We compared anxiety, neuromotor, and cognitive functions in mutant rats with different allelic variants of dopamine transporter
DAT
knockout receiving balanced or excess in fat and fructose diet. The experiments were performed in
DAT
−/− homozygotes,
DAT
+/− heterozygotes, and
DAT
+/+ wild type rats. The genotype of
DAT
‐
KO
rats was confirmed by restriction analysis of
DAT
gene compared to behavioral responses in the open field test (
OF
). Animals in the first groups of each strain were fed a balanced
AIN
93M diet; and those in the second groups with a high‐fat/high‐fructose diet. Neuromotor function was studied as grip strength, and behavioral responses were assessed in the elevated plus maze and conditioned passive avoidance response tests. The mass of the internal organs and white and brown fat, as well as selected lipid and nitrogen metabolism parameters in blood plasma were determined at the end of the experiment.
DAT
−/− had the highest specific grip strength, and showed an increase in initial exploratory activity in comparison with
DAT
+/− and DAT +/+. The exploratory activity was significantly reduced in the second test compared to the first one in
DAT
−/− and
DAT
+/− of first but not second group. Anxiety decreased with age in the second groups of
DAT
+/− and
DAT
+/+ (but not in
DAT
−/−) and was higher in
DAT
+/+ than in
DAT
+/− and
DAT
−/−. Excess fat and fructose resulted in the deterioration of short‐term memory in
DAT
+/+. Lipidomic indices of blood plasma were less responsive to diet in
DAT
−/− and
DAT
−/+ in comparison to
DAT
+/+. The increased As
AT
/Al
AT
activity ratio in
DAT
−/− compared with those in
DAT
+/+ suggests the activation of catabolism activity in the mutants. The consumption of excess fat and fructose significantly modified the effects produced by
DAT
gene allelic variants presumably due to the influence on the processes of dopamine metabolism.
Amino acids tyrosine (Tyr) and tryptophan (Trp) play a significant role in the regulation of energy metabolism, locomotor activity, and eating behavior. We studied the possibility of modulating these processes in obesity by increasing the pool of Tyr and Trp in the experimental diet. As a model of obesity, we used Wistar rats fed a diet with an excess specific energy value (HFCD) for 64 days. Trp led to a normalization of the rats’ body weight almost to the control level, but increased anxiety-like behavior and decreased long-term memory. The consumption of amino acids resulted in increased grip strength and impairment of short-term memory. The locomotor activity of animals decreased with age as a result of Tyr consumption, while Trp, on the contrary, prevented this. The Tyr supplementation led to the normalization of triglycerides and LDL. In the spleen cell lysates, amino acids suppressed the production of proinflammatory cytokines. The liver tissue morphology showed that the consumption of Tyr noticeably weakened the signs of fatty degeneration. The addition of Trp, on the contrary, led to an unfavorable effect, consisting of the appearance of a high number of large rounded fatty vacuoles. The data obtained indicate a more pronounced anti-inflammatory effect of Tyr as compared to Trp.
The experimental data on the oral toxicity of nanostructured amorphous silica (SiO2), widely used in food supplements, pharmaceuticals, and cosmetics, in terms of its in vivo effect on the immune system, are contradictory. Therefore, this study aimed to assess the rat’s immune function after SiO2 oral administration. In the first experiment, SiO2 was daily orally administered to Wistar rats for 92 days in doses of 0.1, 1.0, 10, and 100 mg/kg of body weight (bw). In the second 28-day experiment, SiO2 in a dose of 100 mg/kg bw was daily orally administered to rats parenterally immunized with the food allergen ovalbumin (OVA) for the reproduction of systemic anaphylaxis reaction. Together with integral indices, we assessed intestinal permeability to protein macromolecules; hematology; CD45RA+, CD3+, CD4+, CD8+, and CD161a+ cells; cytokines TNF-α, IL-6, and IL-10; and IgG to OVA. The results obtained showed that SiO2 has no effect on the severity of the anaphylactic reaction, but is capable inducing a toxic effect on the T-cell immune systems of rats. Estimated no observed adverse effect level NOAEL for SiO2 ranges up to 100 mg/kg bw in terms of its daily consumption for 1–3 months. Using SiO2 as a food additive should be the subject of regulation.
Behavioral indicators characterizing specific features of the pathological process of alimentary-dependent diseases were studied using in vivo model of alimentary hyperlipidemia in rats and mice. Rats and mice of the control groups received balanced semisynthetic diet for 63 days; animals of the experimental groups received a diet with high fat content (30% dry weight), balanced or high-fat diet with fructose solution instead of water, balanced cholesterol-enriched diet (0.5% dry weight), or balanced cholesterol-enriched diet with fructose solution. During the experiment, the mass of food, consumed by the animals, was monitored daily. Muscle tone was assessed by the front paw grip strength on days 33 and 54 of the experiment. Anxiety was tested in the elevated plus maze on days 36 and 57. Behavior and memory were assessed by conditioned passive avoidance reflex on days 39, 40, and 61. A significant increase in muscle tone was revealed on day 54 in rats fed with a balanced diet with fructose, and in mice, that received a similar diet, supplemented with fructose and cholesterol. Anxiety in the second test (day 57) was significantly decreased in rats fed high-fat diet and increased in mice fed high fat diet and high fat diet with fructose. In the second test, additional amount of cholesterol in the diet was the factor that significantly improved both short-term and long-term memory in both species. In mice, in contrast to rats, addition of fructose, including combination with high-fat diet, significantly worsened short-term and long-term memory. Thus, dietary factors, contributing to alimentary dyslipidemia development in rats and mice, can significantly affect the indices of neuromotor activity, anxiety level and cognitive functions, and the nature and direction of these changes are largely species-specific.
Abstract. Nanoparticles of metallic silver (Ag) are among the most widely used products of nanotechnology. Nanosized colloidal silver (NCS) is presented in many kinds of production as solutions of particles with diameter less than 100 nm. NCS is used in a variety of fields, including food supplements, medicines, cosmetics, packaging materials, disinfectants, water filters, and many others. Problems of toxicity and related safety of NCS for humans and environmental systems are recently overestimated basing on data of numerous toxicological studies in vitro and in vivo. The article discusses the results of current studies in recent years and the data of author's own experiments on studying the safety of NCS, that allows to move on to risk assessment of this nanomaterial presented in consumer products and environmental samples.
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