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