JDB, Vol. 10, Pages 49: Organophosphate Insecticide Toxicity in Neural Development, Cognition, Behaviour and Degeneration: Insights from Zebrafish

Chlorpyrifos (CPF)CPF: 10 & 100 ng/mL-0–5 dpf-

increased impaired spatial discrimination

-

both decreased (10 ng/mL) and increased (100 ng/mL) response latency in adult zebrafish

[58]Chlorpyrifos (CPF)CPF: 100 ng/mL-0–5 dpf-

decreased swimming activity

[59]Malathion (MAL)MAL: 2.5 & 3 mg/L-3 hpf–5 dpf-

increased mortality

-

decreased hatching rates

-

decreased body length

-

and decreased surface area of eye.

[60]Malathion (MAL)MAL: 0.25, 0.5, 1, 3 & 5 mM-Adult (sexually mature)-

decreased Adenosine Di-Phosphate (ADP) and Adenosine Tri-Phosphate (ATP) levels

[61]Diazinon (DZN)DZN: 2000 & 3000 μg/L-8 hpf–96 hpf-

increased heart rate

-

increased mortality

-

increased morphological irregularities (axial and tail deformities, yolk sac/heart oedema, eye irregularities

-

reduced pigmentation

-

decreased hatching rate

[62]Chlorpyrifos (CPF)CPF: 0.25, 0.5, 0.75 & 1 mg/L-Acute: 5 dpf for 2 h
Sub-chronic: ≤1 hpf–11dpf-

Acute—increased (≥0.25 mg/L) and decreased (≥0.75 mg/L) locomotor activity.

-

Sub-chronic—increased behavioural irregularities

[63]Chlorpyrifos (CPF)CPF: 300, 1500 & 3000 nMRohon-Beard Development/Axonogenesis: agrin↓, cntn2↓, ntf3↓, sema3d↓3 hpf–27 hpf/51 hpf/72 hpf/4 dpf-

increased mortality

-

increased phenotypes (axial curvature, reduced body size and reduced pigmentation)

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decreased functioning AChE

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increased average chevron angle (somites)

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decreased HNK-1-positive cells

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decreased axonogenesis-related genes

[64]Chlorpyrifos (CPF)CPF: 0.29 μM-0–5 dpf-

significantly increased startle response

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increased transmitter turnover in larvae

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decreased dopamine/serotonin levels in adults

[65]Chlorpyrifos-oxon (CPF metabolite)CPF: 300 nM0.1 μg/L, 3 μg/L3 hpf–75 hpf-

Defective peripheral neuron development

[66]Dichlorvos (DCV)DCV: 20.81, 25 & 66.78 mg/L-0 hpf–96 hpf-

decreased hatching rates

-

increased pericardial oedema

-

increased spinal irregularities

-

decreased swimming activity

[67]Dichlorvos (DCV)

Phoxim (PHO)

DCV: N/A
PHO: 0.469, 0.513, 0.700 & 1.28 mg/L-Adult (sexually mature)-

DCV:

-

low toxicity (determined by LC50)

-

PHO:

-

intermediate and high levels of toxicity (determined by LC50)

[4]Chlorpyrifos (CPF)CPF: 0.6 μM-1 ypf for 24 h-

decreased swim rates

-

increased freeze response

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decreased AChE in muscle

[68]Chlorpyrifos (CPF)CPF: 0.01, 0.1 & 1 μM-6 hpf–24/48/72 hpf-

decreased functioning AChE

-

increased TCPy (trichloro-2-pyridinol)

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decreased functioning primary/secondary motor neurons, axonal growth and sensory neurons.

[69]Chlorpyrifos (CPF)

Diazinon (DZN)

Parathion (PA)

CPF: 0.3, 3 & 30 μM
DZN: 10 & 30 μM
PA: 10 & 30 μM-6 hpf–5 dpf-

Both CPF and DZN:

-

increased mortality

-

decreased functioning AChE

-

decreased locomotor activity

-

PA:

-

increased mortality

-

decreased functioning AChE

[70]Chlorpyrifos (CPF)CPF: 0.01 & 0.1 μM-0–7 dpf-

decreased swim speed

-

decreased anxiety-like behaviour

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increased behavioural irregularities

-

shortened body lengths and tail defects

[71]Monocrotophos (MCP)MCP: 0.001 & 0.100 mg/LSexual Differentiation: cyp19a1a↑, cyp19a1b↑, foxl2↑, dmrt1↓, B-actin, ef1-a72 hpfV–16 dpf-

increased proportion of females

-

alteration in expression of sexual differentiation genes

[72]Chlorpyrifos (CPF)
Dichlorvos (DCV)
Diazinon (DZN)CPF: 1, 10, 100 & 1000 μM
DCV: 100 & 1000 μM
DZN: 100 & 1000 μM-1 hpf–5 dpf-

CPF:

-

increased mortality

-

increased kyphosis

-

decreased spine length

-

increased spontaneous movement

-

and decreased heart rate

-

DCV:

-

increased mortality

-

increased spontaneous movement.

-

DZN:

-

increased mortality

-

increased pericardial oedema

[73]Chlorpyrifos (CPF)CPF: 30, 100 & 300 μg/LGfap, Mbp↓, Elavl3↑, Ngn1↑, Nestin↑, Shha↑0–5 dpf-

significantly decreased hatching rates

-

increased spine and yolk sac abnormalities

-

significantly decreased heart rates

-

significantly decreased swim speed/distance

[50]Chlorpyrifos (CPF)CPF: 200 & 400 μg/L-2 hpfV–72 hpf-

decreased AChE activity

-

increased AChE gene expression

-

increased glutathione (GSH) levels

[74]Dichlorvos (DCV)DCV: 6, 19, & 32 mg/LOxidative Stress: Nrf2 (many other associated genes within the Nrf2 pathway also examined)6–12 mpf-

decreased cholinesterase (ChE) levels in the heart/brain

-

increased myo-degeneration

-

increased testis degeneration

-

increased pancreas zymogen granule depletion

-

decreased glycogen in liver

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altered expression of genes involved in Nrf2 signalling

[75]Monocrotophos (MCP)MCP: 10, 20, 30, 40, 50 & 60 mg/L-4 hpf–96 hpf-

moderate toxicity (determined by LC50)

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decreased body length

-

decreased heart rate

-

decreased functioning AChE levels

[1]Monocrotophos (MCP)MCP: 100 μg/LHPI Axis: Crf, Gr↓, POMC↓, P45011β, 11B-HSD2, StAR, 20B-HSD2↑, MC2R↓, TAT, PEPCKAdult (sexually mature)—21 d exposure-

decreased whole-body cortisol

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increased/decreased hypothalamic-pituitary-inter-renal (HPI) axis associated genes

[76]Chlorpyrifos (CPF)CPF: 2 & 5 μM-Adult (sexually mature)-

increased oxidative stress

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decreased neurotransmitter metabolism

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increased energy exhaustion

[77]Chlorpyrifos (CPF)
Phoxim (PHO)CPF: 0.28- 13.03 mg/L
PHO: 0.89–26.48 mg/L-Embryo (1 hpf), larvae (72 hpf) and juvenile (1 mpf)—96 h exposure-

CPF was determined to be more toxic than PHO (determined by LC50)

[78]Diazinon (DZN)DZN: 6.5 mg/L-6 hpf–5 dpf-

Moderate toxicity (determined by LC50)

[2]Dichlorvos (DCV)DCV: 15 mg/L-Adult (sexually mature) 4–5 m—24 h exposure-

increased levels of malondialdehyde (MDA) in liver/kidney

-

increased glutathione (GSH) in liver/kidney/brain

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increased superoxide dismutase in liver

-

decreased levels of superoxide dismutase in brain

-

decreased catalase in kidney/brain.

[79]Malathion (MAL)MAL: 250, 500 & 1000 μg/LHPG Axis: vtg1, vtg2, era↑, erB1, erB2, cyp19a1a, cyp19a1b↑6 dpf–10 dpf-

low toxicity (determined by LC50)

-

upregulation of gene expression within the hypothalamic-pituitary-gonadal (HPG) axis

[80]Chlorpyrifos (CPF)
Diazinon (DZN)CPF: 1, 10, & 25 μM
DZN: 10 & 100 μM-6 hpf–102 hpf-

CPF:

-

increased mortality

-

decreased hatching rates

-

increased spinal lordosis

-

reduced activity

-

DZN:

-

increased mortality

-

increased pericardial oedema

-

decreased mitochondrial bioenergetics

[18]Monocrotophos (MCP)MCP: 0.125, 0.625 & 1.25 uL/L 24–72 hpf-

DNA damage observed in peripheral blood

[81]Phosalone (PSL)PSL: 86–505 μg/L-8 wpf–96 h exposure-

decreased functioning AChE

-

decreased carboxylesterase (CaE)

-

increased glutathione (GSH)

[82]Chlorpyrifos (CPF)CPF: 30, 100 & 300 μg/LOxidative stress: Mn-Sod↑/↓, Cu/Zn-Sod↓, Gpx↓, Cat↓, Ucp2↓, bc12, Cox1↓ Glycolysis/Lipid: Gk↓, HK1, Pk↓, Pepckc↓, Aco↓, CPt1↓, Ppar-A↓, Acc1↓, Srebp 1a↓, Ppar-y↓, Fas↓, Fabp6, Apo↓, Dgat↓, LDLR↓, HMGCR, Fabp5Adult (sexually mature)-

increased levels of gut mucus

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decreased y-Protobacteria in gut

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decreased oxidative stress genes in gut and liver

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and decreased glycolysis and lipid metabolism-related genes

[56]Chlorpyrifos (CPF)CPF: 30, 100 & 300 μg/LCardiovascular: Mef2c↓, Bmp4↓, VEGFR-2, JunB↑, Tbx2
Lipid: Ppar-a, Ppar-y↓, Srebp 1a, Acc1, Fas↓, Cpt1↓, Aco, Apo↓, Fabp5, Fabp6↓, Dgat↓, LDLR2 hpf–7 dpf-

decreased lipid accumulation in heart

-

decreased triglyceride and total cholesterol

-

increased cellular apoptosis of heart tissue

-

decreased lipid metabolism genes

[83]Diazinon (DZN)
Dichlorvos (DCV)
Malathion (MAL)
Parathion (PA)DZN: 0.1 & 100 μg/L
DCV: N/A
MAL: 100 μg/L
PA: 0.1 μg/LCholinergic: AChE↑/↓
Neurodegeneration: c-Fos, lingo-1b↑, grin-1b↓5 hpf–5 dpf-

DZN:

-

decreased swimming distance

-

decreased velocity

-

increase in AChE associated gene expression inhibited functioning AChe

-

increased carboxylesterase activity

-

DCV:

-

increased AChE associated genes.

-

MAL:

-

decreased swimming distance

-

decreased velocity

-

increase in AChE associated gene expression

-

increase in neurodegenerative associated gene expression

-

increased carboxylesterase activity

-

PA:

-

decrease in AChE associated gene expression

-

and decrease in neurodegenerative associated gene expression

[84]Dichlorvos (DCV)DCV: 1, 5 & 10 mg/L-1 hpf–7 dpf-

decreased body length

-

decreased heart rates

-

decreased surface area of eye

-

decreased escape responses

-

decreased speed

-

decreased mobile time

[85]Sumithion (SMT)SMT: 1 mg/L-Adult (sexually mature)—96h exposure-

increased blood glucose levels

-

increased frequency of micronucleus in erythrocytes

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increased erythrocyte cellular and nuclear abnormalities

[86]Chlorpyrifos (CPF)CPF: 1 & 3 μM-Adult (sexually mature) 6–8 m—2/5 w exposure-

increased anxiety related activity (Novel Tank Diving Test)

-

increased approach response in shoaling assay

-

increased predator avoidance activity (predator avoidance assay)

[87,88]Chlorpyrifos (CPF)
Malathion (MAL)
CPF: 0.019, 0.077, 0.31, 0.41, 1.01, 1.53 & 6.15 mg/L
MAL: 0.039, 0.16, 0.62, 2.90, 8.04, 8.54 & 12.45 mg/LOxidative Stress: Cat, CuSod, MnSod
Immunity: Cxcl↓, IL↑, Tnf↑/↓
Apoptosis: Cas8↑/↓, Cas9, P53, Bax
Endocrine: TRa, TRb↓, ERa, Tsh↓, Crh, cyp19a↑1 hpf–96 hpf-

Both CPF and MAL:

-

severe toxicity at larvae, juvenile and adult stages (compared to embryo stage)

-

significant changes in expression of immunity, apoptosis, and endocrine related genes

[57]Sumithion (SMT)SMT: 0.1, 0.2, 0.4, 0.8 & 1.6 mg/L-Embryo/larvae-

increased mortality in embryos and larvae

-

decreased hatching rates

-

increased morphological irregularities in embryos (damaged/underdeveloped and darkened yolk sac, broken chorion, and aberrant notochord formation)

-

increased morphological irregularities in larvae (yolk sac ulcerations/swelling and oedema, heart damage, lesion at caudal region, uninflated swim bladder, head malformation, jaw irregularities, and notochord abnormalities).

[89]Chlorpyrifos (CPF)CPF: 1μM-Adult (sexually mature)—5 w exposure-

decreased brain cholinesterase (ChE) activity

-

increased fleeing score.

(Hawkey, 2021)Diazinon (DZN)DZN: 0.4, 1.25 & 4.0 μM 5–120 hpf-

Changes in Mitochondrial oxygen utilization in the brain and testes

[90]Malathion (MAL)
Chlorpyrifos (CPF)MAL: 5, 50 ug/L
CPF: 0.1 & 3 ug/L 0–14 dpf-

increases in reactive oxygen species

-

induction of oxidative stress

[91]Chlorpyrifos (CPF) Caspase 3↓, Bcl-2↓, Adult—8–12 months old
14 day exposure-

Significantly elevated ROS levels

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Elevated Reactive nitrogen species levels in high CPF dosage groups

[92]

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