Effects of acute chlorpyrifos exposure on in vivo acetylcholine accumulation in rat striatum

Karanth, Subramanya; Liu, Jing; Mirajkar, Nikita; Pope, Carey

doi:10.1016/j.taap.2006.04.006

Cited by 27 publications

(28 citation statements)

References 40 publications

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“…However, both in frontal cortex and striatum, at the peak of inhibition between 2 and 7 days after administration, the two higher doses achieved similar levels of AChE activity reduction. Similar results have previously been reported in striatum following acute sc CPF administration (Karanth et al, 2006). In this report, using in vivo microdialysis, authors found that the levels of ACh in rat striatum are higher at 4 and 7 days after dosing (84, 156 and 279 mg/kg of CPF, s.c.) than at day 1.…”

Section: Discussionsupporting

confidence: 89%

“…In contrast, Karanth et al (2006) have suggested that regions with higher cholinesterase specific activity, such as striatum, would take longer to recover normal activity following CPF exposure. However, we have found a strong inhibition in all the zones analyzed during the peak of inhibition, regardless of the densities of cholinesterases in the tissues.…”

Section: Discussionmentioning

confidence: 93%

“…As control we measured the inhibitory effect of CPF on AChE activity in the same brain areas. Most research in the field measured AChE activity in the whole brain or restricted brain regions (Betancourt et al, 2007;Karanth et al, 2006;Lee et al, 2011). Thus, there are few studies that have investigated the consequences of OPs on AChE regional activity (Perrier et al, 2005), although the relevance of brain regional activity for cholinergic and noncholinergic parameters involved as in mechanisms of toxicity of OPs has been pointed (Gupta, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Dose-dependent regional brain acetylcholinesterase and acylpeptide hydrolase inhibition without cell death after chlorpyrifos administration

et al. 2013

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-Organophosphates (OPs) are important toxic compounds commonly used for a variety of purposes in agriculture, industry and household settings. It has been well established that the main mechanism of acute toxic action of OP is the inhibition of acetylcholinesterase (AChE). However, we observed long term deficit after acute subcutaneous exposure to Chlorpyrifos (CPF) even when AChE activity is restored. In fact, besides AChE inhibition, non-AChE targets have also been proposed as an alternative mechanism involved in the acute lethal action and side effects of short or long-term exposure. In this context, our main aim in this research was to establish a dose-response curve of Acylpeptide hydrolase (APH) and AChE regional brain activity after acute CPF administration that could explain these long term effects observed in the literature. Moreover, since available data suggest that long term effects of OPs exposure could involve neuronal cell death, our second aim was to evaluate, assessing by Fluoro-Jade B (FJB) staining, whether CPF produces induced cell death. Our results show that an acute exposure to 250 mg/kg CPF does not induce neuronal death as measured by FJB but produces highest AChE regional brain inhibition after administration. In addition, APH seems to be more sensitive than AChE to CPF exposure because after 31 days of exposure, complete recovery was seen only for APH activity at Frontal Cortex, Cerebellum and Brain Stem.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Dose-dependent regional brain acetylcholinesterase and acylpeptide hydrolase inhibition without cell death after chlorpyrifos administration

et al. 2013

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“…Although, CPF has been shown to be relatively safe in adult animals, newly discovered evidence indicates that CPF is a developmental neurotoxicant in the fetus and is thus harmful (Garcia et al 2003). In animals and cellular models, chlorpyrifos inhibits neural cellular replication (Qian et al 2001), interferes with cellular differentiation (Crumpton et al 2000), evokes oxidative stress, alters neurotransmission (Dam et al 1999;Bloomquist et al 2002;Karanth et al 2006;Slotkin and Seidler, 2007) and induces neurobehavioral changes (Ricceri et al 2006). Additionally, animals exposed to CPF in utero or as juveniles display motor and cognitive delays (Moser 2000).…”

Section: Introductionmentioning

confidence: 99%

Characterization of chlorpyrifos-induced apoptosis in placental cells

Saulsbury¹,

Heyliger²,

Wang³

et al. 2008

Toxicology

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The mechanism by which chlorpyrifos exerts its toxicity in fetal and perinatal animals has yet to be elucidated. Since the placenta is responsible for transport of nutrients and is a major supplier hormones to the fetus, exposure to xenobiotics that alter the function or viability of placenta cells could ostensibly alter the development of the fetus. In this study, JAR cells were used to determine if CPF and the metabolites 3,5,6-trichloro-2-pyridinol (TCP) and chlorpyrifos-oxon (CPO) are toxic to the placenta. Our results indicate that chlorpyrifos (CPF), and its metabolite chlorpyrifos-oxon (CPO) caused a dose-dependent reduction in cellular viability with CPF being more toxic than its metabolites. Chlorpyrifos-induced toxicity was characterized by the loss of mitochondrial potential, the appearance of nuclear condensation and fragmentation, down-regulation of Bcl-2 as well as upregulation of TNFα and FAS mRNA. Pharmacological inhibition of FAS, nicotinic and TNF-α receptors did not attenuate CPF-induced toxicity. Atropine exhibited minimal ability to reverse toxicity. Furthermore, signal transduction inhibitors PD98059, SP600125, LY294002 and U0126 failed to attenuate toxicity; however, SB202190 (inhibitor of p38α and p38β MAPK) sensitized cells to CPF-induced toxicity. Pan-caspase inhibitor Q-VD-OPh produced a slight but significant reversal of CPF-induced toxicity indicating that the major caspase pathways are not integral to CPF-induced toxicity. Taken collectively, these results suggest that chlorpyrifos induces apoptosis in placental cells through pathways not dependent on FAS/TNF signaling, activation of caspases or inhibition of cholinesterase. In addition, our data further indicates that activation of p38 MAPK is integral to the protection cells against CPF-induced injury.

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“…After terminating the dialysis procedure, animals were sacrificed by decapitation using a guillotine, tissues were collected and both tissues and microdialysates were stored at −80 • C until analysis. Acetylcholine in the dialysis fractions was analyzed using high-performance liquid chromatography (HPLC) coupled to electrochemical detection using a Coulochem III detector (ESA, Chelmsford, MA) (Herzog et al, 2003;Karanth et al, 2006). An external standard curve was used to quantify acetylcholine in dialysates.…”

Section: Animals and Surgerymentioning

confidence: 99%

Comparative in vivo effects of parathion on striatal acetylcholine accumulation in adult and aged rats

et al. 2007

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Effects of acute chlorpyrifos exposure on in vivo acetylcholine accumulation in rat striatum

Cited by 27 publications

References 40 publications

Dose-dependent regional brain acetylcholinesterase and acylpeptide hydrolase inhibition without cell death after chlorpyrifos administration

Dose-dependent regional brain acetylcholinesterase and acylpeptide hydrolase inhibition without cell death after chlorpyrifos administration

Characterization of chlorpyrifos-induced apoptosis in placental cells

Comparative in vivo effects of parathion on striatal acetylcholine accumulation in adult and aged rats

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