Basal Intestinal Morphology, Immunolocalization of Leptin and Ghrelin and Their Receptors in Newborn Wistar Rats after Prenatal Exposure to Fumonisins.

Animal feed is very frequently contaminated with different types of mold, the metabolites of which are toxic to living organisms. Mold-contaminated cereal is rich in heat-resistant and harmful metabolites such as fumonisins (FBs). The amount of FBs consumed as part of animal feed, including livestock feed, is unknown. Therefore, this study aimed to evaluate the effects of maternal oral FB intoxication on basal duodenum morphology and the immunolocalization of gut hormones responsible for food intake (leptin and ghrelin), as well as their receptors, in newborn rat offspring. Pregnant Wistar rats were randomly allocated to one of three groups: a control group or one of two FB-intoxicated groups (60 or 90 mg FB/kg b.w., respectively). Basal morphological duodenal parameters changed in a dose- and sex-dependent manner. The intensity of the ghrelin immunoreaction was unchanged in females, while in males it increased after FB exposure (60 mg/kg b.w.), with a simultaneous decrease in expression of the ghrelin receptor. Leptin and its receptor immunoreaction intensity was decreased in both sexes following FB exposure. The current study highlighted the potential involvement of intestinal ghrelin and leptin in the metabolic disturbances observed later in life in offspring that were prenatally exposed to fumonisins.

The Effects of Prenatal Supplementation with ß-Hydroxy-ß-Methylbutyrate and/or Alpha-Ketoglutaric Acid on the Development and Maturation of Mink Intestines Are Dependent on the Number of Pregnancies and the Sex of the Offspring.

Prenatal and postnatal supplementation with ß-hydroxy-ß-methylbutyrate (HMB) and alpha-ketoglutaric acid (AKG) affects the development and maturation of offspring. Both substances have the potential to stimulate cell metabolism via different routes. However, parity affects development and may alter the effects of dietary supplementation. This study aimed to evaluate the effect of gestational supplementation with HMB and/or AKG to primiparous and multiparous minks on the structure and maturation of the offspring's small intestine. Primiparous and multiparous American minks (Neovison vison), of the standard dark brown type, were supplemented daily with HMB (0.02 g/kg b.w.) and/or AKG (0.4 g/kg b.w.) during gestation (n = 7 for each treatment). Supplementation stopped when the minks gave birth. Intestine samples were collected from 8-month-old male and female offspring during autopsy and histology and histomorphometry analysis was conducted (LAEC approval no 64/2015). Gestational supplementation had a long-term effect, improving the structure of the offspring's intestine toward facilitating absorption and passage of intestinal contents. AKG supplementation affected intestinal absorption (enterocytes, villi and absorptive surface), and HMB affected intestinal peristalsis and secretion (crypts and Goblet cells). These effects were strongly dependent on parity and offspring gender. Present findings have important nutritional implications and should be considered in feeding practices and supplementation plans in animal reproduction.

The Protective Role of Alpha-Ketoglutaric Acid on the Growth and Bone Development of Experimentally Induced Perinatal Growth-Retarded Piglets.

The effect of alpha-ketoglutaric acid (AKG) supplementation to experimentally-induced, perinatal growth-retarded piglets was examined. Sows were treated with a synthetic glucocorticoid (Gc) during the last 25 days of pregnancy, and after the birth, piglets were randomly divided into three groups depending on the treatment. The Gc/Gc + AKG and Gc/AKG groups born by Gc-treated sows after the birth were treated with Gc or Gc + AKG for 35 days. Significantly lower serum growth hormone, IGF-I, osteocalcin, leptin, and cortisol concentrations were observed in the Gc/Gc + AKG group, while the bone alkaline phosphatase activity was significantly higher. Serum insulin concentration was higher in the control group. Serum alanine, lysine, histidine, and tryptophan concentrations were higher in the Gc/Gc + AKG and Gc/AKG groups. The perinatal action of Gc significantly affects histomorphometry of articular cartilage and trabecular bone and bone mechanics. The results clearly showed that dietary AKG had positive effects with regards to the profile of free amino acids. Taking into account the function of AKG as an energy donor and stimulator of collagen synthesis, it can be concluded that the anabolic role of AKG may be the main mechanism responsible for its protective effect against the GC-induced perinatal intensified catabolic state.

Near-Surface Studies of the Changes to the Structure and Mechanical Properties of Human Enamel under the Action of Fluoride Varnish Containing CPP-ACP Compound.

Changes to the features of the enamel surface submitted to induced demineralisation and subsequent remineralisation were studied. The in vitro examination was conducted on polished slices of human molar teeth, divided in four groups: the untreated control (n = 20), challenged by a demineralisation with orthophosphoric acid (H3PO4) (n = 20), and challenged by a demineralisation following remineralisation with fluoride (F) varnish containing casein phosphopeptides (CPP) and amorphous calcium phosphate (ACP) compounds (n = 20). The specimens' enamel surfaces were subjected to analysis of structure, molecular arrangement, mechanical features, chemical composition, and crystalline organization of apatite crystals. Specimens treated with acid showed a significant decrease in crystallinity, calcium, and phosphorus levels as well as mechanical parameters, with an increase in enamel surface roughness and degree of carbonates when compared to the control group. Treatment with fluoride CPP-ACP varnish provided great improvements in enamel arrangement, as the destroyed hydroxyapatite structure was largely rebuilt and the resulting enamel surface was characterised by greater regularity, higher molecular and structural organisation, and a smoother surface compared to the demineralised one. In conclusion, this in vitro study showed that fluoride CPP-ACP varnish, by improving enamel hardness and initiating the deposition of a new crystal layer, can be an effective remineralising agent for the treatment of damaged enamel.

Chronic dietary supplementation with kynurenic acid, a neuroactive metabolite of tryptophan, decreased body weight without negative influence on densitometry and mandibular bone biomechanical endurance in young rats.

Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan. KYNA naturally occurs in breast milk and its content increases with lactation, indicating the role of neonatal nutrition in general growth with long-term health effects. KYNA is also an antagonist of ionotropic glutamate receptors expressed in bone cells. The aim of this study was to establish the effects of chronic KYNA supplementation on bone homeostasis in young rats, using mandible as a model bone. Female and male newborn Wistar rats were divided into control and KYNA-administered groups until 60 days of age (25x101 mg/L or 25x102 mg/L in drinking water). Hemimandibles were subjected to densitometry, computed tomography analysis and mechanical testing. Rats supplemented with KYNA at both doses showed a decrease in body weight. There were no effects of KYNA administration and mandible histomorphometry. In males, a significant quadratic effect (P < 0.001) was observed in the densitometry of the hemimandible, where BMD increased in the group supplemented with 2.5x101 mg/L of KYNA. Analysis of mechanical tests data showed that when fracture forces were corrected for bone geometry and rats body weight the improvement of bone material properties was observed in male and female rats supplemented with lower dose of KYNA. This study showed that chronic supplementation with KYNA may limit weight gain in the young, without adversely affecting the development of the skeleton.

Surface analysis of etched enamel modified during the prenatal period.

Structural changes in the enamel surface subjected to induced demineralization and assessment of the influence of prenatal administration of ß-hydroxy ß-methylbutyrate (HMB) on enamel resistance were investigated. The examination was conducted on five sets of teeth from one-day-old spiny mice (Acomys cahirinus), one from the control and four from the experimental groups. Surface structure, molecular arrangement and crystalline organization of offspring's enamel both before and after etching were studied. Obtained results revealed that the physical and molecular arrangements of enamel were altered after the prenatal supplementation, and significantly affected its final structure and resistance against acid action. The enamel of incisors from the offspring which mothers were supplemented with HMB in a high dose (0.2 g/kgbw) and in the late period of gestation (26th-39th day) showed the highest endurance against acid treatment demonstrating only vestigial changes in their surface structure after acid action. Comparing to the remaining experimental groups, it was characterized by a reduced roughness and fractal dimension, significantly lower degree of demineralization and simultaneous lack of notable differences in the Raman spectra before and after acid etching. The results suggest that an increased enamel resiliency was the effect of a relatively high degree of mineralization and higher organization of the surface.

Long-term exposure to nicotine markedly reduces kynurenic acid in rat brain--in vitro and ex vivo evidence.

Kynurenic acid (KYNA) is a recognized broad-spectrum antagonist of excitatory amino acid receptors with a particularly high affinity for the glycine co-agonist site of the N-methyl-D-aspartate (NMDA) receptor complex. KYNA is also a putative endogenous neuroprotectant. Recent studies show that KYNA strongly blocks alpha7 subtype of nicotinic acetylcholine receptors (nAChRs). The present studies were aimed at assessing effects of acute and chronic nicotine exposure on KYNA production in rat brain slices in vitro and ex vivo. In brain slices, nicotine significantly increased KYNA formation at 10 mM but not at 1 or 5 mM. Different nAChR antagonists (dihydro-beta-erythroidine, methyllycaconitine and mecamylamine) failed to block the influence exerted by nicotine on KYNA synthesis in cortical slices in vitro. Effects of acute (1 mg/kg, i.p.), subchronic (10-day) and chronic (30-day) administration of nicotine in drinking water (100 microg/ml) on KYNA brain content were evaluated ex vivo. Acute treatment with nicotine (1 mg/kg i.p.) did not affect KYNA level in rat brain. The subchronic exposure to nicotine in drinking water significantly increased KYNA by 43%, while chronic exposure to nicotine resulted in a reduction in KYNA by 47%. Co-administration of mecamylamine with nicotine in drinking water for 30 days reversed the effect exerted by nicotine on KYNA concentration in the cerebral cortex. The present results provide evidence for the hypothesis of reciprocal interaction between the nicotinic cholinergic system and the kynurenine pathway in the brain.

Presence of kynurenic acid in food and honeybee products.

Kynurenic acid (KYNA) is an endogenous antagonist of ionotropic glutamate receptors and the alpha 7 nicotinic acetylcholine receptor, showing anticonvulsant and neuroprotective activity. In this study, the presence of KYNA in food and honeybee products was investigated. KYNA was found in all 37 tested samples of food and honeybee products. The highest concentration of KYNA was obtained from honeybee products' samples, propolis (9.6 nmol/g), honey (1.0-4.8 nmol/g) and bee pollen (3.4 nmol/g). A high concentration was detected in fresh broccoli (2.2 nmol/g) and potato (0.7 nmol/g). Only traces of KYNA were found in some commercial baby products. KYNA administered intragastrically in rats was absorbed from the intestine into the blood stream and transported to the liver and to the kidney. In conclusion, we provide evidence that KYNA is a constituent of food and that it can be easily absorbed from the digestive system.

Kynurenic acid in human saliva--does it influence oral microflora?

Kynurenic acid (KYNA) is an endogenous antagonist of alpha7 nicotinic receptors and all ionotropic glutamate receptors. Its neuroprotective activity has been suggested. In this study, the presence of KYNAin human saliva and its potential bactericidal role was investigated. KYNAwas found in all samples of human saliva with mean concentration of 3.4 nM. The concentration of KYNA in saliva obtained from patients with odontogenic abscesses was 3.5 times higher than in healthy subjects. We have shown that the human gingival fibroblasts produce KYNAand an inflammatory stimulant, lipopolysaccharide, enhanced its synthesis in vitro. The bactericidal effect of KYNA was also presented. We hypothesize that KYNA may contribute to the control of oral microflora.

Effect of pesticides on kynurenic acid production in rat brain slices.

Kynurenic acid (KYNA) is a broad spectrum antagonist of ionotropic glutamate receptors, preferentially active at the strychnine-insensitive glycine allosteric site of the N-methyl-D-aspartate (NMDA) receptor, and a noncompetitive antagonist of alpha7 nicotinic receptor. Animal studies showed that it possesses anticonvulsant and neuroprotective properties. Its involvement in the pathophysiology of various brain disorders was suggested. In this study, the effect of pesticides on KYNA production in brain cortical slices was investigated. Pyrethroids, deltamethrin and fenpropathrin significantly lowered KYNA production. Methomyl, bensultap, fipronil, diquat and MCPA were ineffective in this regard. In view of this data, the inhibition of KYNA synthesis appear to merit further investigation as a potential factor contributing to the toxicology of pyrethroids.