Toxicity of chronic ethanol ingestion and superoxide radical formation on seminal vesicles of rats

The toxic effects of chronic ethanol ingestion were evaluated in male adult rats for 300 days. The animals were divided into three groups: the controls received only tap water as liquid diet; the chronic ethanol ingestion group received only ethanol solution (30%) in semivoluntary research; and the withdrawal group received the same treatment as chronic ethanol-treated rats until 240 days, after which they reverted to drinking water. Chronic ethanol ingestion induced increased lipoperoxide levels and acid phosphatase activities in seminal vesicles. Cu-Zn superoxide dismutase (SOD) decreased from its basal level 70.8 +/- 3.5 to 50.4 +/- 1.6 U/mg protein at 60 days of chronic ethanol ingestion. As changes in GSH-PX activity were observed in rats after chronic ethanol ingestion, while SOD activities were decreased in these animals, it is assumed that superoxide anion elicits lipoperoxide formation and induces cell damage before being converted to hydrogen peroxide by SOD. Ethanol withdrawal induced increased SOD activity and reduced seminar vesicle damage, indicating that the toxic effects were reversible, since increased SOD activity was adequate to scavenge superoxide radical formation. Superoxide radical is an important intermediate in the toxicity of chronic ethanol ingestion. Copyright (C) 1996 Elsevier B.V. Ltd

Ultrastructural changes on the epithelial cells of uterine tubes of Wistar rats after chronic ethanol ingestion

The present paper describes the morphological alterations of the epithelial layer of the uterine tubes of rats submitted to experimental chronic alcoholism using anatomical, histological, ultrastructural and morphometric methods. Sixty adult rats (Rattus norvegicus albinus) at the same age (3 months) and with a mean body weight of 228 g were divided into two groups. The control group received solid diet (Purina rat chow) and tap water ad libitum. The alcoholic group received the same solid diet and was allowed to drink only sugar cane brandy dissolved in 30° Gay Lussac (v/v). After periods of 90, 180 and 270 days of treatment animals at normal estrus were anaesthetised with ethyl ether, weighed and sacrificed. Subsequently, the uterine tubes were dissected, weighed and prepared for TEM and SEM methods. The final mean body weights were similar in the control and alcoholic groups. The morphometric analysis showed no difference between control and alcoholic epithelial height. The alcoholic animals showed ultrastructural alterations: intense lipid droplet and lysosomes accumulation, dilated rough endoplasmic reticulum cisternae and vacuolization in both periods of treatment. It was concluded that alcohol acts as a toxin on the epithelial layer of the uterine tubes of rats.

Morphological alterations on the prostate of Calomys callosus submitted to chronic ethanol ingestion

The objective of the present study was to assess the possible toxic effects of chronic alcohol ingestion on the ultrastructure of the glandular epithelium of the prostate of the rodent Calomys callosus, in order to contribute to the understanding of the consequences of alcohol abuse for the morphology of the male reproductive apparatus. Sixteen adult animals aged three months were divided into two experimental groups. The control group received a solid diet and tap water, and the alcoholic group received the same solid diet and ethanol P.A. diluted 20% in water (v/v). After 120 days of treatment, all animals were anesthetized, weighed and sacrificed. At the end of treatment, mean body weight did not differ between control and alcoholic animals. The prostate epithelial cells of the alcoholic group showed intense atrophy and ultrastructural alterations such as the presence of lipid droplets, altered nuclei, ruptured mitochondrial cristae, and intense dilatation of the cisterns of the granular endoplasmic reticulum. It was concluded that 20% ethanol provokes marked lesions on the epithelium of the prostate probably interfering on the glandular secretion.

Chronic Ethanol Consumption Alters All-Trans-Retinoic Acid Concentration and Expression of Their Receptors on the Prostate: A Possible Link Between Alcoholism and Prostate Damage

Background: Ethanol (EtOH) alters the all-trans-retinoic acid (ATRA) levels in some tissues. Retinol and ATRA are essential for cell proliferation, differentiation, and maintenance of prostate homeostasis. It has been suggested that disturbances in retinol/ATRA concentration as well as in the expression of retinoic acid receptors (RARs) contribute to benign prostate hyperplasia and prostate cancer. This study aimed to evaluate whether EtOH consumption is able to alter retinol and ATRA levels in the plasma and prostate tissue as well as the expression of RARs, cell proliferation, and apoptosis index. Methods: All animals were divided into 4 groups (n = 10/group). UChA: rats fed 10% (v/v) EtOH ad libitum; UChACo: EtOH-naïve rats without access to EtOH; UChB: rats fed 10% (v/v) EtOH ad libitum; UChBCo: EtOH-naïve rats without access to EtOH. Animals were euthanized by decapitation after 60 days of EtOH consumption for high-performance liquid chromatography and light microscopy analysis. Results: EtOH reduced plasma retinol concentration in both UChA and UChB groups, while the retinol concentration was not significantly different in prostate tissue. Conversely, plasma and prostate ATRA levels increased in UChB group compared with controls, beyond the up-regulation of RARβ and -γ in dorsal prostate lobe. Additionally, no alteration was found in cell proliferation and apoptosis index involving dorsal and lateral prostate lobe. Conclusions: We conclude that EtOH alters the plasma retinol concentrations proportionally to the amount of EtOH consumed. Moreover, high EtOH consumption increases the concentration of ATRA in plasma/prostate tissue and especially induces the RARβ and RARγ in the dorsal prostate lobe. EtOH consumption and increased ATRA levels were not associated with cell proliferation and apoptosis in the prostate. © 2012 by the Research Society on Alcoholism.

Apoptosis of Purkinje and Granular Cells of the Cerebellum Following Chronic Ethanol Intake

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Testosterone Therapy Differently Regulates the Anti- and Pro-Inflammatory Cytokines in the Plasma and Prostate of Rats Submitted to Chronic Ethanol Consumption (UChB)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Impact of Chronic Neonicotinoid Exposure on Honeybee Colony Performance and Queen Supersedure

Background Honeybees provide economically and ecologically vital pollination services to crops and wild plants. During the last decade elevated colony losses have been documented in Europe and North America. Despite growing consensus on the involvement of multiple causal factors, the underlying interactions impacting on honeybee health and colony failure are not fully resolved. Parasites and pathogens are among the main candidates, but sublethal exposure to widespread agricultural pesticides may also affect bees. Methodology/Principal Findings To investigate effects of sublethal dietary neonicotinoid exposure on honeybee colony performance, a fully crossed experimental design was implemented using 24 colonies, including sister-queens from two different strains, and experimental in-hive pollen feeding with or without environmentally relevant concentrations of thiamethoxam and clothianidin. Honeybee colonies chronically exposed to both neonicotinoids over two brood cycles exhibited decreased performance in the short-term resulting in declining numbers of adult bees (−28%) and brood (−13%), as well as a reduction in honey production (−29%) and pollen collections (−19%), but colonies recovered in the medium-term and overwintered successfully. However, significantly decelerated growth of neonicotinoid-exposed colonies during the following spring was associated with queen failure, revealing previously undocumented long-term impacts of neonicotinoids: queen supersedure was observed for 60% of the neonicotinoid-exposed colonies within a one year period, but not for control colonies. Linked to this, neonicotinoid exposure was significantly associated with a reduced propensity to swarm during the next spring. Both short-term and long-term effects of neonicotinoids on colony performance were significantly influenced by the honeybees’ genetic background. Conclusions/Significance Sublethal neonicotinoid exposure did not provoke increased winter losses. Yet, significant detrimental short and long-term impacts on colony performance and queen fate suggest that neonicotinoids may contribute to colony weakening in a complex manner. Further, we highlight the importance of the genetic basis of neonicotinoid susceptibility in honeybees which can vary substantially.

Chronic, topical exposure to benzo[a]pyrene induces relatively high steady-state levels of DNA adducts in target tissues and alters kinetics of adduct loss.

Carcinogen-DNA adduct measurements may become useful biomarkers of effective dose and/or early effect. However, validation of this biomarker is required at several levels to ensure that human exposure and response are accurately reflected. Important in this regard is an understanding of the relative biomarker levels in target and nontarget organs and the response of the biomarker under the chronic, low-dose conditions to which humans are exposed. We studied the differences between single and chronic topical application of benzo[a]pyrene (BAP) on the accumulation and removal of BAP-DNA adducts in skin, lung, and liver. Animals were treated with BAP at 10, 25, or 50 nMol topically once or twice per week for as long as 15 weeks. Animals were sacrificed either at 24, 48, or 72 hr after the last dose at 1 and 30 treatments, and after 24 hr for all other treatment groups. Adduct levels increased with increasing dose, but the slope of the dose-response was different in each organ. At low doses, accumulation was linear in skin and lung, but at high doses the adduct levels in the lung increased dramatically at the same time when the levels in the skin reached apparent steady state. In the liver adduct, levels were lower than in target tissues and apparent steady-state adduct levels were reached rapidly, the maxima being independent of dose, suggesting that activating metabolism was saturated in this organ. Removal of adducts from skin, the target organ, was more rapid following single treatment than with chronic exposure. This finding is consistent with earlier data, indicating that some areas of the genome are more resistant to repair. Thus, repeated exposure and repair cycles would be more likely to cause an increase in the proportion of carcinogen-DNA adducts in repair-resistant areas of the genome. These findings indicate that single-dose experiments may underestimate the potential for carcinogenicity for compounds that follow this pattern.

Decreased brain reward produced by ethanol withdrawal.

Abstinence from chronic administration of various drugs of abuse such as ethanol, opiates, and psychostimulants results in withdrawal syndromes largely unique to each drug class. However, one symptom that appears common to these withdrawal syndromes in humans is a negative affective/motivational state. Prior work in rodents has shown that elevations in intracranial self-stimulation (ICSS) reward thresholds provide a quantitative index that serves as a model for the negative affective state during withdrawal from psychostimulants and opiates. The current study sought to determine whether ICSS threshold elevations also accompany abstinence from chronic ethanol exposure sufficient to induce physical dependence. Rats prepared with stimulating electrodes in the lateral hypothalamus were trained in a discrete-trial current-intensity ICSS threshold procedure; subsequently they were subjected to chronic ethanol administration in ethanol vapor chambers (average blood alcohol level of 197 mg/dl). A time-dependent elevation in ICSS thresholds was observed following removal from the ethanol, but not the control, chambers. Thresholds were significantly elevated for 48 hr after cessation of ethanol exposure, with peak elevations observed at 6-8 hr. Blood alcohol levels were directly correlated with the magnitude of peak threshold elevation. Ratings of traditional overt signs of withdrawal showed a similar time course of expression and resolution. The results suggest that decreased function of reward systems (elevations in reward thresholds) is a common element of withdrawal from chronic administration of several diverse classes of abused drugs.