Juvenile hormone synthesis and signaling disruption triggering male offspring induction and population decline in cladocerans (water flea): Review and adverse outcome pathway development

With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches. We first investigated the effect of a single administration of CDs on mouse airways. We showed that CDs induce an acute lung inflammation and identified airway macrophages as target cells of CDs. Then, we studied the cellular responses induced by CDs in an in vitro model of macrophages. We observed that CDs are internalized by these cells (molecular initial event) and induce a series of key events, including loss of lysosomal integrity and mitochondrial disruption (organelle responses), as well as oxidative stress, inflammasome activation, inflammatory cytokine upregulation and macrophage death (cellular responses). All these effects triggering lung inflammation as tissular response may lead to acute lung injury.

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The effects of gene × environment interactions on silver nanoparticle toxicity in the respiratory system: An adverse outcome pathway

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology ◽

10.1002/wnan.1708 ◽

2021 ◽

Author(s):

Tyler P. Nicholas ◽

William K. Boyes ◽

David K. Scoville ◽

Tomomi W. Workman ◽

Terrance J. Kavanagh ◽

...

Keyword(s):

Respiratory System ◽

Silver Nanoparticle ◽

Adverse Outcome ◽

Adverse Outcome Pathway ◽

Nanoparticle Toxicity ◽

Gene Environment

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Development changes in juvenile hormone and juvenile hormone acid titers in the hemolymph and in-vitro juvenile hormone synthesis by corpora allata of the silkworm, Bombyx mori

Journal of Insect Physiology ◽

10.1016/s0022-1910(97)00021-8 ◽

1997 ◽

Vol 43 (9) ◽

pp. 875-884 ◽

Cited By ~ 78

Author(s):

Shinya Niimi ◽

Sho Sakurai

Keyword(s):

Juvenile Hormone ◽

Bombyx Mori ◽

Corpora Allata ◽

Hormone Synthesis ◽

Silkworm Bombyx Mori

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Development of an Adverse Outcome Pathway for the Onset of Hypertension by Oxidative Stress-Mediated Perturbation of Endothelial Nitric Oxide Bioavailability

Applied In Vitro Toxicology ◽

10.1089/aivt.2016.0031 ◽

2017 ◽

Vol 3 (1) ◽

pp. 131-148 ◽

Cited By ~ 7

Author(s):

Frazer J. Lowe ◽

Karsta Luettich ◽

Marja Talikka ◽

Vy Hoang ◽

Linsey E. Haswell ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Adverse Outcome ◽

Adverse Outcome Pathway ◽

Endothelial Nitric Oxide ◽

Nitric Oxide Bioavailability

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Internal exposure dynamics drive the Adverse Outcome Pathways of synthetic glucocorticoids in fish

Scientific Reports ◽

10.1038/srep21978 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 33

Author(s):

Luigi Margiotta-Casaluci ◽

Stewart F. Owen ◽

Belinda Huerta ◽

Sara Rodríguez-Mozaz ◽

Subramanian Kugathas ◽

...

Keyword(s):

Predictive Power ◽

Adverse Outcome ◽

Plasma Concentrations ◽

Internal Exposure ◽

Adverse Outcome Pathway ◽

Conceptual Tool ◽

Fish Model ◽

Species Specific

Abstract The Adverse Outcome Pathway (AOP) framework represents a valuable conceptual tool to systematically integrate existing toxicological knowledge from a mechanistic perspective to facilitate predictions of chemical-induced effects across species. However, its application for decision-making requires the transition from qualitative to quantitative AOP (qAOP). Here we used a fish model and the synthetic glucocorticoid beclomethasone dipropionate (BDP) to investigate the role of chemical-specific properties, pharmacokinetics, and internal exposure dynamics in the development of qAOPs. We generated a qAOP network based on drug plasma concentrations and focused on immunodepression, skin androgenisation, disruption of gluconeogenesis and reproductive performance. We showed that internal exposure dynamics and chemical-specific properties influence the development of qAOPs and their predictive power. Comparing the effects of two different glucocorticoids, we highlight how relatively similar in vitro hazard-based indicators can lead to different in vivo risk. This discrepancy can be predicted by their different uptake potential, pharmacokinetic (PK) and pharmacodynamic (PD) profiles. We recommend that the development phase of qAOPs should include the application of species-specific uptake and physiologically-based PK/PD models. This integration will significantly enhance the predictive power, enabling a more accurate assessment of the risk and the reliable transferability of qAOPs across chemicals.

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