of the extent of TG lowering. Increased lipoprotein lipase-mediated TG clearance and reduced hepatic TG secretion are both likely to contribute to the exercise-induced TG reductions. These changes may occur in response to post-exercise substrate deficits in skeletal muscle and/or the liver. In addition, regular exercise can oppose the hypertriglyceridaemia sometimes seen with low-fat, high-carbohydrate diets. Levels of physical activity should therefore be taken into account when considering nutritional strategies for reducing the risk of cardiovascular disease.
TL;DR: Extra Virgin olive oil has high organoleptic properties and the highest antioxidant activity, which makes this oil a preferable choice for diseases preventing diets.
Abstract: The aim of this study was to compare the contents of the main biochemical compounds and the antioxidant capacity of five Spanish olive oils by four different antioxidant tests and to find out the most valuable oil for disease preventing diets. Fatty acids, sterols and individual antioxidant compounds in Arbequina, Hojiblanca, Extra Virgin, Picual and Lampante Spanish olive oils were determined. Antioxidant activities were done as well using different radical scavenging activities: total radical-trapping antioxidative potential by ABAP (TRAP-ABAP), radical scavenging activity by DPPH (RSA-DPPH), antioxidant assay by beta-carotene-linoleate model system (AA-beta-carotene) and total antioxidant status by ABTS (TAA-ABTS). The highest content of all studied antioxidant compounds (353; 329; 4.6 and 2.7 mg/kg for tocopherols, tocotrienols, polyphenols and o-diphenols, respectively) was found in Extra Virgin oil. Also the highest antioxidant capacity was observed in Extra Virgin oil (668 nM/ml; 29.4%; 40.4% and 2.64 mM TE/kg for TRAP-ABAP, RSA-DPPH, AA- beta-carotene and TAA-ABTS, respectively). The correlation between total phenols and antioxidant capacities measured by four methods was very high, but the highest for the beta-carotene (R = 0.9958). In conclusion, the best method for determination of the antioxidant capacity of olive oils is the beta-carotene test. Extra Virgin olive oil has high organoleptic properties and the highest antioxidant activity. The above-mentioned makes this oil a preferable choice for diseases preventing diets.
TL;DR: It is suggested that dietary fish oil may decrease the risk for cardiovascular disease through the modulation of both plasma lipids and inflammatory markers in healthy postmenopausal women.
Abstract: Background: Atherogenesis is a complex process involving both a low-grade inflammation and a disturbed lipid profile. Although dietary fish and fish oil improve the latter of these two risk factors, their impact on the former is less clear. Objective: This study addressed the effect of supplementation with fish oil in doses achievable with diet on serum C-reactive protein (CRP), interleukin-6 (IL-6), and the lipid profile. Methods and results: Thirty healthy subjects taking HRT were randomly divided into three groups and supplemented for five weeks with 14g/day safflower oil (SO), 7g/day of both safflower oil and fish oil (LFO), or 14g/day fish oil (HFO). Measurements included serum high-sensitivity CRP, IL-6 in plasma and in cell culture supernatant collected from 24-hr lipopolysaccharide (LPS)-stimulated whole blood, and lipid profile markers. CRP and IL-6 were adjusted for body mass index (BMI). Fish oil supplementation significantly decreased CRP and IL-6 compared to SO, with a greater effect in the LFO than HFO groups. Plasma triacylglycerol (TG) and the TG/HDL-C ratio were significantly lower in the HFO compared to the SO group. Conclusions: These results suggest that dietary fish oil may decrease the risk for cardiovascular disease through the modulation of both plasma lipids and inflammatory markers in healthy postmenopausal women.
TL;DR: Observations that biotin metabolites that have been considered "metabolic waste" in previous studies might have biotin-like activities are likely to lead to a better understanding of roles for biotin in cell biology and fetal development.
Abstract: In mammals, biotin serves as coenzyme for four carboxylases, which play essential roles in the metabolism of glucose, amino acids, and fatty acids. Biotin deficiency causes decreased rates of cell proliferation, impaired immune function, and abnormal fetal development. Evidence is accumulating that biotin also plays an important role in regulating gene expression, mediating some of the effects of biotin in cell biology and fetal development. DNA microarray studies and other gene expression studies have suggested that biotin affects transcription of genes encoding cytokines and their receptors, oncogenes, genes involved in glucose metabolism, and genes that play a role in cellular biotin homeostasis. In addition, evidence has been provided that biotin affects expression of the asialoglycoprotein receptor and propionyl-CoA carboxylase at the post-transcriptional level. Various pathways have been identified by which biotin might affect gene expression: activation of soluble guanylate cyclase by biotinyl-AMP, nuclear translocation of NF-kappaB (in response to biotin deficiency), and remodeling of chromatin by biotinylation of histones. Some biotin metabolites that cannot serve as coenzymes for carboxylases can mimic biotin with regard to its effects on gene expression. This observation suggests that biotin metabolites that have been considered "metabolic waste" in previous studies might have biotin-like activities. These new insights into biotin-dependent gene expression are likely to lead to a better understanding of roles for biotin in cell biology and fetal development.
TL;DR: It appeared that green tea exerts potent body fat-suppressive effects in rats fed on a high-fat diet and the effect was resulted in part from reduction in digestibility and to much greater extent from increase in brown adipose tissue thermogenesis through beta-adrenoceptor activation.
Abstract: The aim of the present study was to investigate body fat-suppressive effects of green tea in rats fed on a high-fat diet and to determine whether the effect is associated with β-adrenoceptor activation of thermogenesis in brown adipose tissue. Feeding a high-fat diet containing water extract of green tea at the concentration of 20g/kg diet prevented the increase in body fat gain caused by high-fat diet without affecting energy intake. Energy expenditure was increased by green tea extract which was associated with an increase in protein content of interscapular brown adipose tissue. The simultaneous administration of the β-adrenoceptor antagonist propranolol(500 mg/kg diet) inhibited the body fat-suppressive effect of green tea extract. Propranolol also prevented the increase in protein content of interscapular brown adipose tissue caused by green tea extract. Digestibility was slightly reduced by green tea extract and this effect was not affected by propranolol. Therefore it appeared that green tea exerts potent body fat-suppressive effects in rats fed on a high-fat diet and the effect was resulted in part from reduction in digestibility and to much greater extent from increase in brown adipose tissue thermogenesis through β-adrenoceptor activation.
TL;DR: The data indicate that supplementation with Cassia auriculata leaf extract can offer protection against free radical mediated oxidative stress in experimental hepatotoxicity and histopathological studies of the liver and brain confirmed the beneficial role of Cassia AuriculATA leaf extract.
Abstract: This study was undertaken to investigate the effect of Cassia auriculata leaf extract on tissue lipid peroxidation and antioxidant status in experimental hepatotoxicity. Administering ethanol to rats for 60 days resulted in significantly elevated levels of serum total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) as compared with those of the experimental control rats. Significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), hydroperoxides and lowered activities of superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) were also observed on alcohol treatment as compared with those of experimental control rats. Concentration of serum non-enzymic antioxidants such as vitamin E and vitamin C were also significantly lowered on alcohol supplementation. Treatment with Cassia auriculata leaf extract at a dose of 250 mg kg −1 body weight and 500 mg kg −1 body weight to rats administered alcohol, lowered the levels of TBARS and hydroperoxides and elevated the activities of SOD and CAT and the levels of reduced GSH in the liver, brain, kidney and intestine significantly compared to unsupplemented alcohol treated rats. Cassia auriculata leaf extract treatment restored the serum vitamin E, and vitamin C levels also to near those of the experimental control animals. Our data indicate that supplementation with Cassia auriculata leaf extract can offer protection against free radical mediated oxidative stress in experimental hepatotoxicity. In addition, histopathological studies of the liver and brain confirmed the beneficial role of Cassia auriculata leaf extract.
TL;DR: In this paper, the effects of SAMe on liver injury in mice induced by acute alcohol administration were investigated, and the results showed that SAMe treatment significantly attenuated the liver injury.
Abstract: Although S-Adenosylmethionine (SAMe) has beneficial effects in many hepatic disorders, the effects of SAMe on acute alcohol-induced liver injury are unknown. In the present study, we investigated effects of SAMe on liver injury in mice induced by acute alcohol administration. Male C57BL/6 mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. SAMe (5 mg/kg BW) was administrated i.p. once a day for three days before ethanol administration. Subsequent serum ALT level, hepatic lipid peroxidation, enzymatic activity of CYP2E1 and hepatic mitochondrial glutathione levels were measured colorimetrically. Intracellular SAMe concentration was measured by high-performance liquid chromatography (HPLC). Histopathological changes were assessed by H&E staining. Our results showed that acute ethanol administration caused prominent microvesicular steatosis with mild necrosis and an elevation of serum ALT activity. SAMe treatment significantly attenuated the liver injury. In association with the hepatocyte injury, acute alcohol administration induced significant decreases in both hepatic SAMe and mitochondrial GSH levels along with enhanced lipid peroxidation. SAMe treatment attenuated hepatic SAMe and mitochondrial GSH depletion and lipid peroxidation following acute alcohol exposure. These results demonstrate that SAMe protects against the liver injury and attenuates the mitochondrial GSH depletion caused by acute alcohol administration. SAMe may prove to be an effective therapeutic agent in many toxin-induced liver injuries including those induced by alcohol.
TL;DR: The marked body weight loss by inducing diabetes was not recovered by feeding resistant starch, even though there are no differences in food intakes compared to the non-diabetic control rats.
Abstract: To examine the effect of two types of resistant starch on blood glucose and insulin levels, colonic events, hypolipidemic actions and humoral immune responses, Sprague-Dawley streptozotocin-induced diabetic rats were fed diet containing resistant starch from corn or rice. The marked body weight loss by inducing diabetes was not recovered by feeding resistant starch, even though there are no differences in food intakes compared to the non-diabetic control rats. No significant effect of resistant starch feeding on blood glucose and insulin was found. Even though the length of small intestines, and cecum, colon and rectum together with the tissue weight of cecum were not affected by feeding resistant starch, the intestinal transit time was markedly shortened by both types of resistant starch and resistant starch from corn had a more pronounced effect. The short chain fatty acids in the intestinal contents did not appear to be different among the groups. Nonetheless, both of resistant starch from corn and rice significantly lowered plasma total lipid and cholesterol concentrations compared to the diabetic control. The total liver cholesterol lowering effect was observed with resistant starch from rice. Neither immunoglobulin G nor C(3) were influenced by resistant starch.
TL;DR: This 200-day treatment significantly reduced serum triglycerides and atherosclerotic index (ratio of non-HDL-cholesterol to HDL-ch cholesterol) and Severity of atherosclerosis was reduced significantly in all treatment groups.
Abstract: Long-term effects of Cholestin (Monascus purpureus rice; red yeast rice) on serum lipids and severity of atherosclerosis were examined in rabbits fed for 200 days on a semi-purified diet containing 0.25% cholesterol. Serum total cholesterol was 25 and 40% lower, respectively, in rabbits fed 0.4 or 1.35 g/kg/day of Cholestin (Monascus purpureus rice; red yeast rice) compared to controls. This treatment also lowered serum LDL cholesterol. This 200-day treatment significantly reduced serum triglycerides and atherosclerotic index (ratio of non-HDL-cholesterol to HDL-cholesterol). Although similar reductions of total, LDL-cholesterol and triglycerides were observed, a parallel group of rabbits fed lovastatin (0.0024 g/kg/day) failed to reduce the index significantly. Apolipoprotein A(1) was increased and apolipoprotein B was reduced in all treatment groups. Severity of atherosclerosis was reduced significantly in all treatment groups. The sudanophilic area of involvement was 80.6% in controls, and reduced significantly; to 30.1% on the low dose of Cholestin (Monascus purpureus rice; red yeast rice), and 17.2% on the high dose. Lovastatin reduced severity of lesions by 89% (sudanophilia) and 84% (visual). Visual grading of lesion severity showed reduction by 38% and 68%.
TL;DR: The reduced adipose Zn concentrations in HF-fed mice and the negative correlation between serum leptin and adiposeZn concentrations support an interrelationship among obesity, leptin and Zn metabolism.
Abstract: Zinc (Zn) has been implicated in altered adipose metabolism, insulin resistance and obesity. The objective of this study was to investigate the effects dietary Zn deficiency and supplementation on adiposity, serum leptin and fatty acid composition of adipose triglycerides and phospholipid in C57BL/6J mice fed low-fat (LF) or high-fat (HF) diets for a 16 week period. Weanling C57BL/6J mice were fed LF (16% kcal from soybean oil) or HF (39% kcal from lard and 16% kcal from soybean oil) diets containing 3, 30 or 150 mg Zn/kg diet (ZD = Zn-deficient, ZC = Zn control and ZS = Zn-supplemented, respectively). HF-fed mice had higher fat pad weights and lower adipose Zn concentrations than the LF-fed mice. The ZD and ZS groups had a reduced content of fatty acids in adipose triglycerides compared to the ZC group, suggesting that zinc status may influence fatty acid accumulation in adipose tissue. Serum leptin concentration was positively correlated with body weight and body fat, and negatively correlated with adipose Zn concentration. Dietary fat, but not dietary Zn, altered the fatty acid composition of adipose tissue phospholipid and triglyceride despite differences in Zn status assessed by femur Zn concentrations. The fatty acid profile of adipose triglycerides generally reflected the diets. HF-fed mice had a higher percentage of C20:4 n-6, elevated ratio of n-6/n-3, lower ratio of PUFA/SAT and reduced percentage of total n-3 fatty acids in adipose phospholipid, a fatty acid profile associated with obesity-induced risks for insulin resistance and impaired glucose transport. In summary, the reduced adipose Zn concentrations in HF-fed mice and the negative correlation between serum leptin and adipose Zn concentrations support an interrelationship among obesity, leptin and Zn metabolism.
TL;DR: The fact that the blood cell pool reflects more intensely than plasma the changes in amino acid availability and undergoes changes according to the demand of amino acids, reinforces the important role of the cell pool in blood amino acid compartmentation and handling.
Abstract: The description of different plasma amino acid profiles for specific types of cancer suggests that the metabolic alterations brought about by each type of tumor determine their own, distinctive profile of plasma amino acids. However, the blood cell pool represents an important percentage of the total amount of amino acids and has been reported to undergo significant changes in several physiological situations, thus raising the question of what effect a situation like cancer could have on amino acid blood compartmentation. We determined the levels of individual amino acids in blood, plasma and blood cell compartment of 14 lung cancer patients, 16 breast cancer patients and the corresponding healthy controls (n = 14 and 18, respectively). Cancer, a situation of increased amino acid demand, was accompanied by a decrease in the amino acid availability, of which the blood cell pool would be the main contributor. Thus, the fact that the blood cell pool reflects more intensely than plasma the changes in amino acid availability and undergoes changes according to the demand of amino acids, reinforces the important role of the cell pool in blood amino acid compartmentation and handling. The profiles of blood amino acids characteristic of different types of tumors that have been proposed by some authors could be extended to other compartments-in addition to the plasma-and even be more informative.
TL;DR: It is suggested that the beneficial skeletal effects of genistein, at dietarily achievable levels, appear to be mediated, at least in part, by interleukin-6 and osteoprotegerin, and estrogen receptors play important roles in the inhibition of interleuko-6 synthesis bygenistein in osteoblastic MC3T3-E1 cells.
Abstract: In this in vitro study, the hypothesis that the beneficial effects of dietary genistein on bone are through the modulation of the bone marker synthesis by osteoblastic MC3T3-E1 cells was tested, and the possible roles of estrogen receptors in the actions of genistein on osteoblastic cells were also examined. Interleukin-6 production was decreased 40% to 60% in osteoblastic cells treated with genistein from either day 8-16 or day 12-16, at dietarily achievable concentrations (10(-10) to 10(-8) M) (P<0.05). The mRNA expression of osteoprotegerin increased about 140% in cells treated from with genistein day 4-8 at a concentration of 10(-8) M (P<0.05). The ratio of estrogen receptor-alpha to beta expression increased 10-fold from day 0 to 12 of culture (P<0.05). Correlating with this time-dependent variation in estrogen receptor expression, treatments of 17beta-estradiol and genistein had opposite dose patterns on the ratio of estrogen receptor-alpha to beta expression following treatment from day 4 to 6 compared to from day 0 to 2. The addition of ICI-182,780, an estrogen receptor blocker, reduced the inhibitory effect of genistein on IL-6 production by 30-50%. In summary, these findings suggest that the beneficial skeletal effects of genistein, at dietarily achievable levels, appear to be mediated, at least in part, by interleukin-6 and osteoprotegerin, and estrogen receptors play important roles in the inhibition of interleukin-6 synthesis by genistein in osteoblastic MC3T3-E1 cells.
TL;DR: It is concluded that ascorbic acid and alpha-tocopherol alleviate arsenic- induced alterations in mitochondria, and lipid peroxidation and antioxidants in liver and kidney of arsenic exposed rats.
Abstract: Arsenic exists ubiquitously in our environment and various forms of arsenic circulate in air, water, soil and living organisms. Since arsenic compounds have shown to exert their toxicity chiefly by generating reactive oxygen species, we have evaluated the effect of antioxidants ascorbic acid and alpha-tocopherol on lipid peroxidation, antioxidants and mitochondrial enzymes in liver and kidney of arsenic exposed rats. A significant increase in the level of lipid peroxidation and decrease in the levels of antioxidants and in the activities of mitochondrial enzymes were observed in arsenic intoxicated rats. Co-administration of arsenic treated rats with ascorbic acid and alpha-tocopherol showed significant reduction in the level of lipid peroxidation and elevation in the levels of ascorbic acid, alpha-tocopherol, glutathione and total sulfhydryls and in the activities of isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, NADH-dehydrogenase and cytochrome c oxidase. From our results, we conclude that ascorbic acid and alpha-tocopherol alleviate arsenic- induced alterations in mitochondria.
TL;DR: Plasma levels of antioxidant vitamins and carotenes, and also serum lipids, total cholesterol and lipoprotein-cholesterol showed an overall response to exercise, and their increase and/or decrease must be explained as a consequence of the different training status of sportsmen and intensity and duration of exercise tests.
Abstract: The aim of this work was to evaluate the effect of different intensity of exercise and different training status on antioxidants and cholesterol profile in cyclists. 33 male cyclists (17 amateur and 16 professional cyclists) participated in this study. The amateurs all trained 14 +/- 1 h each week, and their VO(2) max was 62.5 +/- 1.8 ml/Kg x min; the professionals all trained 24 +/- 1 h each week, and their VO(2) max was 80.2 +/- 1.6 ml/Kg x min. Amateurs were submitted to the maximal and submaximal prolonged exercise tests. Professionals were submitted to a mountain stage (170 km) of cycling competition. Serum lipid and cholesterol profile (triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol) and plasma antioxidant capacity (ascorbic acid, alpha-tocopherol, retinol, beta-carotene and others) were measured before and after exercise tests. Hematological determinations (number of erythrocytes, hematocrit and hemoglobin concentration) and dietary intake were also measured. No significant differences were observed in basal values (before exercise tests) of amateur and professional cyclists. Negligible differences were found between dietary intake of amateur and professional cyclists, and also the results of hematological values showed there was no effect of degree of hydration or dietary intake on blood levels of studied antioxidant and lipid parameters. An increase in plasma levels of vitamin C, vitamin E, triglycerides and VLDL-cholesterol levels, and also a decrease of beta-carotene and LDL-cholesterol. were observed in well-trained professional cyclists after the cycling stage - an endurance exercise--but not in amateur cyclists. Amateur cyclists showed only mild increases in total cholesterol after maximal and submaximal exercise, while a rise in HDL-cholesterol was only observed after maximal exercise; none of these changes were observed in professional cyclists. Plasma levels of antioxidant vitamins and carotenes, and also serum lipids, total cholesterol and lipoprotein-cholesterol showed an overall response to exercise, and their increase and/or decrease must be explained as a consequence of the different training status of sportsmen and intensity and duration of exercise tests.
TL;DR: Current research on the preventive effect of dietary vitamin B(6) against colon tumorigenesis and its possible mechanisms are described and suggested to include the suppression of cell proliferation, oxidative stress, nitric oxide synthesis, and angiogenesis.
Abstract: This review describes current research on the preventive effect of dietary vitamin B(6) against colon tumorigenesis and its possible mechanisms. Studies in cell culture have demonstrated that high levels of vitamin B(6) suppress growth of some cancer cells. From these studies it has been considered that supraphysiological doses of vitamin B(6) suppress tumor growth and metastasis. However, recent rodent study has indicated that azoxymethane-induced colon tumorigenesis in mice is suppressed by moderate doses of dietary vitamin B(6.) Epidemiological studies also support an inverse relationship between vitamin B(6) intake and colon cancer risk. Potential mechanisms underlying the preventive effect of dietary vitamin B(6) have been suggested to include the suppression of cell proliferation, oxidative stress, nitric oxide (NO) synthesis, and angiogenesis.
TL;DR: Both pre and post vitamin treatments were effective in preventing stress induced derangement of free radical metabolism with a relative dominance by latter and the combined treatment with vitamin E and C did not show any additive antioxidant effect on restraint stress induced altered freeradical metabolism.
Abstract: In the present study we examined immobilization stress-induced antioxidant defense changes in rat plasma and also observed the antioxidant effects of pre and post vitamins A, E and C administration (15 mg/Kg of body weight) individually and in combination (vit E + C) on these alterations. Following immobilization stress the circulating activities of superoxide dismutase, catalase and glutathione-S-transferase were decreased, while the level of thiobarbituric acid reactive substances (TBARS) was increased as compared to non-stressed control rats. Post treatment with individual vitamins A, E and C (after exposure to stress) resulted in a less marked alteration of plasma TBARS levels and activities of SOD, GST and catalase as compared to pre vitamin stress or stress alone treatments. Both pre and post vitamin treatments were effective in preventing stress induced derangement of free radical metabolism with a relative dominance by latter. The combined treatment with vitamin E and C did not show any additive antioxidant effect on restraint stress induced altered free radical metabolism, rather a predominant effect similar to vitamin E alone was observed. The prevention of oxidative stress generated in response to restraint stress by the vitamins can be summarized as: vitamin (E + C) i.e. vit E > vit C > vit A, thus combined vitamin (E + C) treatment though showed maximum preventive effect, but was similar to vitamin E treatment alone, in terms of the circulating activities of SOD, GST, catalase and TBARS levels.
TL;DR: This study provides the first comparative view of gene expression regulation and fully quantitative expression analysis of 35 candidate genes in a non-growing Zn deficient adult rat model and indicates the existence of individual expression pattern in liver and jejunum and their tissue specific regulation under Zn deficiency.
Abstract: In the study presented here, the effect of zinc deficiency on mRNA expression levels in liver and jejunum of adult rats was analyzed. Feed intake was restricted to 8 g/day. The semi-synthetic diet was fortified with pure phytate and contained either 2 g Zn/g (Zn deficiency, n 6) or 58 g Zn/g (control, n 7). After 29 days of Zn depletion feeding, entire jejunum and liver were retrieved and total RNA was extracted. Tissue specific expression pattern were screened and quantified by microarray analysis and verified individually via real-time RT-PCR. A relative quantification was performed with the newly developed Relative Expression Software Tool ©on numerous candidate genes which showed a differential expression. This study provides the first comparative view of gene expression regulation and fully quantitative expression analysis of 35 candidate genes in a non-growing Zn deficient adult rat model. The expression results indicate the existence of individual expression pattern in liver and jejunum and their tissue specific regulation under Zn deficiency. In addition, in jejunum a number of B-cell related genes could be demonstrated to be suppressed at Zn deficiency. In liver, metallothionein subtype 1 and 2 (MT-1 and MT-2) genes could be shown to be dramatically repressed and therefore represent putative markers for Zn deficiency. Expression results imply that some genes are expressed constitutively, whereas others are highly regulated in tissues responsible for Zn homeostasis. © 2003 Elsevier Inc. All rights reserved.
TL;DR: Data suggest that TR, known to be regulated by Se, is also upregulated as part of a host response to the dietary anticarcinogen SF, a trait not shared by another Se-dependent enzyme, GSH-Px.
Abstract: Sulforaphane (SF), a glucosinolate-derived isothiocyanate found in cruciferous vegetables, is considered an anticarcinogenic component in broccoli. Sulforaphane induces a battery of detoxification enzymes, including quinone reductase (QR). Induction is thought to be mediated through a common regulatory region termed the antioxidant response element (ARE). To test the hypothesis that the antioxidant selenoprotein thioredoxin reductase (TR) may be induced as part of this coordinated host-defense response to dietary anticarcinogenic compounds, TR activity was measured in livers of rats pair-fed diets containing SF and/or broccoli (n = 6/group). At the doses used, neither SF nor broccoli alone significantly elevated TR activity, whereas treatments containing both broccoli and SF caused a significant increase in TR activity. Glutathione peroxidase (GSH-Px), a second selenium-dependant enzyme with antioxidant activity, was downregulated in rats fed both SF and broccoli, compared to the control diet.A second experiment, using mouse hepatoma Hepa1c1c7 cells, tested whether an interaction exists between selenium (Se) and SF in TR inducibility, since Se is known to induce TR activity. Selenium (2.5 mM) plus SF (2.0 mM) caused significantly greater TR activity than either treatment alone. All treatments with added Se or SF caused significantly greater TR activities than no Se or SF treatment. Glutathione peroxidase activity was elevated by Se, but not by SF. These data suggest that TR, known to be regulated by Se, is also upregulated as part of a host response to the dietary anticarcinogen SF, a trait not shared by another Se-dependent enzyme, GSH-Px.
TL;DR: These results demonstrate that both central and excentric cleavage of lycopene occurs in the rat intestinal mucosa in the presence of soy lipoxygenase.
Abstract: Using the post-mitochondrial fraction of rat intestinal mucosa, we have investigated lycopene metabolism. The incubation media was composed of NAD + , KCl, and DTT with or without added lipoxygenase. The addition of lipoxygenase into the incubation significantly increased the production of lycopene metabolites. The enzymatic incubation products of 2 H 10 lycopene were separated using high-performance liquid chromatography and analyzed by UV/Vis spectrophotometer and atmospheric pressure chemical ionization–mass spectroscopy. We have identified two types of products: cleavage products and oxidation products. The cleavage products are likely: (1) 3-keto-apo-13-lycopenone (C 18 H 24 O 2 or 6,10,14-trimethyl-12-one-3,5,7,9,13-pentadecapentaen-2-one) with λmax = 365 nm and m/z = 272 and (2) 3,4-dehydro-5,6-dihydro-15,15′-apo-lycopenal (C 20 H 28 O or 3,7,11,15-tetramethyl-2,4,6,8,12,14-hexadecahexaen-1-al) with λmax = 380 nm and m/z = 284. The oxidative metabolites are likely: (3) 2-apo-5,8-lycopenal-furanoxide (C 37 H 50 O) with λmax = 415 nm, 435 nm, and 470 nm, and m/z = 510; (4) lycopene-5, 6, 5′, 6′-diepoxide (C 40 H 56 O 2 ) with λmax = 415 nm, 440 nm, and 470 nm, and m/z = 568; (5) lycopene-5,8-furanoxide isomer (I) (C 40 H 56 O) with λmax = 410 nm, 440nm, and 470 nm, and m/z = 552; (6) lycopene-5,8-epoxide isomer (II) (C 40 H 56 O) with λmax = 410, 440, 470 nm, and m/z = 552; and (7) 3-keto-lycopene-5′,8′-furanoxide (C 40 H 54 O 2 ) with λmax = 400 nm, 420 nm, and 450 nm, and m/z = 566. These results demonstrate that both central and excentric cleavage of lycopene occurs in the rat intestinal mucosa in the presence of soy lipoxygenase.