Modulation of paraoxon toxicity by the cannabinoid receptor agonist WIN 55,212-2

Nallapaneni, Anuradha; Liu, Jing; Karanth, Subramanya; Pope, Carey

doi:10.1016/j.tox.2006.08.002

Cited by 29 publications

(39 citation statements)

References 47 publications

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“…146,147 Similar cholinergic toxicity and AChE inhibition have been observed after the acute treatment of chlorpyriphos in mice CB1(−/−) and the wild type. However, chlorpyrifos significantly reduces hippocampal ACh release ex vivo in both, but significantly more so in CB1(−/−).…”

Section: Long Term Cns Neurotoxicitymentioning

confidence: 57%

Neurotoxic Effects Associated with Current Uses of Organophosphorus Compounds

Mangas

Vilanova

Estévez

et al. 2016

Journal of the Brazilian Chemical Society

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Organophosphorus compounds (OPs) are a large and diverse class of chemicals that have been synthesized, since the XIX century for several purposes like chemical weapons, flame-retardants, ectoparasiticides and investigational new drugs, but mainly as agrochemicals in agriculture and indoor. Although the amount of OP pesticides being used is declining, especially in developed countries, OPs continue being one of the most important classes of insecticides and chemical warfare agents today due to its toxic effects on the enzyme acetylcholinesterase (AChE). Existing research on the toxicological effects of OPs is extensive, however, there is a lack of knowledge on the long-term effects of low levels of OPs and their exactly pathways of toxicity. Recent data prove that other molecular targets than AChE could be targeted by OPs, triggering these effects. Here these data are reviewed and it is highlighted that the current uses of OPs are producing several neurotoxic effects. It is also shown that, to protect people from possible uses and misuses of OPs, more regulations on OPs are needed. Moreover, more mechanistic studies are needed to completely understand their toxicological interactions and mechanisms of action and to identify the whole group of enzymes that interact with them.

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Section: Long Term Cns Neurotoxicitymentioning

confidence: 57%

Neurotoxic Effects Associated with Current Uses of Organophosphorus Compounds

Mangas

Vilanova

Estévez

et al. 2016

Journal of the Brazilian Chemical Society

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“…For example, activation of CB1 cannabinoid receptors blocks β-amyloid toxicity through events far downstream from the receptors rather than interfering directly with its actions [24]. Cannabinoids also protect neurons from adverse effects of organophosphate pesticides [34], actions which we have reproduced in the sea urchin embryo (Table 1). One possibility is that disparate agents converge on common final signaling pathways to offset the effects of toxicants that act through different originating mechanisms but that ultimately compromise these downstream functions.…”

Section: Discussionmentioning

confidence: 81%

Amyloid precursor protein 96–110 and β-amyloid 1–42 elicit developmental anomalies in sea urchin embryos and larvae that are alleviated by neurotransmitter analogs for acetylcholine, serotonin and cannabinoids

Buznikov

Nikitina

Seidler

et al. 2008

Neurotoxicology and Teratology

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Amyloid precursor protein (APP) is overexpressed in the developing brain and portions of its extracellular domain, especially amino acid residues 96-110, play an important role in neurite Correspondence: Dr. T.A. Slotkin, Dept. of Pharmacology & Cancer Biology, Box 3813 DUMC, Duke University Medical Center, Durham, NC 27710-3813, Tel (919) 681 8015, Fax (919) 684 8197, e-mail: t.slotkin@duke.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. outgrowth and neural cell differentiation. In the current study, we evaluated the developmental abnormalities caused by administration of exogenous APP 96-110 in sea urchin embryos and larvae, which, like the developing mammalian brain, utilize acetylcholine and other neurotransmitters as morphogens; effects were compared to those of β-amyloid 1-42 (Aβ42), the neurotoxic APP fragment contained within neurodegenerative plaques in Alzheimer's Disease. Although both peptides elicited dysmorphogenesis, Aβ42 was far more potent; in addition, whereas Aβ42 produced abnormalities at developmental stages ranging from early cleavage divisions to the late pluteus, APP 96-110 effects were restricted to the intermediate, mid-blastula stage. For both agents, anomalies were prevented or reduced by addition of lipid-permeable analogs of acetylcholine, serotonin or cannabinoids; physostigmine, a carbamate-derived cholinesterase inhibitor, was also effective. In contrast, agents that act on NMDA receptors (memantine) or α-adrenergic receptors (nicergoline), and that are therapeutic in Alzheimer's Disease, were themselves embryotoxic, as was tacrine, a cholinesterase inhibitor from a different chemical class than physostigmine. Protection was also provided by agents acting downstream from receptor-mediated events: increasing cyclic AMP with caffeine or isobutylmethylxanthine, or administering the antioxidant, α-tocopherol, were all partially effective. Our findings reinforce a role for APP in development and point to specific interactions with neurotransmitter systems that act as morphogens in developing sea urchins as well as in the mammalian brain. NIH Public Access

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“…Recent studies on organic phosphorus compounds have shown that these compounds act directly on fatty acid amide hydrolase and monoacylglycerol lipase responsible for the degradation of endocannabinoids (23). In one study, it has been indicated that WIN 55,212-2, CB agonist, modulates the effects of organic phosphorous insecticides (24). In other studies, CB2 activation has been emphasized to inhibit adenylate cyclase (25) and increase intracellular free Ca 2+ levels (26).…”

Section: Discussionmentioning

confidence: 99%

Cannabinoid receptor type 2 agonist JWH-133 deteriorates the liver toxicity induced by cypermethrin

2018

Turk J Vet Anim Sci

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IntroductionCYP is a synthetic type II pyrethroid insecticide widely used for the control of ectoparasites of domestic animals and home pest control owing to its high insecticidal potential and lower mammalian toxicity (1). CYP shows its effect via the voltage-dependent Na + and Ca 2+ channels in the membrane of nerve cells (2-4). There is an increasing amount of evidence suggesting toxic effects on nontarget organisms in chronic exposure of CYP (5,6). Several studies have shown that CYP causes oxidative stress, biochemical changes such as increase in activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH); elevation in levels of thiobarbituric acid reactive substances (TBARS), a decrease in activities of the antioxidant enzymes (7,8), and histopathological changes such as vacuolar degeneration, enlarged sinusoid, vacuole formation in hepatocytes, pleomorphism in the nucleus, congestion, necrosis, hepatocellular hypertrophy, multinucleated hepatocytes, mononuclear cell infiltration (MCI), and increase in Kupffer cell numbers (2,6).Marijuana or cannabis, whose main active ingredient is delta-9-tetrahydrocannabinol, activates two G proteincoupled membrane receptors, named CB1 and CB2 (9-11). CB1 is mainly expressed in the nervous system and is less expressed in various peripheral tissues such as the heart, gut, liver, and in cells such as endothelial cells and adipocytes. In comparison, CB2 is largely expressed in immune cells, tonsils, spleen, and testis. Moreover, it has been observed to be expressed to a lesser extent in other tissues and in cells like hepatic myofibroblasts (12).Recent studies have shown the dysregulation of endocannabinoid system in experimental models of bowel, liver, and heart diseases. Evidence suggests that Abstract: Cannabinoid receptor 2 (CB2) has a role in the pathology of some liver diseases. Cypermethrin (CYP) is a synthetic pyrethroid insecticide used commonly for the control of pests and vectors, and for protection of foodstuffs. In this study, the involvement of CB2 in CYP-induced liver damage in rats was investigated. CYP was applied to rats orally at a dose of 125 mg/kg bw per day for 14 days. CB2 agonist JWH-133 was administered by intraperitoneal injection at a dose of 3 mg/kg bw per day for the last 4 days of CYP toxicity. JWH-133 deteriorated the liver damage induced by CYP. JWH-133 increased serum hepatic enzyme activities (aspartate aminotransferase, alanine aminotransferase) in rats given CYP. However, it decreased lipid peroxidation. There were no differences in the levels of hepatic CB2 mRNA among the groups. CB2 receptors were expressed in a small amount in normal liver tissue. In contrast, the expression levels of CB2 in CYPtreated rats were increased in fibrocyte/fibroblast, bile duct epithelial cells, Kupffer cells, and mast cells. In conclusion, CB2 was upregulated in the liver exposed to CYP, predominantly in hepatic fibrogenic cells. JWH-133 enhanced the CYPinduced liver damage by receptor mediated and/or non...

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Modulation of paraoxon toxicity by the cannabinoid receptor agonist WIN 55,212-2

Cited by 29 publications

References 47 publications

Neurotoxic Effects Associated with Current Uses of Organophosphorus Compounds

Neurotoxic Effects Associated with Current Uses of Organophosphorus Compounds

Amyloid precursor protein 96–110 and β-amyloid 1–42 elicit developmental anomalies in sea urchin embryos and larvae that are alleviated by neurotransmitter analogs for acetylcholine, serotonin and cannabinoids

Cannabinoid receptor type 2 agonist JWH-133 deteriorates the liver toxicity induced by cypermethrin

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