Isabel Corpas

Neurochemical changes in newborn rat’s brain after gestational cadmium and lead exposure

Gestational administration of cadmium (10 mg/l) and lead (300 mg/l) produced a strong decrease in proteins at birth (-17%) and on day 5 (-31%) as well as in brain lipid amount on both days (-11 and -23%, respectively). At day 5 postnatal the exposure also produced a marked decrease in DNA and RNA concentrations with respect to the control group. On the other hand, we found a significant increase of indoleamine content in all brain areas studied in the cadmium-lead group and so the dopamine and its metabolite in mesencephalon, whereas dopamine levels in metencephalon decreased significantly. This data suggests that gestational and early lactational exposure to low dose of cadmium and lead could produce alterations in monoaminergic metabolism that can place the exposed animal to a significant risk in adulthood.

Corticotropin-releasing factor stimulates metamorphosis and increases thyroid hormone concentration in prometamorphic Rana perezi larvae

Attempts to identify a hypothalamic molecule that stimulates thyrotropin (TSH) secretion from amphibian pituitary have been unsuccessful to date. The effects of mammalian (ovine and human) corticotropin-releasing factor (CRF) on the thyroid function of prometamorphic (Taylor & Kollros stages XI-XVII) (Taylor and Kollros, 1946) Rana perezi larvae were studied. Chronic treatments with both ovine and human CRF (oCRF, hCRF) stimulated metamorphosis while delaying larval growth. Chronic hCRF (1 microgram) administration induced 3.2- and 5.3-fold increases in whole body concentration of thyroxine (T4) and triiodothyronine (T3), respectively. In contrast, the 0.5-microgram dose of hCRF stimulated a significant (3.4-fold) increase in whole body concentration of T4 but not of T3. Histological studies of the thyroid gland revealed a 22% increase in the number of follicles per section as a result of the chronic treatment with oCRF (1 microgram). Acute oCRF (2 micrograms) treatment induced a significant increase in T4 concentration at 4 hr (1.3-fold) and 8 hr (2.3-fold) postinjection. T3 concentration was not altered. These results support previous reports and lead us to conclude that a CRF-like peptide, and not TRH, is involved in the regulation of thyroid activity in anuran amphibians during metamorphosis.

Gestational administration of cadmium alters the neurotransmitter levels in newborn rat brains.

The effects of gestational and early lactational intoxication by cadmium (Cd) were studied in the brain of young Wistar rats. Pregnant rats were exposed to 10 mg of cadmium acetate per litre of drinking water, from initiation of pregnancy to parturition or until postnatal day 5. At birth or on postnatal day (PND) 5 the pups were weighed, sacrificed and brains were removed and frozen for later study. Protein, lipid and nucleic acid contents were measured and the brain Cd concentration was determined. Levels of dopamine (DA), 5‐hydroxytryptamine (5‐HT) and their respective metabolites 3,4‐dihydroxyphenylacetic acid (DOPAC) and 5‐hydroxyindoleacetic acid (5‐HIAA) were measured in neonatal pup brain by higher performance liquid chromatography with electrochemical detection. The results from this experiment showed that Cd increased the 5‐HT and 5‐HIAA contents in all areas of the brain and the DA and DOPAC levels in mesencephalon, but decreased the DA and DOPAC levels in the metencephalon. On the other hand, Cd intoxication did not modify the other biochemical parameters measured, with the exception of a decrease in nucleic acids on PND 5.

Age-related changes in xanthine oxidase activity and lipid peroxidation, as well as in the correlation between both parameters, in plasma and several organs from female mice

Xanthine oxidase, a purine catabolism enzyme, has been implicated as an important source of oxidant production and plays an essential role in several inflammatory and oxidative stress-related diseases. It is known that the increasing levels of oxidants cause the chronic oxidative stress characteristic of the ageing process. The aim of the present work was to determine the changes in xanthine oxidase activity and oxidative damage to lipids in several organs (liver, kidney, spleen, lung and two different brain areas, namely cerebral cortex and brainstem) and plasma from two different age groups of BALB/c female mice: adult (7-month-old) and old (18-month-old) mice, as well as to analyse the possible correlation between both parameters. Xanthine oxidase activity was significantly increased in liver, cerebral cortex and plasma from old mice in comparison with adults. Similar results were obtained in the lipid peroxidation levels, in which old mice showed a high increment in liver and cerebral cortex. Moreover, the results show a significant and positive correlation between xanthine oxidase activity and lipid peroxidation levels in cerebral cortex. The age-related increase in the xanthine oxidase activity and lipid peroxidation in liver and cerebral cortex of mice seems to suggest that the xanthine oxidase plays a role in the acceleration of the oxidative damage in these organs with age and its possible contribution to the pathophysiological changes associated to the process of ageing.

The aged-related increase in xanthine oxidase expression and activity in several tissues from mice is not shown in long-lived animals

Xanthine oxidase (XO) is an important source of oxidant production and plays an essential role in several oxidative stress-related diseases. Aging is associated with a progressive deregulation of homeostasis as a result of a chronic oxidative stress situation. In the present work the age-related changes in XO expression and activity, as well as the activities of superoxide dismutase and catalase have been investigated in liver, kidney and thymus from four different age groups of mice, including long-lived animals. Furthermore, we have evaluated the contribution of the XO to the oxidative stress-associated with aging, in comparison to another enzymatic key source of oxidant generation, the NADPH oxidase, in peritoneal leukocytes from old mice. In all the tissues analyzed, the old mice showed higher activity and expression of XO, and decreased or unchanged superoxide dismutase and catalase activities as compared with adult mice. Moreover, the inhibition of reactive oxygen species with allopurinol or apocynin in peritoneal leukocytes from old mice, suggest that both XO and NADPH oxidase contribute to the generation of superoxide anion, whereas the XO may have a special relevance in the production of hydrogen peroxyde. Finally, long-lived animals showed a well-preserved redox state, in terms of antioxidant defenses and oxidant compounds in tissues and immune cells, which may be related to the ability of these subjects to reach a very advanced age in healthy condition. These results confirm that XO plays an important role in the age-related oxidative stress in tissues and immune cells.

Neurotoxic Effects of Gestational Administration of Low-dose Lead Acetate

Lead acetate (300 mg l−1) was administered to pregnant Wistar rats from day 1 of pregnancy to day 0 postpartum or day 5 postpartum, via drinking water. On these days, pups were sacrificed, collecting the blood to determine the concentration of lead by graphite furnace atomic absorption spectrophotometry. Brains were used to determine the total content of nucleic acids, DNA/RNA ratio and the total amount of proteins, lipids and monoamines. We found a reduction in protein content on day 0 postpartum, and changes in monoamine concentration on day 0 postpartum and day 5 postpartum. These data suggest that prenatal and early lactational exposure to a relatively low dose of lead could produce alterations in monoaminergic metabolism.

Testicular alterations in rats due to gestational and early lactational administration of lead

A solution of lead acetate (300 mg/L) was administered via drinking water to pregnant Wistar rats from day 1 of pregnancy to delivery (Pb-treated day 0 group) or throughout gestation and early lactation (from day 1 to day 5 postnatal) (Pb-treated day 5 group). When the pups were born, four dams and their offspring in each group (control day 0, Pb-treated day 0, control day 5, and Pb-treated day 5) were sacrificed on day 0 (day 0 groups) or on day 5 (day 5 groups). Relative testicular weight and gross testicular structure were not altered by the treatment. The seminiferous tubule diameter and the number of prospermatogonia were reduced by the treatment. Determination of the n-ploidy stage of prospermatogonia indicates that these cells have more proliferative activity in Pb-treated rats than in control rats. On the other hand, the total DNA, RNA, and protein content of the testes in treated rats was significantly reduced, but the DNA: RNA ratio remained unaltered.