The intertwining between lead and ethanol in the model organism Caenorhabditis elegans.

Caenorhabditis elegans (C. elegans) is a model organism widely used to evaluate the mechanistic aspects of toxicants with the potential to predict responses comparable to those of mammals. We report here the consequences of developmental lead (Pb) exposure on behavioral responses to ethanol (EtOH) in C. elegans. In addition, we present data on morphological alterations in the dopamine (DA) synapse and DA-dependent behaviors aimed to dissect the neurobiological mechanisms that underlie the relationship between these neurotoxicants. Finally, the escalation to superior animals that parallels the observed effects in both experimental models with references to EtOH metabolism and oxidative stress is also discussed. Overall, the literature revised here underpins the usefulness of C. elegans to evidence behavioral responses to a combination of neurotoxicants in mechanistic-orientated studies.

Nivel de exposición al plomo en niños y su correlación con indicadores de stres oxidativo / Level of exposure to lead in children and its correlation with indicators of oxidative stress

INTRODUCCIÓN El plomo (Pb) es un metal neurotóxico particularmente en organismos en desarrollo. Uno de los mecanismos de acción propuestos con implicancias diagnósticas y terapéuticas es su capacidad de inducir estrés oxidativo. OBJETIVOS Determinar la plombemia en niños expuestos ambientalmente al Pb y establecer su relación con factores de riesgo de exposición y con marcadores de lesión bioquímica (actividad de enzimas antioxidantes: catalasa, glutatión peroxidasa, superóxido dismutasa, y grado de peroxidación lipídica TBARS). MÉTODOS Se realizó un estudio analítico de corte transversal. Se evaluaron niños de 1 a 6 años asistidos en el sistema público de salud. Se determinaron plombemias por espectrofotometría de absorción atómica y actividades de las enzimas antioxidantes y TBARS por técnicas espectrofotométricas. Los factores de riesgo se relevaron mediante una encuesta. Se utilizaron los tests de Mann Whitney (MW) o Kruskal Wallis (KW) para comparar los niveles de plomo (transformados a logaritmo natural) entre los grupos de niños con y sin presencia de los factores de riesgo considerados y para comparar los niveles de enzimas y TBARS entre niveles de plomo mayores o menores al límite de cuantificación (2,7 µg/dL). Se utilizó el test de Spearman para evaluar la correlación entre los niveles de plomo y de los indicadores de estrés oxidativa. RESULTADOS Participaron 134 niños. La media geométrica (MG) del plomo fue de 1,73 µg/dL (IC 95% 1,51-1,99). El 31% tenían niveles cuantificables de plomo y sólo el 3% niveles ≥5 µg/dL. Se encontró correlación significativa entre los niveles de plomo y los TBARS (p=0,034), no así con las actividades enzimáticas. DISCUSIÓN Los niveles de plomo en sangre hallados en los niños de 1 a 6 años sugieren un nivel bajo de exposición ambiental al metal. Si bien estos niveles de exposición no inducen alteraciones en la actividad de enzimas antioxidantes, sí evidencian daño en membranas celulares por peroxidación lipídica.

Blood lead levels and enzymatic biomarkers of environmental lead exposure in children in Cordoba, Argentina, after the ban of leaded gasoline.

Lead (Pb) is a developmental neurotoxicant found in industrial activities, many of them already prohibited worldwide. This study aimed to evaluate current blood Pb (PbB) levels in children in Cordoba, Argentina, and to compare these with similar studies performed before Pb was banned in gasoline in 1996. We also sought to identify mechanistically relevant biomarkers by measuring δ-aminolevulinic acid dehydratase (δ-ALAD), superoxide dismutase (SOD), and catalase (CAT) activities. We finally aimed to determine whether sociodemographic characteristics are associated with Pb toxicity. Blood samples collected from 161 healthy children between September 2009 and February 2010 revealed mean PbB levels of 2.58 ± 0.30 µg/dl. Enzymatic δ-ALAD, CAT, and SOD activities showed no significant variations when plotted against PbB levels. Finally, children living in the suburbs have higher PbB levels than their city counterparts, while low socioeconomic status increased δ-ALAD inhibition compared with that of middle-income children. Overall, these results evidenced a substantial reduction in exposure to Pb in this pediatric population over a decade after Pb was restricted in gasoline and reveal the importance of pursuing novel biomarkers of toxicity along with the sociodemographic profile to complement Pb diagnosis.

Reduction in hospital admissions for acute coronary syndrome after the successful implementation of 100% smoke-free legislation in Argentina: a comparison with partial smoking restrictions.

BACKGROUND: Several studies have shown a decrease in acute coronary syndrome (ACS) admissions after the implementation of 100% smoke-free legislation. However, no studies have been conducted in developing countries. METHODS: We conducted a time series analysis of ACS hospital admissions in Santa Fe province and Buenos Aires city, Argentina. In 2006, Santa Fe implemented a 100% smoke-free law and Buenos Aires implemented a partial law with designated smoking areas and exceptions. Age-standardised ACS admissions rates were compared before and after the implementation of the laws in each district. Smoking prevalence, compliance with legislation and exposure to secondhand smoke (SHS) was also assessed in both districts. RESULTS: In Santa Fe an immediate decrease in ACS admissions was observed after implementation (-2.5 admissions per 100,000, p=0.03; 13% reduction), compared with no change in Buenos Aires city (rate ratio Santa Fe vs Buenos Aires: 0.74, 95% CI 0.63 to 0.86, p≤0.001). In Santa Fe, the immediate effect was followed by a persistent decrease in admissions due to ACS (-0.26 admissions per 100,000 per month). Smoking prevalence did not change significantly in either district during the same period. In both districts, there was a reduction in self-reported SHS exposure, with a trend towards lower exposure in Santa Fe province. No other comprehensive tobacco control interventions were implemented during the study period. CONCLUSIONS: A 100% smoke-free law was more effective than a partial restriction law in reducing ACS admissions. An immediate effect was followed by a sustained decrease in ACS admissions. Smoke-free initiatives can be also effective in decreasing acute coronary events in developing countries.

Behavioral responses to ethanol in rats perinatally exposed to low lead levels.

Wistar rats were exposed to 220 ppm of lead (Pb) in the drinking water from conception to the end of the nursing period (postnatal day 25). Maternal blood Pb levels at this time were 25 microg/dl. Male offspring were tested at the age of 35 or 70 days. We studied the anxiolytic response to 0.5-2.0 g/kg ethanol in an elevated plus maze test and preference for increasing ethanol solutions (2%, 4%, and 6%, v/v) in a free-choice paradigm; we also determined basal blood levels of corticosterone. Results demonstrated that, at 35 days of age, experimental rats were hypersensitive to the anxiolytic effect of ethanol and showed greater voluntary intake of this drug. In addition, 35-day-old Pb-treated rats exhibited higher basal levels of corticosterone as compared with those of controls. These differences disappeared at 70 days. Our findings are discussed in terms of either Pb-induced alterations in the development of the CNS or higher levels of corticosterone in experimental animals. Possible Pb-ethanol effects interactions are also considered.

Spatial learning in rats exposed to acute ethanol intoxication on gestational day 8.

Pregnant Wistar rats were treated on gestational day 8 (GD 8) with two IP injections of either ethanol (2.9 g/kg in 24% v/v saline solution) or saline. Offspring were tested in the water-maze task at 45 or 90 days of age. The escape latencies of rats trained with a submerged escape platform at a fixed location were similar between control and experimental rats. Analyses of responses on a probe trial carried out 10 days after the training period, revealed that 90-day-old females prenatally exposed to alcohol were less likely to swim in the target region. No differences were observed in this free-swim trial in 45- and 90-day-old male, and 45-day-old female animals. Binding studies of low-affinity GABAA sites in the hippocampus showed an increase in affinity of [3H]GABAA for their binding sites in 90-day-old female offspring prenatally intoxicated with ethanol. Our results demonstrate that acute intoxication with ethanol on GD 8 did not modify acquisition but impaired the retention of spatial learning only in adult female rats. It is possible that the impaired retention will be consequence of higher GABAA receptor affinity.

Effects of acute ethanol intoxication during pregnancy on central dopaminergic system in male rats.

Pregnant albino rats received 2 IP injections, spaced by 4 h, of either ethanol (2.9 g/kg in 24% v/v saline solution) or saline, on gestational day (GD) 8. During adulthood, male rats prenatally exposed to alcohol exhibited an increased stereotyped behavioral response to 12 mg/kg of amphetamine (AMPH) or 1 mg/kg of apomorphine (APO), whereas the stereotypy induced by 6 mg/kg of AMPH showed no difference between control and experimental animals. Also, the hypoactivity response elicited by small doses of APO was not significantly affected by the prenatal treatment with alcohol. Analysis of dopaminergic function in the striatum and nucleus accumbens demonstrated no change on dopamine (DA) levels in both structures in alcohol pre-exposed 55- and 180-day-old rats. A reduction in striatum 3-4 dihydroxyphenylacetic acid levels was observed at both ages. These results indicate that an acute intoxication with alcohol on GD 8 induces a long-lasting decrease in striatal but not in nucleus accumbens DA metabolism. As a consequence, a lower striatal DA release might produce a compensatory supersensitivity of postsynaptic DA sites. This interpretation is consistent and correlates with behavioral results.