Effect of dietary methionine on methylmercury and atrazine toxicities

The effects of methionine (Met) on the toxicities of methylmercury (MeHg) and atrazine in male Wistar rats were investigated. Three levels of dietary Met, three levels of MeHg by gavage, and two levels of dietary atrazine were used. A two-choice form light discrimination test was used to investigate behavioral effects of the treatments. Samples of blood, liver, kidney, and brain were collected for glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd), glutathione-S-transferase (GSH-S-trans), total glutathione (GSH), prostaglandin (PG), and mercury analyses. Excess dietary Met had a protective effect on MeHg and atrazine toxicities in rats, using weight gain as the index of toxicity. Liver weight in response to the toxicants was increased in the groups of rats which were fed the lower Met levels but there was no change in those fed the highest level of Met. The highest Met level caused a lower increase in kidney weight in rats treated with MeHg. The lowest Met level caused greater mercury uptake in the organs. Atrazine caused a significant increase in mercury excretion in urine after three weeks of exposure but not at the end of the experiment, suggesting adaption. In whole blood but not in liver, GSH-Px activity declined as mercury concentration increased. Atrazine lowered liver GSH-S-trans activity. Increases in MeHg dose caused a decrease in GSH-S-trans activity in the rats fed the lowest Met level but increased it with the other diets. Treatments with MeHg caused increased synthesis of PG by platelets. Dietary Met had no effect on liver GSH but increased oxidized and total GSH in blood. Atrazine increased urinary mercapturic acid excretion. Despite clinical and biochemical effects of the treatments, the behavioral tests were negative

Caloric restriction favorably impacts metabolic and immune/inflammatory profiles in obese mice but curcumin/piperine consumption adds no further benefit

BACKGROUND: Obesity is associated with low-grade inflammation and impaired immune response. Caloric restriction (CR) has been shown to inhibit inflammatory response and enhance cell-mediated immune function. Curcumin, the bioactive phenolic component of turmeric spice, is proposed to have anti-obesity and anti-inflammation properties while piperine, another bioactive phenolic compound present in pepper spice, can enhance the bioavailability and efficacy of curcumin. This study sought to determine if curcumin could potentiate CR’s beneficial effect on immune and inflammatory responses in obesity developed in mice by feeding high-fat diet (HFD). METHODS: Mice were fed a HFD for 22 wk and then randomized into 5 groups: one group remained on HFD ad libitum and the remaining 4 groups were fed a 10% CR (reduced intake of HFD by 10% but maintaining the same levels of micronutrients) in the presence or absence of curcumin and/or piperine for 5 wk, after which CR was increased to 20% for an additional 33 wk. At the end of the study, mice were sacrificed, and spleen cells were isolated. Cells were stimulated with T cell mitogens, anti-CD3/CD28 antibodies, or lipopolysaccharide to determine T cell proliferation, cytokine production, and CD4(+) T cell subpopulations. RESULTS: Compared to HFD control group, all CR mice, regardless of the presence of curcumin and/or piperine, had lower body weight and fat mass, lower levels of blood glucose and insulin, and fewer total spleen cells but a higher percentage of CD4(+) T cells. Additionally, they demonstrated lower production of pro-inflammatory cytokines IL-1β and TNF-α, a trend toward lower IL-6, and lower production of PGE(2), a lipid molecule with pro-inflammatory and T cell-suppressive properties. Mice with CR alone had higher splenocyte proliferation and IL-2 production, but this effect of CR was diminished by spice supplementation. CR alone or in combination with spice supplementation had no effect on production of cytokines IL-4, IL-10, IFN-γ, and IL-17, or the proportion of different CD4(+) T cell subsets. CONCLUSION: CR on an HFD favorably impacts both metabolic and immune/inflammatory profiles; however, the presence of curcumin and/or piperine does not amplify CR’s beneficial effects

Modulation of cAMP levels by highâ fat diet and curcumin and regulatory effects on CD36/FAT scavenger receptor/fatty acids transporter gene expression

Curcumin, a polyphenol from turmeric (Curcuma longa), reduces inflammation, atherosclerosis, and obesity in several animal studies. In Ldlrâ /â mice fed a highâ fat diet (HFD), curcumin reduces plasma lipid levels, therefore contributing to a lower accumulation of lipids and to reduced expression of fatty acid transport proteins (CD36/FAT, FABP4/aP2) in peritoneal macrophages. In this study, we analyzed the molecular mechanisms by which curcumin (500, 1000, 1500 mg/kg diet, for 4 months) may influence plasma and tissue lipid levels in Ldlrâ /â mice fed an HFD. In liver, HFD significantly suppressed cAMP levels, and curcumin restored almost normal levels. Similar trends were observed in adipose tissues, but not in brain, skeletal muscle, spleen, and kidney. Treatment with curcumin increased phosphorylation of CREB in liver, what may play a role in regulatory effects of curcumin in lipid homeostasis. In cell lines, curcumin increased the level of cAMP, activated the transcription factor CREB and the human CD36 promoter via a sequence containing a consensus CREB response element. Regulatory effects of HFD and Cur on gene expression were observed in liver, less in skeletal muscle and not in brain. Since the cAMP/protein kinase A (PKA)/CREB pathway plays an important role in lipid homeostasis, energy expenditure, and thermogenesis by increasing lipolysis and fatty acid βâ oxidation, an increase in cAMP levels induced by curcumin may contribute to its hypolipidemic and antiâ atherosclerotic effects. © 2016 BioFactors, 43(1):42â 53, 2017Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136289/1/biof1307_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136289/2/biof1307.pd

Effect of dietary methionine on methylmercury and atrazine toxicities

The effects of methionine (Met) on the toxicities of methylmercury (MeHg) and atrazine in male Wistar rats were investigated. Three levels of dietary Met, three levels of MeHg by gavage, and two levels of dietary atrazine were used. A two-choice form light discrimination test was used to investigate behavioral effects of the treatments. Samples of blood, liver, kidney, and brain were collected for glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd), glutathione-S-transferase (GSH-S-trans), total glutathione (GSH), prostaglandin (PG), and mercury analyses. Excess dietary Met had a protective effect on MeHg and atrazine toxicities in rats, using weight gain as the index of toxicity. Liver weight in response to the toxicants was increased in the groups of rats which were fed the lower Met levels but there was no change in those fed the highest level of Met. The highest Met level caused a lower increase in kidney weight in rats treated with MeHg. The lowest Met level caused greater mercury uptake in the organs. Atrazine caused a significant increase in mercury excretion in urine after three weeks of exposure but not at the end of the experiment, suggesting adaption. In whole blood but not in liver, GSH-Px activity declined as mercury concentration increased. Atrazine lowered liver GSH-S-trans activity. Increases in MeHg dose caused a decrease in GSH-S-trans activity in the rats fed the lowest Met level but increased it with the other diets. Treatments with MeHg caused increased synthesis of PG by platelets. Dietary Met had no effect on liver GSH but increased oxidized and total GSH in blood. Atrazine increased urinary mercapturic acid excretion. Despite clinical and biochemical effects of the treatments, the behavioral tests were negative.</p

The rise, the fall and the renaissance of vitamin E

This review deals with the expectations of vitamin E ability of preventing or curing, as a potent antioxidant, alleged oxidative stress based ailments including cardiovascular disease, cancer, neurodegenerative diseases, cataracts, macular degeneration and more. The results obtained with clinical intervention studies have highly restricted the range of effectiveness of this vitamin. At the same time, new non-antioxidant mechanisms have been proposed. The new functions of vitamin E have been shown to affect cell signal transduction and gene expression, both in vitro and in vivo. Phosphorylation of vitamin E, which takes place in vivo, results in a molecule provided with functions that are in part stronger and in part different from those of the non-phosphorylate compound. The in vivo documented functions of vitamin E preventing the vitamin E deficiency ataxia (AVED), slowing down the progression of non-alcoholic steato-hepatitis (NASH), decreasing inflammation and potentiating the immune response are apparently based on these new molecular mechanisms. It should be stressed however that vitamin E, when present at higher concentrations in the body, should exert antioxidant properties to the extent that its chromanol ring is unprotected or un-esterified

α‐Tocopheryl Phosphate Induces VEGF Expression via CD36/PI3Kγ in THP‐1 Monocytes

ABSTRACT The CD36 scavenger receptor binds several ligands and mediates ligand uptake and ligand‐dependent signal transduction and gene expression, events that may involve CD36 internalization. Here we show that CD36 internalization in THP‐1 monocytes is triggered by α‐tocopherol (αT) and more strongly by α‐tocopheryl phosphate (αTP) and EPC‐K1, a phosphate diester of αTP and L‐ascorbic acid. αTP‐triggered CD36 internalization is prevented by the specific covalent inhibitor of selective lipid transport by CD36, sulfo‐N‐succinimidyl oleate (SSO). Moreover, SSO inhibited the CD36‐mediated uptake of 14C‐labelled αTP suggesting that αTP binding and internalization of CD36 is involved in cellular αTP uptake, whereas the uptake of αT was less affected. Similar to that, inhibition of selective lipid transport of the SR‐BI scavenger receptor resulted mainly in reduction of αTP and not αT uptake. In contrast, uptake of αT was mainly inhibited by Dynasore, an inhibitor of clathrin‐mediated endocytosis, suggesting that the differential regulatory effects of αTP and αT on signaling may be influenced by their different routes of uptake. Interestingly, αTP and EPC‐K1 also reduced the neutral lipid content of THP‐1 cells and the phagocytosis of fluorescent Staphylococcus aureus bioparticles. Moreover, induction of the vascular endothelial growth factor (VEGF) promoter activity by αTP occurred via CD36/PI3Kγ/Akt, as it could be inhibited by specific inhibitors of this pathway (SSO, Wortmannin, AS‐605240). These results suggest that αTP activates PI3Kγ/Akt signaling leading to VEGF expression in monocytes after binding to and/or transport by CD36, a receptor known to modulate angiogenesis in response to amyloid beta, oxLDL, and thrombospondin. J. Cell. Biochem. 118: 1855–1867, 2017. © 2017 Wiley Periodicals, Inc. In this study we characterize the molecular mechanisms and cellular consequences that are associated with the internalization of the CD36 scavenger receptors induced by vitamin E analogs. In particular, we observe the reduction of bacterial phagocytosis and lipid accumulation and the induction of the PI3Kgamma/Akt signal transduction leading to the stimulation of VEGF expression

Induction of VEGF Expression by Alpha-Tocopherol and Alpha-Tocopheryl Phosphate via PI3K gamma/PKB and hTAP1/SEC14L2-Mediated Lipid Exchange

In several studies, vitamin E has been observed to influence angiogenesis and vasculogenesis. We recently showed that the phosphorylated form of alpha-tocopherol (alpha T), alpha-tocopheryl phosphate (alpha TP), increases the expression of the vascular endothelial growth factor (VEGF). Thus, alpha TP may act as an active lipid mediator increasing VEGF expression, angiogenesis, and vasculogenesis. Here, we investigated the molecular signaling mechanisms by which alpha TP induces VEGF expression using cultured HEK293 cells as model system. alpha T and more so alpha TP increased VEGF-promoter activity in a phosphatidylinositol-3-kinase gamma (PI3K gamma)-dependent manner. In contrast, after overexpression of PI3K gamma and/or protein kinase B (PKB), VEGF promoter activity was inhibited by alpha T and more so by alpha TP. Inhibition by alpha T and alpha TP was dependent on the lipid kinase activity of PI3K gamma, whereas an induction was seen with the protein kinase activity, consistent with a model in which PKB inhibition by alpha T or alpha TP occurs only when activated at the plasma membrane and possibly involves a phosphatase such as PHLPP1. PI3K gamma-induced VEGF expression was reduced when the human tocopherol-associated protein 1 (hTAP1/SEC14L2) was overexpressed suggesting formation of an inactive PI3K gamma/hTAP1 heterodimer, that could be reactivated by alpha T and more so by alpha TP. We suggest a novel signaling mechanism by which alpha TP stimulates PI3K gamma activity by stimulating hTAP-mediated phosphatidylinositol exchange and presentation to the enzyme and/or dissociation of an inactive heterodimer. At cellular level, hTAP may act as sensor for intracellular lipid information (location, type, and amount of lipid) and translate it into responses of PI3K-mediated signaling and gene expression. (C) 2014 Wiley Periodicals, Inc