An in vivo animal study assessing long-term changes in hypothalamic cytokines following perinatal exposure to a chemical mixture based on Arctic maternal body burdenReportar como inadecuado




An in vivo animal study assessing long-term changes in hypothalamic cytokines following perinatal exposure to a chemical mixture based on Arctic maternal body burden - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Environmental Health

, 10:65

First Online: 11 July 2011Received: 16 November 2010Accepted: 11 July 2011DOI: 10.1186-1476-069X-10-65

Cite this article as: Hayley, S., Mangano, E., Crowe, G. et al. Environ Health 2011 10: 65. doi:10.1186-1476-069X-10-65

Abstract

BackgroundThe geographic distribution of environmental toxins is generally not uniform, with certain northern regions showing a particularly high concentration of pesticides, heavy metals and persistent organic pollutants. For instance, Northern Canadians are exposed to high levels of persistent organic pollutants like polychlorinated biphenyls PCB, organochlorine pesticides OCs and methylmercury MeHg, primarily through country foods. Previous studies have reported associations between neuronal pathology and exposure to such toxins. The present investigation assessed whether perinatal exposure gestation and lactation of rats to a chemical mixture 27 constituents comprised of PCBs, OCs and MeHg based on Arctic maternal exposure profiles at concentrations near human exposure levels, would affect brain levels of several inflammatory cytokines

MethodsRats were dosed during gestation and lactation and cytokine levels were measured in the brains of offspring at five months of age. Hypothalamic cytokine protein levels were measured with a suspension-based array system and differences were determined using ANOVA and post hoc statistical tests.

ResultsThe early life PCB treatment alone significantly elevated hypothalamic interleukin-6 IL-6 levels in rats at five months of age to a degree comparable to that of the entire chemical mixture. Similarly, the full mixture and to a lesser degree PCBs alone elevated levels of the pro-inflammatory cytokine, IL-1b, as well as the anti-inflammatory cytokine, IL-10. The full mixture of chemicals also moderately increased in an additive fashion hypothalamic levels of the pro-inflammatory cytokines, IL-12 and tumor necrosis factor TNF-α. Challenge with bacterial endotoxin at adulthood generally increased hypothalamic levels to such a degree that differences between the perinatally treated chemical groups were no longer detectable.

ConclusionsThese data suggest that exposure at critical neurodevelopmental times to environmental chemicals at concentrations and combinations reflective of those observed in vulnerable population can have enduring consequences upon cytokines that are thought to contribute to a range of pathological states. In particular, such protracted alterations in the cytokine balance within the hypothalamus would be expected to favor marked changes in neuro-immune and hormonal communication that could have profound behavioral consequences.

List of AbbreviationsPCBpolychlorinated biphenyls

OCorganochloride pesticide

MeHgmethylmercury

IL-6interleukin-6

TNF-αtumor necrosis factor-α

CNScentral nervous system

LPSlipopolysaccharide

GD0gestation day 0

PNDpostnatal day

Electronic supplementary materialThe online version of this article doi:10.1186-1476-069X-10-65 contains supplementary material, which is available to authorized users.

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Autor: Shawn Hayley - Emily Mangano - Geoffrey Crowe - Nanqin Li - Wayne J Bowers

Fuente: https://link.springer.com/







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