When pharmaceutical drugs become environmental pollutants: Potential neural effects and underlying mechanisms

2022 ◽  
Vol 205 ◽  
pp. 112495
Author(s):  
Pascal Vaudin ◽  
Corinne Augé ◽  
Nathalie Just ◽  
Sakina Mhaouty-Kodja ◽  
Stéphane Mortaud ◽  
...  
2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ting Xu ◽  
Jing Zhao ◽  
Zhifa Xu ◽  
Ruijie Pan ◽  
Daqiang Yin

Abstract Pentachlorophenol (PCP) is a typical toxicant and prevailing pollutant whose toxicity has been broadly investigated. However, previous studies did not specifically investigate the underlying mechanisms of its developmental toxicity. Here, we chose zebrafish embryos as the model, exposed them to 2 different concentrations of PCP, and sequenced their entire transcriptomes at 10 and 24 hours post-fertilization (hpf). The sequencing analysis revealed that high concentrations of PCP elicited systematic responses at both time points. By combining the enrichment terms with single genes, the results were further analyzed using three categories: metabolism, transporters, and organogenesis. Hyperactive glycolysis was the most outstanding feature of the transcriptome at 10 hpf. The entire system seemed to be hypoxic, although hypoxia-inducible factor-1α (HIF1α) may have been suppressed by the upregulation of prolyl hydroxylase domain enzymes (PHDs). At 24 hpf, PCP primarily affected somitogenesis and lens formation probably resulting from the disruption of embryonic body plan at earlier stages. The proposed underlying toxicological mechanism of PCP was based on the crosstalk between each clue. Our study attempted to describe the developmental toxicity of environmental pollutants from a systematic view. Meanwhile, some features of gene expression profiling could serve as markers of human health or ecological risk.


2021 ◽  
Vol 11 ◽  
Author(s):  
Regena Xin Yi Chua ◽  
Michelle Jia Yu Tay ◽  
Delicia Shu Qin Ooi ◽  
Kewin Tien Ho Siah ◽  
Elizabeth Huiwen Tham ◽  
...  

Both allergic diseases and neurodevelopmental disorders are non-communicable diseases (NCDs) that not only impact on the quality of life and but also result in substantial economic burden. Immune dysregulation and inflammation are typical hallmarks in both allergic and neurodevelopmental disorders, suggesting converging pathophysiology. Epidemiological studies provided convincing evidence for the link between allergy and neurodevelopmental diseases such as attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Possible factors influencing the development of these disorders include maternal depression and anxiety, gestational diabetes mellitus, maternal allergic status, diet, exposure to environmental pollutants, microbiome dysbiosis, and sleep disturbances that occur early in life. Moreover, apart from inflammation, epigenetics, gene expression, and mitochondrial dysfunction have emerged as possible underlying mechanisms in the pathogenesis of these conditions. The exploration and understanding of these shared factors and possible mechanisms may enable us to elucidate the link in the comorbidity.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jia Yang ◽  
Zhaoxu Lu ◽  
Zhichao Liu ◽  
Li Wang ◽  
Mei Qiang

Polycyclic aromatic hydrocarbons (PAHs) are known environmental pollutants. Studies are very limited regarding the impacts of paternal PAHs exposure on birth outcomes as well as the underpinning mechanisms in human. In this study, 302 reproductive-aged males (22–46 years old) were enrolled and demographic informatics data were obtained by questionnaires. The levels of urinary hydroxylated PAHs (OH-PAHs) were assessed by ultra-high performance liquid chromatography-tandem mass spectrometry; and methylation levels of the imprinting genes H19, Meg3, and Peg3 of sperm DNA were evaluated via bisulfite pyrosequencing. The analysis of the correlation between OH-PAHs levels and methylation levels of imprinting genes showed that OH-PAHs are correlated with some CpG sites in H19, Peg3, and Meg3. To further investigate an association of urinary OH-PAHs with birth outcomes, follow-up study of wives of these subjects has been performed for 1–3 years. As the result, a total of 157 babies were born. The birth outcomes parameters including birth weight (BW), length (BL), and ponderal index (PI) were recorded. The further analysis of generalized estimating equation indicated a negative correlation between urinary total OH-PAHs levels and newborn BW (β = −0.081, p = 0.020); but this association has not been found for BL and PI. Furthermore, a logistic regression analysis was employed for examining associations of the methylation of imprinting genes with birth outcomes parameters, which indicated a negative correlation between BW and H19, namely, each unit percent (%) elevation in methylation of H19 (but not Peg3 and Meg3) was significantly associated with a 0.135 g reduction of BW (β = −0.135; 95% CI 0.781–0.978). Putting together, these results show that paternal non-occupational environmental exposure to PAHs is associated with newborn BW. And imprinting gene H19 methylation may be involved in the underlying mechanisms. This study in human population adds a support for previous animal study and implies that environmental impact on the offspring through paternal pathway.


Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 106
Author(s):  
Camino San Martin Ruano ◽  
Francisco Miralles ◽  
Céline Méhats ◽  
Daniel Vaiman

Oxidative stress (OS) plays a pivotal role in placental development; however, abnormal loads in oxidative stress molecules may overwhelm the placental defense mechanisms and cause pathological situations. The environment in which the mother evolves triggers an exposure of the placental tissue to chemical, physical, and biological agents of OS, with potential pathological consequences. Here we shortly review the physiological and developmental functions of OS in the placenta, and present a series of environmental pollutants inducing placental oxidative stress, for which some insights regarding the underlying mechanisms have been proposed, leading to a recapitulation of the noxious effects of OS of environmental origin upon the human placenta.


Author(s):  
D.N. Collins ◽  
J.N. Turner ◽  
K.O. Brosch ◽  
R.F. Seegal

Polychlorinated biphenyls (PCBs) are a ubiquitous class of environmental pollutants with toxic and hepatocellular effects, including accumulation of fat, proliferated smooth endoplasmic recticulum (SER), and concentric membrane arrays (CMAs) (1-3). The CMAs appear to be a membrane storage and degeneration organelle composed of a large number of concentric membrane layers usually surrounding one or more lipid droplets often with internalized membrane fragments (3). The present study documents liver alteration after a short term single dose exposure to PCBs with high chlorine content, and correlates them with reported animal weights and central nervous system (CNS) measures. In the brain PCB congeners were concentrated in particular regions (4) while catecholamine concentrations were decreased (4-6). Urinary levels of homovanillic acid a dopamine metabolite were evaluated (7).Wistar rats were gavaged with corn oil (6 controls), or with a 1:1 mixture of Aroclor 1254 and 1260 in corn oil at 500 or 1000 mg total PCB/kg (6 at each level).


2008 ◽  
Vol 44 ◽  
pp. 11-26 ◽  
Author(s):  
Ralph Beneke ◽  
Dieter Böning

Human performance, defined by mechanical resistance and distance per time, includes human, task and environmental factors, all interrelated. It requires metabolic energy provided by anaerobic and aerobic metabolic energy sources. These sources have specific limitations in the capacity and rate to provide re-phosphorylation energy, which determines individual ratios of aerobic and anaerobic metabolic power and their sustainability. In healthy athletes, limits to provide and utilize metabolic energy are multifactorial, carefully matched and include a safety margin imposed in order to protect the integrity of the human organism under maximal effort. Perception of afferent input associated with effort leads to conscious or unconscious decisions to modulate or terminate performance; however, the underlying mechanisms of cerebral control are not fully understood. The idea to move borders of performance with the help of biochemicals is two millennia old. Biochemical findings resulted in highly effective substances widely used to increase performance in daily life, during preparation for sport events and during competition, but many of them must be considered as doping and therefore illegal. Supplements and food have ergogenic potential; however, numerous concepts are controversially discussed with respect to legality and particularly evidence in terms of usefulness and risks. The effect of evidence-based nutritional strategies on adaptations in terms of gene and protein expression that occur in skeletal muscle during and after exercise training sessions is widely unknown. Biochemical research is essential for better understanding of the basic mechanisms causing fatigue and the regulation of the dynamic adaptation to physical and mental training.


2010 ◽  
Vol 24 (3) ◽  
pp. 198-209 ◽  
Author(s):  
Yan Wang ◽  
Jianhui Wu ◽  
Shimin Fu ◽  
Yuejia Luo

In the present study, we used event-related potentials (ERPs) and behavioral measurements in a peripherally cued line-orientation discrimination task to investigate the underlying mechanisms of orienting and focusing in voluntary and involuntary attention conditions. Informative peripheral cue (75% valid) with long stimulus onset asynchrony (SOA) was used in the voluntary attention condition; uninformative peripheral cue (50% valid) with short SOA was used in the involuntary attention condition. Both orienting and focusing were affected by attention type. Results for attention orienting in the voluntary attention condition confirmed the “sensory gain control theory,” as attention enhanced the amplitude of the early ERP components, P1 and N1, without latency changes. In the involuntary attention condition, compared with invalid trials, targets in the valid trials elicited larger and later contralateral P1 components, and smaller and later contralateral N1 components. Furthermore, but only in the voluntary attention condition, targets in the valid trials elicited larger N2 and P3 components than in the invalid trials. Attention focusing in the involuntary attention condition resulted in larger P1 components elicited by targets in small-cue trials compared to large-cue trials, whereas in the voluntary attention condition, larger P1 components were elicited by targets in large-cue trials than in small-cue trials. There was no interaction between orienting and focusing. These results suggest that orienting and focusing of visual-spatial attention are deployed independently regardless of attention type. In addition, the present results provide evidence of dissociation between voluntary and involuntary attention during the same task.


2008 ◽  
Vol 24 (4) ◽  
pp. 218-225 ◽  
Author(s):  
Bertram Gawronski ◽  
Roland Deutsch ◽  
Etienne P. LeBel ◽  
Kurt R. Peters

Over the last decade, implicit measures of mental associations (e.g., Implicit Association Test, sequential priming) have become increasingly popular in many areas of psychological research. Even though successful applications provide preliminary support for the validity of these measures, their underlying mechanisms are still controversial. The present article addresses the role of a particular mechanism that is hypothesized to mediate the influence of activated associations on task performance in many implicit measures: response interference (RI). Based on a review of relevant evidence, we argue that RI effects in implicit measures depend on participants’ attention to association-relevant stimulus features, which in turn can influence the reliability and the construct validity of these measures. Drawing on a moderated-mediation model (MMM) of task performance in RI paradigms, we provide several suggestions on how to address these problems in research using implicit measures.


2015 ◽  
Vol 27 (4) ◽  
pp. 159-169 ◽  
Author(s):  
Elsbeth D. Asbeek Brusse ◽  
Marieke L. Fransen ◽  
Edith G. Smit

Abstract. This study examined the effects of disclosure messages in entertainment-education (E-E) on attitudes toward hearing protection and attitude toward the source. In addition, the (mediating) role of the underlying mechanisms (i.e., transportation, identification, and counterarguing) was studied. In an experiment (N = 336), three different disclosure messages were compared with a no-disclosure condition. The results show that more explicit disclosure messages negatively affect transportation and identification and stimulate the generation of counterarguments. In addition, the more explicit disclosure messages affect both attitude measures via two of these processes (i.e., transportation and counterarguing). Less explicit disclosure messages do not have this effect. Implications of the findings are discussed.


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