In vitro study of the neuropathic potential of the organophosphorus compounds fenamiphos and profenofos: Comparison with mipafox and paraoxon

Emerick, Guilherme Luz; Fernandes, Liliam; Paula, Eloísa Silva de; Barbosa, Fernando; Santos, Neife Aparecida Guinaim dos; Santos, Antônio Cardozo dos

doi:10.1016/j.tiv.2015.04.009

Cited by 12 publications

(12 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Maintaining Ca 2+ levels within physiological limits is a necessity since the increased influx of this ion constitutes an important mechanism of toxic cell death. In line with this, it has been widely documented that various organophosphate, pyrethroid, and carbamate pesticides, as well as rotenone, were able to significantly increase basal intracellular Ca 2+ levels [37,[39][40][41][42][43][44][45][46][47][48][49][50]. The main results of these studies are shown in Table 1.…”

Section: General Effects Of Pesticides On Ca 2+ Homeostasismentioning

confidence: 56%

“…In line with the above, it has been observed that several organophosphate pesticides were able to significantly increase calpain activity [39,41,50,65]. Calpain activation has been shown to be related to the degradation of cytoskeletal elements and axonal degeneration, a typical feature of organophosphate-induced toxicity [137][138][139][140].…”

Section: Effects On Ca 2+ Binding Proteins and Intracellular Signaling Pathwaysmentioning

confidence: 70%

“…Under conditions of moderate oxidative stress, calpain activation could exert a defensive function by enhancing the activation of PMCAs to remove excess of Ca 2+ from cytosol [64]. However, when oxidative stress is prolonged and/or severe, calpains can trigger the degradation of PMCAs and cellular cytoarchitectural elements, ultimately leading to apoptosis [39,41,64,185].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Systematic Review of Calcium Channels and Intracellular Calcium Signaling: Relevance to Pesticide Neurotoxicity

Costas-Ferreira

Faro

2021

IJMS

View full text Add to dashboard Cite

Pesticides of different chemical classes exert their toxic effects on the nervous system by acting on the different regulatory mechanisms of calcium (Ca2+) homeostasis. Pesticides have been shown to alter Ca2+ homeostasis, mainly by increasing its intracellular concentration above physiological levels. The pesticide-induced Ca2+ overload occurs through two main mechanisms: the entry of Ca2+ from the extracellular medium through the different types of Ca2+ channels present in the plasma membrane or its release into the cytoplasm from intracellular stocks, mainly from the endoplasmic reticulum. It has also been observed that intracellular increases in the Ca2+ concentrations are maintained over time, because pesticides inhibit the enzymes involved in reducing its levels. Thus, the alteration of Ca2+ levels can lead to the activation of various signaling pathways that generate oxidative stress, neuroinflammation and, finally, neuronal death. In this review, we also discuss some proposed strategies to counteract the detrimental effects of pesticides on Ca2+ homeostasis.

show abstract

Section: General Effects Of Pesticides On Ca 2+ Homeostasismentioning

confidence: 56%

Section: Effects On Ca 2+ Binding Proteins and Intracellular Signaling Pathwaysmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Systematic Review of Calcium Channels and Intracellular Calcium Signaling: Relevance to Pesticide Neurotoxicity

Costas-Ferreira

Faro

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…3), rat C6 glioma cells (Flaskos et al, 1998) and human SH-SY5Y cells (Chen et al, 2013) appears to be largely insensitive to TCP exposure. The underlying cause for the difference in sensitivity between different cell types is unclear, but it is unlikely to be due to the absence of traditional TCP targets such as NTE and AChE (Carrington and Abou-Donia, 1988), since even PC12, N2A, C6 and SH-SY5Y cells are all well known to express these proteins (Li and Casida, 1998;Hargreaves et al, 2006;Emerick et al, 2015). Earlier studies demonstrated that ToCP (most likely via CBDP) inhibits NTE and AChE at dose levels that convert to $10 mM (Carrington and Abou-Donia, 1988;Cohen et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

In vitro neurotoxic hazard characterization of different tricresyl phosphate (TCP) isomers and mixtures

et al. 2017

View full text Add to dashboard Cite

A B S T R A C TExposure to tricresyl phosphates (TCPs), via for example contaminated cabin air, has been associated with health effects including the so-called aerotoxic syndrome. While TCP neurotoxicity is mainly attributed to ortho-isomers like tri-ortho-cresyl phosphate (ToCP), recent exposure and risk assessments indicate that ToCP levels in cabin air are very low. However, the neurotoxic potential of non-ortho TCP isomers and TCP mixtures is largely unknown. We therefore measured effects of exposure (up to 48 h) to different TCP isomers, mixtures and the metabolite of ToCP (CBDP: cresyl saligenin phosphate) on cell viability and mitochondrial activity, spontaneous neuronal electrical activity, and neurite outgrowth in primary rat cortical neurons.The results demonstrate that exposure to TCPs (24-48 h, up to 10 mM) increases mitochondrial activity, without affecting cell viability. Effects of acute TCP exposure (30 min) on neuronal electrical activity are limited. However, electrical activity is markedly decreased for the majority of TCPs (10 mM) following 48 h exposure. Additional preliminary data indicate that exposure to TCPs (48 h, 10 mM) did not affect the number of neurites per cell or average neurite length, except for TmCP and the analytical TCP mixture (Sigma) that induced a reduction of average neurite length.The combined neurotoxicity data demonstrate that the different TCPs, including ToCP, are roughly equipotent and a clear structure-activity relation is not apparent for the studied endpoints. The noobserved-effect-concentrations (1 mM) are well above current exposure levels indicating limited neurotoxic health risk, although exposures may have been higher in the past. Moreover, prolonged and/or repeated exposure to TCPs may exacerbate the observed neurotoxic effects, which argues for additional research.

show abstract

“…Both were focused on OP acute cholinergic neurotoxicity; the first investigated the short term inhibition of AchE in spinal cells (Goldberg et al 1980), and the second performed electrophysiological and video recordings of muscle relaxation in co-culture with spinal motor neurons to evaluate the efficacy of AchE reactivation therapy (Drexler et al 2011). In the context of OPIDN, various efforts were reported as focusing towards the development of in vitro models that could help predict whether a particular OP is capable of causing OPIDN in humans (Emerick et al 2012; Fernandes et al 2015; Emerick et al 2015). Each of these studies used a neuroblastoma clonal cell line (SH-SY5Y) originally derived from a metastatic bone tumor, which exhibits only partial cholinergic features after differentiation.…”

Section: Cell and Animal Models To Study Opidn And Als: What Has Beenmentioning

confidence: 99%

Organophosphate neurotoxicity to the voluntary motor system on the trail of environment-caused amyotrophic lateral sclerosis: the known, the misknown, and the unknown

et al. 2017

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset paralytic disorder. It is characterized by progressive degeneration of the motor neurons controlling voluntary movement. The underlying mechanisms remain elusive, a fact that has precluded development of effective treatments. ALS presents as a sporadic condition 90–95% of the time, i.e. without familial history or obvious genetic mutation. This suggests that ALS has a strong environmental component. Organophosphates (OPs) are prime candidate neurotoxicants in the etiology of ALS, as exposure to OPs was linked to higher ALS incidence among farmers, soccer players, and Gulf War veterans. Also, polymorphisms in paraoxonase 1, an enzyme that detoxifies OPs, may increase individual vulnerability both to OP poisoning and to the risk of developing ALS. Furthermore, exposure to high doses of OPs can give rise to OP-induced delayed neuropathy (OPIDN), a debilitating condition akin to ALS characterized by similar motor impairment and paralysis. The question we pose in this review is: “what can we learn from acute exposure to high doses of neurotoxicants (OPIDN) that could help our understanding of chronic diseases resulting from potentially decades of silent exposure (ALS)?” The resemblances between OPIDN and ALS are striking at the clinical, etiological, neuropathological, cellular, and potentially molecular levels. Here, we critically present available evidence, discuss current limitations, and posit future research. In the search for the environmental origin of ALS, OPIDN offers an exciting trail to follow, which can hopefully lead to the development of novel strategies to prevent and cure these dreadful disorders.

show abstract

In vitro study of the neuropathic potential of the organophosphorus compounds fenamiphos and profenofos: Comparison with mipafox and paraoxon

Cited by 12 publications

References 55 publications

Systematic Review of Calcium Channels and Intracellular Calcium Signaling: Relevance to Pesticide Neurotoxicity

Systematic Review of Calcium Channels and Intracellular Calcium Signaling: Relevance to Pesticide Neurotoxicity

In vitro neurotoxic hazard characterization of different tricresyl phosphate (TCP) isomers and mixtures

Organophosphate neurotoxicity to the voluntary motor system on the trail of environment-caused amyotrophic lateral sclerosis: the known, the misknown, and the unknown

Contact Info

Product

Resources

About