Toxicity of thimerosal in biological systems: Conformational changes in human hemoglobin, decrease of oxygen binding capacity, increase of protein glycation and amyloid's formation.

Thimerosal (TH), an organomercurial compound, is used as a preservative in vaccines and cosmetics. Its interaction with human hemoglobin (Hb) was investigated under physiological conditions using biophysical and biological assays, aiming to evaluate hazardous effects. TH interacts spontaneously with Hb (stoichiometry 2:1, ligand-protein), preferably by electrostatic forces, with a binding constant of 1.41 × 106 M-1. Spectroscopic data allows to proposing that TH induces structural changes in Hg, through ethylmercury transfer to human Hb-Cys93 residues, forming thiosalicylic acid, which, in turn, interacts with the positive side of the amino acid in the Hb-HgEt adduct chain. As a consequence, inhibition of Hb-O2 binding capacity up to 72% (human Hb), and 50% (human erythrocytes), was verified. Dose-dependent induction of TH forming advanced glycation end products (AGE) and protein aggregates (amyloids) was additionally observed. Finally, these results highlight the toxic potential of the use of TH in biological systems, with a consequent risk to human health.

Neonatal fluoxetine exposure modulates serotonergic neurotransmission and disturb inhibitory action of serotonin on food intake.

The neurotransmitter serotonin (5-HT) acts as an important regulator of the critical neurodevelopmental processes and thus alterations in 5-HT signaling early promotes permanent structural and functional changes in brain. The selective serotonin reuptake inhibitors (SSRIs), as fluoxetine and citalopram, blocking serotonin transporter (SERT) at the presynaptic neuron, which regulates extracellular 5-HT levels. Evidence suggests that the exposure to SSRIs in the neurodevelopmental period may alters 5-HT signaling sensitivity on food intake control. The aim of the present study was to evaluate the effects of neonatal exposure to fluoxetine on molecular and cellular components of the serotonergic system and food intake control in young animals. Methods: The animals were divided according to experimental manipulation, Fluoxetine Group (FG): male pups received application of fluoxetine (10 mg/kg, 10 µL/g) and Saline Group (SG): male pups received saline application (0.9% NaCl, 10 µL/g), both throughout lactation (PND1-PND21). They evaluated body weight, food intake, SERT gene and protein expression, serotonin content in the hypothalamus. The neonatal exposure to fluoxetine promoted reduction in body weight, disturb the serotonin hypophagic response, and increase the serotonin and SERT hypothalamic in young animals. We conclude that the changes of components of the serotonergic system by neonatal exposure to fluoxetine may be responsible for disturb the inhibitory action of serotonin on food intake.

Mitochondrial bioenergetics and oxidative status disruption in brainstem of weaned rats: Immediate response to maternal protein restriction.

Mitochondrial bioenergetics dysfunction has been postulated as an important mechanism associated to a number of cardiovascular diseases in adulthood. One of the hypotheses is that this is caused by the metabolic challenge generated by the mismatch between prenatal predicted and postnatal reality. Perinatal low-protein diet produces several effects that are manifested in the adult animal, including altered sympathetic tone, increased arterial blood pressure and oxidative stress in the brainstem. The majority of the studies related to nutritional programming postulates that the increased risk levels for non-communicable diseases are associated with the incompatibility between prenatal and postnatal environment. However, little is known about the immediate effects of maternal protein restriction on the offspring's brainstem. The present study aimed to test the hypothesis that a maternal low-protein diet causes tissue damage immediately after exposure to the nutritional insult that can be assessed in the brainstem of weaned offspring. In this regard, a series of assays was conducted to measure the mitochondrial bioenergetics and oxidative stress biomarkers in the brainstem, which is the brain structure responsible for the autonomic cardiovascular control. Pregnant Wistar rats were fed ad libitum with normoprotein (NP; 17% casein) or low-protein (LP; 8% casein) diet throughout pregnancy and lactation periods. At weaning, the male offsprings were euthanized and the brainstem was quickly removed to assess the mitochondria function, reactive oxygen species (ROS) production, mitochondrial membrane electric potential (ΔΨm), oxidative biomarkers, antioxidant defense and redox status. Our data demonstrated that perinatal LP diet induces an immediate mitochondrial dysfunction. Furthermore, the protein restriction induced a marked increase in ROS production, with a decrease in antioxidant defense and redox status. Altogether, our findings suggest that LP-fed animals may be at a higher risk for oxidative metabolism impairment throughout life than NP-fed rats, due to the immediate disruption of the mitochondrial bioenergetics and oxidative status caused by the LP diet.