Thallium-induced DNA damage, genetic, and epigenetic alterations

Thallium (Tl) is a toxic heavy metal responsible for noxious effects in living organisms. As a pollutant, Tl can be found in the environment at high concentrations, especially in industrial areas. Systemic toxicity induced by this toxic metal can affect cell metabolism, including redox alterations, mitochondrial dysfunction, and activation of apoptotic signaling pathways. Recent focus on Tl toxicity has been devoted to the characterization of its effects at the nuclear level, with emphasis on DNA, which, in turn, may be responsible for cytogenetic damage, mutations, and epigenetic changes. In this work, we review and discuss past and recent evidence on the toxic effects of Tl at the systemic level and its effects on DNA. We also address Tl’s role in cancer and its control

Prenatal Stress Reduces Learning and Memory in Pre-pubertal, Young, and Adult Rats of Both Sexes

Prenatal stress (PS) induced by immobilization produces defi ciencies in spatial learning and information retrieval. These defi ciencies seem to be larger in males than in females, and have been explained as an effect of fetal exposure to high concentrations of maternal corticosterone during stress response. However, the effects of PS have only been assessed at a single time point and/or sex. In this work, the effect of PS on spatial learning and memory induced by immersion in cold water was evaluated in young and adult rats of both sexes. PS was induced during gestational days 15 through 21. Corticosterone in dams, body weight, corticosterone, learning and memory were assessed in male and female offspring at one, two, and three months of postnatal life. Results showed that escape latencies of PS rats of both sexes were longer as compared to those of control groups and that the number of platformsite crossovers and time spent in the platform quadrant were lower in the PS animals as compared to the control groups. Corticosterone levels were higher in PS females and males compared with controls. The body weight was decreased only in PS males of one month of age. These results show that PS by immersion in cold water alters learning and memory processes in the offspring, regardless of sex or age, since the effects are similar in females and males during youth and adulthood. These behavioral effects are related to high serum corticosterone.</p

Compounds from Ilex paraguariensis extracts confer antioxidant effects in the brains of rats subjected to chronic immobilization stress

Immobilization induces oxidative damage to the brain. Ilex paraguariensis extracts (Mate) and chlorogenic acid (CGA), its major natural compound, exert protective effects against reactive oxygen species (ROS) formation. Here, the effects of Mate and CGA on oxidative damage induced by chronic immobilization stress (CIS) in cortex (CTX), hippocampus (HIP) and striatum (STR) were investigated. For CIS, animals were immobilized during 6 h every day for 21 consecutive days. Rats received Mate or CGA daily by intra-gastric gavage 30 min before every restraint session. Endpoints of oxidative stress (levels of lipid peroxidation, protein carbonylation, and reduced (GSH) and oxidized (GSSG) forms of glutathione) were evaluated following CIS. While CIS increased oxidized lipids and carbonyl levels in all brain regions, CGA (and Mate in a lesser extent) attenuated lipid and protein oxidation as compared to control groups. GSH/GSSG balance showed a tendency to increase in all regions in response to stress and antioxidants. Taken together, our results support a protective role of dietary antioxidants against the neuronal consequences of stress.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Comparing the Neuroprotective Effects of Caffeic Acid in Rat Cortical Slices and Caenorhabditis elegans: Involvement of Nrf2 and SKN-1 Signaling Pathways.

Caffeic acid (CA) is a hydroxycinnamic acid derivative and polyphenol with antioxidant and anti-inflammatory activities. The neuroprotective properties of CA still need detailed characterization in different biological models. Here, the antioxidant and neuroprotective effects of CA were compared in in vitro and in vivo neurotoxic models. Biochemical outcomes of cell dysfunction, oxidative damage, and transcriptional regulation were assessed in rat cortical slices, whereas endpoints of physiological stress and motor alterations were characterized in Caenorhabditis elegans (C. elegans). In rat cortical slices, CA (100 μM) prevented, in a differential manner, the loss of reductive capacity, the cell damage, and the oxidative damage induced by the excitotoxin quinolinic acid (QUIN, 100 μM), the pro-oxidant ferrous sulfate (FeSO4, 25 μM), and the dopaminergic toxin 6-hydroxydopamine (6-OHDA, 100 μM). CA also restored the levels of nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE; a master antioxidant regulatory pathway) binding activity affected by the three toxins. In wild-type (N2) of C. elegans, but not in the skn-1 KO mutant strain (worms lacking the orthologue of mammalian Nrf2), CA (25 mM) attenuated the loss of survival induced by QUIN (100 mM), FeSO4 (15 mM), and 6-OHDA (25 mM). Motor alterations induced by the three toxic models in N2 and skn-1 KO strains were prevented by CA in a differential manner. Our results suggest that (1) CA affords partial protection against different toxic insults in mammalian brain tissue and in C. elegans specimens; (2) the Nrf2/ARE binding activity participates in the protective mechanisms evoked by CA in the mammalian cortical tissue; (3) the presence of the orthologous skn-1 pathway is required in the worms for CA to exert protective effects; and (4) CA exerts antioxidant and neuroprotective effects through homologous mechanisms in different species