Chlorpyrifos induces apoptosis in human monocyte cell line U937

Nakadai, Ari; Li, Qing; Kawada, Tomoyuki

doi:10.1016/j.tox.2006.04.055

Cited by 83 publications

(47 citation statements)

References 20 publications

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“…It should be noted that Q-VD-OPh does not inhibit calpains (Yang et al 2004) and thus CPF-induced toxicity may be mediated via the activation of these serine proteases or other proteolytic processes. Nonetheless, these observations are consistent with the induction of apoptosis and corroborate earlier findings which indicated that CPF induces toxicity through apoptotic mechanisms (Caughlan et al 2004;Nakadai 2006) and only partially through activation of the caspase system (Nakadai 2006).…”

Section: Discussionsupporting

confidence: 92%

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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Section: Discussionsupporting

confidence: 92%

Characterization of chlorpyrifos-induced apoptosis in placental cells

Saulsbury¹,

Heyliger²,

Wang³

et al. 2008

Toxicology

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“…Consequently, the dysregulation of apoptosis leads to a variety of immune disorders, including immunodeficiency, tumorigenesis, allergies, and autoimmunity (Zhang et al, 2005). While several in vitro studies have been performed in order to identify chemically induced apoptosis in immunocytes (Nakadai et al, 2006;Li et al, 2007Li et al, , 2009Nohara et al, 2008), in vivo detection is difficult because of the rapid clearance of apoptotic cells by phagocytic cells (Savill, 1995a,b;Savill and Haslett, 1995;Kamath et al, 1997;Pryputniewicz et al, 1998). In this study, we attempt to develop a detection method of ex vivo environmental-or chemical-related thymic apoptosis using mouse primary thymocytes and a human acute T-cell leukemia cell line.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis in immunocytes induced by several types of pesticides

Fukuyama¹,

Tajima²,

Ueda³

et al. 2009

Journal of Immunotoxicology

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“…The results were in accordance with Krishnamoorthy et al (2007), who also observed lymphoid depletion in follicles, mild inter-follicular fibrosis, lack of cortico-medullary differentiation, and lymphocytolysis in bursa of Fabricius of birds. The CPF has been reported to induce fragmentation of DNA in immune cells of humans in vitro (Nakadai et al, 2006). In treatment groups, bursa of Fabricius and spleen showed fragmentation of the nucleus of lymphocytes that were not reported earlier in vivo.…”

Section: Discussionmentioning

confidence: 71%

“…It is primarily used to control pests invading grains, cotton, fruit, nut, and vegetable crops, as well as lawns and ornamental plants (Ambali et al, 2009). CPF is also used in treatment of livestock and poultry farms (Nakadai et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Immuno-pathologic effects of oral administration of chlorpyrifos in broiler chicks

Khan

Mahmood

et al. 2013

Journal of Immunotoxicology

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This study sought to assess if chlorpyrifos (CPF) induced immunotoxic effects in orally-treated day-old broiler chicks. Groups of chicks received per os CPF diluted in xylene at 5, 10, and 20 mg/kg body weight (CPF-5, CPF-10, and CPF-20) orally daily for 15 days. Xylene and control groups received xylene alone (1 ml/kg BW) and physiological saline, respectively. At various times during/after the exposure regimens, different immune end-points were analyzed in the birds. Humoral immunity was examined by assessing antibody responses to sheep red blood cells. Cell-mediated immunity was measured via lymphoproliferative responses to avian tuberculin. Leukocyte phagocytic ability was measured using a carbon clearance assay. Results showed that CPF administered to broiler chicks caused a dose-dependent decrease in humoral immunity, cell-mediated immunity, and phagocytic activity. Dose-and time-related pathological changes were observed in bursa of Fabricius, spleen, and thymus in treated birds. These changes were mild, moderate, and severe, respectively, in the 5, 10, and 20 mg/kg CPF groups. The Bursa of Fabricius in treated birds showed increased inter-follicular connective tissue proliferation, severe moderate cytoplasmic vacuolation, edema, and degenerative changes such as pyknosis and fragmentation of nuclei that depleted the follicles of lymphoid cells. In the spleen, disorganization of follicular patterns, severe congestion, cytoplasmic vacuolation, degenerative changes, and hyperplasia of reticular cells were noted. The thymus in treated birds exhibited congestion, hyper-cellularity, and a presence of immature monocytes in the medullary region, as well as myoid cell necrosis. Taken together, these studies clearly demonstrated that chlorpyrifos could induce immunotoxicities in broiler birds.

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Chlorpyrifos induces apoptosis in human monocyte cell line U937

Cited by 83 publications

References 20 publications

Characterization of chlorpyrifos-induced apoptosis in placental cells

Characterization of chlorpyrifos-induced apoptosis in placental cells

Apoptosis in immunocytes induced by several types of pesticides

Immuno-pathologic effects of oral administration of chlorpyrifos in broiler chicks

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