Inhibition of Serum Esterases in Juvenile Rats Repeatedly Exposed to Low Levels of Chlorpyrifos.
Inhibition of Serum Esterases in Juvenile Rats Repeatedly Exposed to Low Levels of Chlorpyrifos.
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DOI：
10.15226/2572-3162/5/1/00133
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Carr RL
中科院分区：
文献类型：
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作者：
Mosier JA;Hybart RL;Lewis AM;Alugubelly N;Mohammed AN;Carr RL
毒死蜱（CPF）是一种有机磷杀虫剂，已获得显着的关注线索与发育暴露的毒性报告。虽然CPF的典型毒性机制涉及脑乙酰胆碱酯酶（AChE）的抑制，我们已经报道，暴露的幼年大鼠的CPF水平，不产生任何抑制脑AChE的结果在以后的年龄在神经行为的改变。然而，目前尚不清楚暴露于这些低水平的CPF对血液酯酶活性的影响，血液酯酶活性不仅经常用作暴露的生物标志物，而且还用于确定风险评估中的暴露水平。为了确定这一点，雄性和雌性大鼠幼仔从出生后第10天至第16天经口暴露于玉米油（溶剂）或0.5、0.75或1.0 mg/kg CPF。末次染毒后12 h，测定血清胆碱酯酶（ChE）、丁酰胆碱酯酶（BChE）、羧酸酯酶（CES）、红细胞（RBC）和脑AChE活性。在所有酶的对照组或单独处理组中，性别之间没有差异。只有最高剂量1.0 mg/kg CPF产生显著的脑AChE抑制（22-24%），但所有剂量均显著抑制血液酯酶，其中血清CES（65-85%）的抑制作用最高，其次是血清BChE（57-76%），RBC AChE（35-65%），然后是血清ChE（16-32%）。我们的数据证实，血液酯酶抑制剂量的CPF，改变神经行为的表现，在没有影响脑乙酰胆碱酯酶活性。
Chlorpyrifos (CPF) is an organophosphorus insecticide that has gained significant attention cue to the reported toxicity associated with developmental exposure. While the canonical mechanism of toxicity of CPF involves the inhibition of brain acetylcholinesterase (AChE), we have reported that exposure of juvenile rats to levels of CPF that do not yield any inhibition of brain AChE results in neurobehavioral alterations at later ages. However, it is unclear what effect exposure to these low levels of CPF has on blood esterase activities which are frequently used not only as biomarkers of exposure but also to set exposure levels in risk assessment. To determine this, male and female rat pups were exposed orally from postnatal day 10 to 16 to either corn oil (vehicle) or 0.5, 0.75, or 1.0 mg/kg CPF. At 12 h after the final exposure, serum cholinesterase (ChE), butyrylcholinesterase (BChE), and carboxylesterase (CES), and red blood cell (RBC) and brain AChE activities were determined. There were no differences between sexes in either the controls or individual treatments for all enzymes. Only the highest dosage of 1.0 mg/kg CPF yielded significant brain AChE inhibition (22–24%) but all dosages significantly inhibited the blood esterases with inhibition being highest with serum CES (65–85%) followed by serum BChE (57–76%), RBC AChE (35–65%), and then serum ChE (16–32%). Our data verify that blood esterases are inhibited at dosages of CPF that alter neurobehavioral performance in the absence of effects on brain AChE activity.