Non-exposed Animals Research Articles

Effect of chronic prenatal exposure to the food additive titanium dioxide E171 on respiratory activity in newborn mice.

Nanoparticles (NPs) possess unique properties that make their use valuable in all industries. Titanium dioxide (TiO2) NPs are extensively used as a white pigment in food (labeled under the European number E171) and personal care products, which creates a significant potential for chronic consumer exposure. Concerns about the potential toxic effects of TiO2 NPs have arisen, particularly in vulnerable populations, including pregnant women and infants. Recently, human materno-fetal transfer of E171 was demonstrated, and simultaneously, we reported that chronic prenatal exposure to reference P25 TiO2 NPs was found to alter the developing respiratory neural networks. In this study, using whole body plethysmography from postnatal day (P) 0 to P7, we assessed the respiratory function of newborn mice born to mothers fed with E171 during pregnancy. We also evaluated the potential alterations to respiratory centers by using brainstem-spinal cord electrophysiological recordings from P0 to P6. Our study reveals that E171-prenatally exposed animals displayed an abnormally elevated breathing rate from P3 onwards. From P5 to P6, the respiratory-related burst frequency generated by the isolated brainstem-spinal cord preparations was significantly higher in E171-exposed animals than in non-exposed animals. These findings demonstrate prenatal toxicity of E171 to the developing respiratory function and may contribute to policy-making regarding the use of TiO2 NPs.

Multigenerational inheritance of breathing deficits following perinatal exposure to titanium dioxide nanoparticles in the offspring of mice

BackgroundThe utilization of titanium dioxide nanoparticles (TIO2NPs) has experienced a significant surge in recent decades, and these particles are now commonly found in various everyday consumer products. Due to their small size, TIO2NPs can penetrate biological barriers and elicit adverse interactions with biological tissues. Notably, exposure of pregnant females to TIO2NPs during the perinatal period has been shown to disrupt the growth of offspring. Furthermore, this exposure induces epigenetic modifications in the DNA of newborns, suggesting the possibility of multigenerational effects. Thus, perinatal exposure to TIO2NPs may induce immediate metabolic impairments in neonates, which could be transmitted to subsequent generations in the long term.ResultsIn this study, we utilized perinatal exposure of female mice to TIO2NPs through voluntary food intake and observed impaired metabolism in newborn male and female F1 offspring. The exposed newborn mice exhibited reduced body weight gain and a slower breathing rate compared to non-exposed animals. Additionally, a higher proportion of exposed F1 newborns experienced apneas. Similar observations were made when the exposure was limited to the postnatal period, highlighting lactation as a critical period for the adverse effects of TIO2NPs on postnatal metabolism. Importantly, the breathing deficits induced by TIO2NPs were transmitted from F1 females to the subsequent F2 generation. Moreover, re-exposure of adult F1 females to TIO2NPs exacerbated the breathing deficits in newborn F2 males.ConclusionsOur findings demonstrate that perinatal exposure to TIO2NPs disrupts postnatal body weight gain and respiration in the offspring, and these deficits are transmissible to future generations.

Gestational paracetamol exposure induces core behaviors of neurodevelopmental disorders in infant rats and modifies response to a cannabinoid agonist in females

Paracetamol (PAR) is an over-the-counter analgesic/antipyretic used during pregnancy worldwide. Epidemiological studies have been associating gestational PAR exposure with neurobehavioral alterations in the progeny resembling autism spectrum disorders and attention-deficit hyperactivity disorder symptoms. The endocannabinoid (eCB) dysfunction was previously hypothesized as one of the modes of action by which PAR may harm the developing nervous system. We aimed to evaluate possible effects of gestational exposure to PAR on male and female rat's offspring behavior and if an acute injection of WIN 55,212–2 (WIN, 0.3 mg/kg), a non-specific cannabinoid agonist, prior to behavioral tests, would induce different effects in PAR exposed and non-exposed animals. Pregnant Wistar rats were gavaged with PAR (350 mg/kg/day) or water from gestational day 6 until delivery. Nest-seeking, open field, apomorphine-induced stereotypy, marble burying and three-chamber tests were conducted in 10-, 24-, 25- or 30-days-old rats, respectively. PAR exposure resulted in increased apomorphine-induced stereotyped behavior and time spent in the central area of the open field in exposed female pups. Additionally, it induced hyperactivity in the open field and increased marble burying behavior in both male and female pups. WIN injection modified the behavioral response only in the nest seeking test, and opposite effects were observed in control and PAR-exposed neonate females. Reported alterations are relevant for the neurodevelopmental disorders that have been associated with maternal PAR exposure and suggest that eCB dysfunction may play a role in the action by which PAR may harm the developing brain.

Single-cell Genomics: A Quantum Leap toward Understanding Complexity?

Single-cell Genomics: A Quantum Leap toward Understanding Complexity?

First study on response of astrocytes in alevines of red-bellied pacu (Piaractus brachypomus) to subchronic exposure to chlorpyrifos and trichlorfon.

Background and Aim:Organophosphate pesticides (OPs) used in agricultural production pose environmental and public health risks whenever non-target organisms are exposed to them. Oxon-type OPs, such as trichlorfon (TCF) and chlorpyrifos (CPF), are frequently used in Colombia and have been detected in water bodies in the vicinity of croplands; however, their effect on aquatic organisms, especially fish, is largely unknown. The neurotoxicity of OPs includes inhibition of esterase enzymes, neuronal damage, and increased glial reactivity. This study aimed to assess the astrocytic response in the brain tissue of juvenile red-bellied pacu (Piaractus brachypomus) exposed to TCF and CPF.Materials and Methods:A 25-day subchronic assay was conducted in which juvenile red-bellied pacu were exposed to CPF and TCF. After 25 days of exposure, the fish were killed and brain samples were collected and processed for immunohistochemistry to assess the morphology and reactivity of astrocytes; glial acidic fibrillary protein was used as a biomarker.Results:The brain samples from animals under subchronic exposure to OPs for 25 days showed higher cellular density as well as changes in astrocyte phenotype characterized by shortening of cytoplasmic projections, hypertrophy, and ameboid morphology compared to those from nonexposed animals. Similarly, astrocyte hyperreactivity was detected in the optic tectum and medial longitudinal fasciculus of the exposed group.Conclusion:Immunoreactivity of brain glial cells under subchronic exposure to OPs measured through immunohistochemical tests as well as OPs-induced neuropathology may be useful as a biomarker for monitoring environmental pollution. The results also indicate that P. brachypomus is a suitable biomonitoring model for studying neurotoxicological and neurodegenerative diseases.

Chronic nicotine increases midbrain dopamine neuron activity and biases individual strategies towards reduced exploration in mice

Long-term exposure to nicotine alters brain circuits and induces profound changes in decision-making strategies, affecting behaviors both related and unrelated to drug seeking and consumption. Using an intracranial self-stimulation reward-based foraging task, we investigated in mice the impact of chronic nicotine on midbrain dopamine neuron activity and its consequence on the trade-off between exploitation and exploration. Model-based and archetypal analysis revealed substantial inter-individual variability in decision-making strategies, with mice passively exposed to nicotine shifting toward a more exploitative profile compared to non-exposed animals. We then mimicked the effect of chronic nicotine on the tonic activity of dopamine neurons using optogenetics, and found that photo-stimulated mice adopted a behavioral phenotype similar to that of mice exposed to chronic nicotine. Our results reveal a key role of tonic midbrain dopamine in the exploration/exploitation trade-off and highlight a potential mechanism by which nicotine affects the exploration/exploitation balance and decision-making.

Inflammatory repercussions in female steroid responsive glands after perinatal exposure to bisphenol A and 17-β estradiol.

The mammary gland (MG) and female prostate are plastic reproductive organs which are highly responsive to hormones. Thus, endocrine disruptors, such as bisphenol A (BPA) and exogenous estrogens, negatively affect glandular homeostasis. In addition to previously described alterations, changes in inflammatory markers expression also trigger the development of a microenvironment that contributes to tumor progression. The current work aimed to evaluate the inflammatory responses of the MG and prostate gland to BPA (50 µg/kg) and 17-β estradiol (35 µg/kg) exposure during the perinatal window of susceptibility. The results showed that at 6 months of age there was an increase in the number of phospho-STAT3 (P-STAT3) positive cells in the female prostate from animals perinatally exposed to 50 µg/kg BPA daily. In addition, the number of macrophages increased in these animals in comparison with nonexposed animals, as shown by the F4/80 marker. Despite an increase in the incidence of lobuloalveolar and intraductal hyperplasia, the MG did not show any difference in the expression of the four inflammatory markers evaluated: tumor necrosis factor-α, COX-2, P-STAT3, and F4/80. Analysis of both glands from the same animal led to the conclusion that exposure to endocrine disruptors during the perinatal window of susceptibility leads to different inflammatory responses in different reproductive organs. As the prostate is more susceptible to these inflammatory mechanisms, it is reasonable to affirm that possible neoplastic alterations in this organ are related to changes in the inflammatory pattern of the stroma, a characteristic that is not evident in the MG.

Impact of e-cigarettes on colonic mucosa and the role of recovery: involvement of oxidative and inflammatory pathway.

Electronic cigarettes (e-cigarettes) (EC) are often advertised as a safer alternative to conventional cigarettes. Its widespread use has led to increased interest in its adverse health effects, thanks to few restrictions and a lack of regulatory guidelines. The study aimed to evaluate the influence of exposure to e-cigarette aerosol inhalation in rat colon model and conduct a follow-up after cessation of exposure. The experiment included 30 male adult Albino rats. The animals were divided into three groups: group I (control), non-exposed animals; group II (exposed), was exposed to electronic cigarette liquid vapor for four consecutive weeks; and group III (recovery), was followed up for another 4 weeks after exposure to an e-cigarette as exposed group and for the same duration. In the exposed group, malondialdehyde (MDA) and total nitric oxide (NO) increased significantly in colonic tissue, while superoxide dismutase (SOD) decreased. On histological examination, colonic mucosa showed distortion and loss of its epithelial lining with heavy inflammatory cell infiltration. Also, there was a significant decrease in periodic acid-Schiff-positive goblet cells and area percent of proliferating cell nuclear antigen expression. Tumor necrosis factor-alpha (TNFα) expression significantly increased in colonic mucosa. After 4 weeks of EC cessation, the colonic mucosal histological structure showed recovery with downregulated TNFα immunoexpression and restored oxidant/antioxidant balance. In conclusion, the usage of electronic cigarettes resulted in marked pathological alterations in the colonic mucosa, which could be attributed to oxidative and inflammatory stresses. In contrast, the cessation of exposure led to recovery.

Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice

Smoking has been associated with renal disease progression in ADPKD but the underlying deleterious mechanisms and whether it specifically worsens the cardiac phenotype remain unknown. To investigate these matters, Pkd1-deficient cystic mice and noncystic littermates were exposed to smoking from conception to 18 weeks of age and, along with nonexposed controls, were analyzed at 13–18 weeks. Renal cystic index and cyst-lining cell proliferation were higher in cystic mice exposed to smoking than nonexposed cystic animals. Smoking increased serum urea nitrogen in cystic and noncystic mice and independently enhanced tubular cell proliferation and apoptosis. Smoking also increased renal fibrosis, however this effect was much higher in cystic than in noncystic animals. Pkd1 deficiency and smoking showed independent and additive effects on reducing renal levels of glutathione. Systolic function and several cardiac structural parameters were also negatively affected by smoking and the Pkd1-deficient status, following independent and additive patterns. Smoking did not increase, however, cardiac apoptosis or fibrosis in cystic and noncystic mice. Notably, smoking promoted a much higher reduction in body weight in Pkd1-deficient than in noncystic animals. Our findings show that smoking aggravated the renal and cardiac phenotypes of Pkd1-deficient cystic mice, suggesting that similar effects may occur in human ADPKD.

Effect of second-hand smoke on the immunological parameters of wistar rats and their offspring

The literature covers multiple negative effects of active and passive tobacco smoking upon the human body and experimental animals. Much lesser attention is given to the features of the immune system in offspring from the passively smoking experimental animals. In previous works, we studied physiological and immunological parameters in the infant rats born from passively smoking rats. The present work expands the scope of this direction and is devoted to assessment of immunological parameters in passively smoking pregnant rats and their offspring. Quantitative determination of immunological parameters was carried out in pregnant Wistar rats exposed to passive tobacco smoking and in 65 pup rats from smoke-exposed and nonexposed animals. The experimental rats were exposed to tobacco smoke for 8 hours from the 1st to the 20th day of pregnancy. In all animals, the body weight, thymus and spleen, the number of white blood cells, thymocytes, splenocytes, and myelocaryocytes were determined. On the 20th day of pregnancy, the smoking rats showed a significant decrease in the weight of animals, the number of thymocytes and myelocaryocytes. A decreased body mass of animals and their thymus glands, lower number of thymocytes were registered in pup rats born from smoking females as compared with control animals. These changes in immunological parameters may be based on a number of possible reasons. On the one hand, tobacco smoke promotes activation of free-radical processes with a simultaneously decreased efficiency of antioxidant mechanisms. This activation may result from exposure to the components of tobacco smoke, in particular, chromium, as a metal of variable valence, as well as benzene, which is transformed by the free-radical oxidation mechanisms. On the other hand, some tobacco smoke components may promote apoptosis which plays a significant role in the cellular exhaustion of immunogenesis system. Moreover, a decreased number of thymocytes may be caused by their migration from cortical areas to the medulla, followed by release into bloodstream. Thus, the results obtained indicate that the detected changes in these parameters are more pronounced in pregnant rats who were exposed to tobacco smoke and their offspring, and expand the knowledge of changes in the immune system in the offspring of passively smoking animals. The presented data may present a basis for development of drugs that reduce toxic effect of ecotoxicants, including passive tobacco smoking.

Interferon-γ Response of Mycobacterium avium subsp. paratuberculosis Infected Goats to Recombinant and Synthetic Mycobacterial Antigens.

Despite its potential for early diagnosis of Mycobacterium avium subsp. paratuberculosis (MAP) infection, the IFN-γ release assay is not used routinely, because of low specificity of the established crude antigen preparation Johnin (PPDj). Limited data are available assessing the potential of MAP-derived protein and lipopeptide antigens to replace PPDj in assays for goats, while cattle and sheep have been studied more extensively. Furthermore, MAP infection is claimed to interfere with the diagnosis of bovine tuberculosis when other crude antigen preparations (PPDb, PPDa) are applied. In this study, the diagnostic potential of MAP-derived recombinant protein antigens, synthetic MAP lipopentapeptides and of Mycobacterium bovis-specific peptide cocktails was assessed compared to crude mycobacterial antigen preparations in experimentally infected goats. Goats were inoculated with MAP, or Mycobacterium avium subsp. hominissuis (MAH) as surrogate for environmental mycobacteria, non-exposed animals served as controls. Mycobacterium avium Complex-specific antibody and PPDj-induced IFN-γ responses were monitored in vivo. Infection status was assessed by pathomorphological findings and bacteriological tissue culture at necropsy 1 year after inoculation. The IFN-γ response to 13 recombinant protein antigens of MAP, two synthetic MAP lipopentapeptides and three recombinant peptide cocktails of Mycobacterium bovis was investigated at three defined time points after infection. At necropsy, MAP or MAH infection was confirmed in all inoculated goats, no signs of infection were found in the controls. Antibody formation was first detected 3–6 weeks post infection (wpi) in MAH-inoculated and 11–14 wpi in the MAP-inoculated goats. Maximum PPDj-induced IFN-γ levels in MAH and MAP exposed animals were recorded 3–6 and 23–26 wpi, respectively. Positive responses continued with large individual variation. Antigens Map 0210c, Map 1693c, Map 2020, Map 3651cT(it), and Map 3651c stimulated increased whole blood IFN-γ levels in several MAP-inoculated goats compared to MAH inoculated and control animals. These IFN-γ levels correlated with the intensity of the PPDj-induced responses. The two synthetic lipopentapeptides and the other MAP-derived protein antigens had no discriminatory potential. Stimulation with Mycobacterium bovis peptide cocktails ESAT6-CFP10, Rv3020c, and Rv3615c did not elicit IFN-γ production. Further work is required to investigate if test sensitivity will increase when mixtures of the MAP-derived protein antigens are applied.

Resilience to stress and sex-specific remodeling of microglia and neuronal morphology in a rat model of anxiety and anhedonia

Prenatal exposure to stress or glucocorticoids (GC) is associated with the appearance of psychiatric diseases later in life. Microglia, the immune cells of the brain, are altered in stress-related disorders.Synthetic GC such as dexamethasone (DEX) are commonly prescribed in case of preterm risk labour in order to promote fetal lung maturation. Recently, we reported long-lasting differences in microglia morphology in a model of in utero exposure to DEX (iuDEX), that presents an anxious phenotype. However, it is still unclear if stress differentially affects iuDEX males and females.In this work, we evaluated how iuDEX animals of both sexes cope with chronic mild stress for 2 weeks. We evaluated emotional behavior and microglia and neuronal morphology in the dorsal hippocampus (dHIP) and nucleus accumbens (NAc), two brain regions involved in emotion-related disorders. We report that males and females prenatally exposed to DEX have better performance in anxiety- and depression-related behavioral tests after chronic stress exposure in adulthood than non-exposed animals. Interestingly, iuDEX animals present sex-dependent changes in microglia morphology in the dHIP (hypertrophy in females) and in the NAc (atrophy in females and hypertrophy in males). After chronic stress, these cells undergo sex-specific morphological remodeling. Paralleled to these alterations in cytoarchitecture of microglia, we report inter-regional differences in dendritic morphology in a sex-specific manner. iuDEX females present fewer complex neurons in the NAc, whereas iuDEX males presented less complex neuronal morphology in the dHIP. Interestingly, these alterations were modified by stress exposure.Our work shows that stressful events during pregnancy can exert a preserved sex-specific effect in adulthood. Although the role of the observed cellular remodeling is still unknown, sex-specific differences in microglia plasticity induced by long-term stress exposure may anticipate differences in drug efficacy in the context of stress-induced anxiety- or depression-related behaviors.

Giardia duodenalis pathogenicity on immunosuppressed animal model.

Giardiasis is the major water-borne diarrheal disease present worldwide caused by the common intestinal parasite, Giardia duodenalis. This work aims to investigate the effect of G. duodenalis infection pathogenicity in immunosuppressed animals through histopathological examination. A total of 45 BALB/c mice were divided into four groups; G1 (negative control), G2 (healthy animals exposed to Giardia); G3 (immunosuppressed animals exposed to Giardia), and G4 (non-exposed immunosuppressed animals). Our study revealed that G3 was the most affected group with an infection rate of 100%. The animals showed general weakness, soft stool, and high death rate with severe histopathological changes in the duodenum and mild degenerative changes in hepatic tissues. In G2, the maximal lesions in both duodenum and liver were on the 11th day. We spotted damage in the villi, edema in the central core, and submucosa, in addition to increased cellular infiltration with inflammation in lamina propria. The presence of the parasites within the villi and the lumen was clear. Most of the hepatocytes revealed hydropic and fatty changes, also dilated congested central veins and edema were observed. G3 changes were more intense than G2 with massive Giardia trophozoites between the intestinal villi, lumen, and extensive fatty liver degeneration. Immune suppression plays a significant role in the severity of injury with the Giardia parasites in duodenum and liver cells.

Nanopolystyrene particles at environmentally relevant concentrations causes behavioral and biochemical changes in juvenile grass carp (Ctenopharyngodon idella)

The biometric, behavioral and biochemical toxicity of polystyrene nanoplastics (PS NPs) in aquatic freshwater vertebrates and in environmentally relevant concentrations remains poorly known. Thus, using different toxicity biomarkers we tested the hypothesis that the exposure of Ctenopharyngodon idella juveniles to small PS NPs concentrations (0.04 ng/L, 34 ng/L and 34 μg/L), for a short period-of-time, may affect their growth/development, individual and collective behavior, and biochemical parameters. Animals exposed to NPs did not show increased biometric parameters (i.e.: body biomass, total and standard length, peduncle height, head height and visceral somatic and hepatosomatic indices). Despite the lack of damage on the locomotor (open field test) and visual (visual stimulus test) abilities of the evaluated fish, the expected increase in locomotor activity during the vibratory stimulus test was not evident in animals exposed to NPs. Non-exposed animals were the only ones showing increased activity/locomotion time in the presence of the predatory stimulus during the individual anti-predatory response test. The behavior of animals directly confronted with a potential predator has evidenced the influence of NPs on shoals’ aggregation and on the distance kept by individuals from the predatory stimulus. These changes were associated with PS NPs accumulation in animals' brains, oxidative stress and increased acetylcholinesterase activity (hepatic and cerebral). Therefore, the current study has confirmed the initial hypothesis and showed that, even at low concentrations, PS NPs can affect the health of C. idella individuals at early life stage.

Combinatorial Discriminant Analysis Applied to RNAseq Data Reveals a Set of 10 Transcripts as Signatures of Exposure of Cattle to Mycobacterium avium subsp. paratuberculosis.

Simple SummaryParatuberculosis or Johne’s disease (JD) in cattle is a chronic granulomatous gastroenteritis caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP). JD is not treatable; therefore, the early identification of infected animals is a key point in reducing its incidence worldwide. In this paper, combinatorial discriminant analysis was applied to transcriptomic data to find a small set of differentially expressed genes able to discriminate between exposed cattle from non-exposed animals. Results of the discriminant analysis identified 10 transcripts that differentiate between ELISA-negative animals belonging to paratuberculosis-positive herds that were potentially exposed to MAP and negative-unexposed animals belonging to paratuberculosis-negative herds. The 10 transcript signature was also used for the classification of 5 cattle positive-for-MAP infection samples, with the underlying hypothesis that their transcriptional profile should be closer to potentially exposed animals than to controls. The same set of 10 transcripts was able to differentiate ELISA-negative unexposed animals from positive animals based on the results of the ELISA test for bovine paratuberculosis and faecal culture. In conclusion, these findings suggest the possible use of the identified RNA expression signature as a new diagnostic test for paratuberculosis. Paratuberculosis or Johne’s disease in cattle is a chronic granulomatous gastroenteritis caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP). Paratuberculosis is not treatable; therefore, the early identification and isolation of infected animals is a key point to reduce its incidence. In this paper, we analyse RNAseq experimental data of 5 ELISA-negative cattle exposed to MAP in a positive herd, compared to 5 negative-unexposed controls. The purpose was to find a small set of differentially expressed genes able to discriminate between exposed animals in a preclinical phase from non-exposed controls. Our results identified 10 transcripts that differentiate between ELISA-negative, clinically healthy, and exposed animals belonging to paratuberculosis-positive herds and negative-unexposed animals. Of the 10 transcripts, five (TRPV4, RIC8B, IL5RA, ERF, CDC40) showed significant differential expression between the three groups while the remaining 5 (RDM1, EPHX1, STAU1, TLE1, ASB8) did not show a significant difference in at least one of the pairwise comparisons. When tested in a larger cohort, these findings may contribute to the development of a new diagnostic test for paratuberculosis based on a gene expression signature. Such a diagnostic tool could allow early interventions to reduce the risk of the infection spreading.

The BET Bromodomain Inhibitor I-BET-151 Induces Structural and Functional Alterations of the Heart Mitochondria in Healthy Male Mice and Rats.

The bromodomain and extra-terminal domain family inhibitors (BETi) are a promising new class of anticancer agents. Since numerous anticancer drugs have been correlated to cardiomyopathy, and since BETi can affect non-cancerous tissues, we aimed to investigate in healthy animals any ultrastructural BETi-induced alterations of the heart as compared to skeletal muscle. Male Wistar rats were either treated during 3 weeks with I-BET-151 (2 or 10 mg/kg/day) (W3) or treated for 3 weeks then allowed to recover for another 3 weeks (W6) (3-weeks drug washout). Male C57Bl/6J mice were only treated during 5 days (50 mg/kg/day). We demonstrated the occurrence of ultrastructural alterations and progressive destruction of cardiomyocyte mitochondria after I-BET-151 exposure. Those mitochondrial alterations were cardiac muscle-specific, since the skeletal muscles of exposed animals were similar in ultrastructure presentation to the non-exposed animals. I-BET-151 decreased the respiration rate of heart mitochondria in a dose-dependent manner. At the higher dose, it also decreased mitochondrial mass, as evidenced by reduced right ventricular citrate synthase content. I-BET-151 reduced the right and left ventricular fractional shortening. The concomitant decrease in the velocity-time-integral in both the aorta and the pulmonary artery is also suggestive of an impaired heart function. The possible context-dependent cardiac side effects of these drugs have to be appreciated. Future studies should focus on the basic mechanisms of potential cardiovascular toxicities induced by BETi and strategies to minimize these unexpected complications.

Study of the effects of zinc pyrithione in biochemical parameters of the Polychaeta Hediste diversicolor: evidences of neurotoxicity at ecologically relevant concentrations.

Nowadays there are various groups of biocidal chemical agents, which can be used in diverse areas, such as personal hygiene, disinfection, antiparasitic action, and also in antifouling mixtures or paints. The versatility and efficacy of some of these agents favors their use and ultimate release into the aquatic environment, where they may still exert toxic activity. Zinc pyrithione is classified as a metal biocide with bactericidal, algicidal, and fungicidal actions. It has been formulated in antifouling paints, which prevent the formation of biofilms in submerged structures, and has also been used for dermocosmetic purposes, in shampoos for the treatment of dandruff and seborrhea. Some of the uses of zinc pyrithione are responsible for its direct release as flakes that reach the bottom sediments, especially in estuarine areas. Considering this fate, the ecotoxicity assessment of its effects towards sediment organisms, namely Polychaetous species, is extremely important. The present study characterized the acute potential toxicity of zinc pyrithione in terms of parameters of oxidative stress (catalase, glutathione S-transferases (GSTs), and thiobarbituric acid reactive substances (TBARS)), and neurotoxicity (acetylcholinesterase) which were evaluated in individuals of the polychaete Hediste diversicolor. Regarding the results obtained, only the activity of GSTs and AChE was significantly altered in relation to non-exposed animals. This set of results indicates that oxidative stress did not occur.

Chronic copper treatment prevents the liver critical balance transcription response induced by acetaminophen

The independent toxic effects of copper and acetaminophen are among the most studied topics in liver toxicity. Here, in an animal model of Cebus capucinus chronically exposed to high dietary copper, we assessed clinical and global transcriptional adaptations of the liver induced by a single high dose of acetaminophen. The experiment conditions were chosen to resemble a close to human real-life situation of exposure to both toxic stimuli. The clinical parameters and histological analyses indicated that chronic copper administration does not induce liver damage and may have a protective effect in acetaminophen challenge. Acetaminophen administration in previously non-exposed animals induced down-regulation of a complex network of gene regulators, highlighting the putative participation of the families of gene regulators HNF, FOX, PPAR and NRF controlling this process. This gene response was not observed in animals that previously received chronic oral copper, suggesting that this metal induces a transcriptional adaptation that may protect against acetaminophen toxicity, a classical adaptation response termed preconditioning of the liver.

Changes to Neural Activation Patterns (c-fos Labeling) in Chinchilla Auditory Midbrain following Neonatal Exposure to an Enhanced Sound Environment.

Sensory brain regions show neuroplastic changes following deficits or experimental augmentation of peripheral input during a neonatal period. We have previously shown reorganization of cortical tonotopic maps after neonatal cochlear lesions or exposure to an enhanced acoustic environment. Such experiments probe the cortex and show reorganization, but it is unclear if such changes are intrinsically cortical or reflect projections from modified subcortical regions. Here, we ask whether an enhanced neonatal acoustic environment can induce midbrain (inferior colliculus (IC)) changes. Neonatal chinchillas were chronically exposed to a 70 dB SPL narrowband (2 ± 0.25 kHz) sound stimulus for 4 weeks. In line with previous studies, we hypothesized that such exposure would induce widening of the 2 kHz tonotopic map region in IC. To probe c-fos expression in IC (central nucleus), sound-exposed and nonexposed animals were stimulated with a 2 kHz stimulus for 90 minutes. In sound-exposed subjects, we find no change in the width of the 2 kHz tonotopic region; thus, our hypothesis is not supported. However, we observed a significant increase in the number of c-fos-labeled neurons over a broad region of best frequencies. These data suggest that neonatal sound exposure can modify midbrain regions and thus change the way neurons in IC respond to sound stimulation.

Chronic Exposure to External Low-Dose Gamma Radiation Induces an Increase in Anti-inflammatory and Anti-oxidative Parameters Resulting in Atherosclerotic Plaque Size Reduction in ApoE-/- Mice.

Populations living in radiation-contaminated territories, such as Chernobyl and Fukushima, are chronically exposed to external gamma radiation and internal radionuclide contamination due to the large amount of 137Cs released in the environment. The effect of chronic low-dose exposure on the development of cardiovascular diseases remains unclear. Previously reported studies have shown that low-dose radiation exposure could lead to discrepancies according to dose rate. In this study, we examined the effect of very low-dose and dose-rate chronic external exposure on atherosclerosis development. ApoE-/- mice were chronically irradiated with a gamma source for 8 months at two different dose rates, 12 and 28 μGy/h, equivalent to dose rates measured in contaminated territories, with a cumulative dose of 67 and 157 mGy, respectively. We evaluated plaque size and phenotype, inflammatory profile and oxidative stress status. The results of this study showed a decrease in plaque sizes and an increase in collagen content in ApoE-/- mice exposed to 28 μGy/h for 8 months compared to nonexposed animals. The plaque phenotype was associated with an increase in anti-inflammatory and anti-oxidative gene expression. These results suggest that chronic low-dose gamma irradiation induces an upregulation of organism defenses leading to a decrease in inflammation and plaque size. To our knowledge, this is the first study to describe the possible effect of chronic external very low-dose ionizing radiation exposure for 8 months. This work could help to identify the potential existence of a dose threshold, below that which harmful effects are not exhibited and beneficial effects are potentially observed. Furthermore, these findings permit consideration of the importance of dose rate in radiation protection.