Age-Dependent Acrylamide Neurotoxicity in Mice: Morphology, Physiology, and Function

Ko, Miau-Hwa; Chen, Wen-Pin; Lin-Shiau, Shoei-Yin; Hsieh, Sung‐Tsang

doi:10.1006/exnr.1999.7102

Cited by 54 publications

(52 citation statements)

References 34 publications

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“…For chemically related agents like vinyl chloride, a higher sensitivity of young individuals has been found in animals [38]. The neurotoxicity of acrylamide is also higher in the young compared to older animals [39]. Exposing young humans to these amounts of acrylamide during breast-feeding seems to be unacceptable.…”

Section: Resultsmentioning

confidence: 99%

Acrylamide: Increased Concentrations in Homemade Food and First Evidence of Its Variable Absorption from Food, Variable Metabolism and Placental and Breast Milk Transfer in Humans

et al. 2002

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We have developed a liquid chromatography/mass spectrometry (LC-MS/MS) assay to determine acrylamide in various body fluids. The assay also allows the reliable quantitation of acrylamide in food. In a total of 11 healthy male and female subjects, we were able to show that acrylamide from food given to humans is in fact absorbed from the gut. The half-lives determined in two male subjects were 2.2 and 7 h. Acrylamide was found in human breast milk and penetrated the human placenta (n = 3). The variability of acrylamide concentrations found in this investigation is most likely caused by variable intersubject bioavailability and metabolism. This may be an important indication that the assessment of the risk from acrylamide for the individual may be very difficult without knowing the concentrations of acrylamide in the body. This should be considered in the design of any risk assessment study or post hoc analysis of earlier studies. At this time, we suggest that pregnant women and breast-feeding mothers avoid acrylamide-containing food.

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Section: Resultsmentioning

confidence: 99%

Acrylamide: Increased Concentrations in Homemade Food and First Evidence of Its Variable Absorption from Food, Variable Metabolism and Placental and Breast Milk Transfer in Humans

et al. 2002

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“…13,14 The experimental procedure was approved by the Animal Care and Use Committee of the Johns Hopkins University. All procedures were conducted in 6-to 8-week-old female Sprague-Dawley rats weighing 70 to 80gm at the beginning of the study.…”

Section: Acrylamide Axonopathy Modelmentioning

confidence: 99%

“…Skin innervation was assessed by PGP 9.5 immunohistochemistry according to published protocols. 13 Changes in motor innervation were assessed by examining the innervated neuromuscular junction density in the intrinsic foot muscles using ␣-bungaratoxin binding. 17 Statistical analysis was done using ANOVA as described above.…”

Section: Acrylamide Axonopathy Modelmentioning

confidence: 99%

A novel endogenous erythropoietin mediated pathway prevents axonal degeneration

Keswani

Buldanlioglu

Fischer

et al. 2004

Annals of Neurology

143

116

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Clinically relevant peripheral neuropathies (such as diabetic and human immunodeficiency virus sensory neuropathies) are characterized by distal axonal degeneration, rather than neuronal death. Here, we describe a novel, endogenous pathway that prevents axonal degeneration. We show that in response to axonal injury, periaxonal Schwann cells release erythropoietin (EPO), which via EPO receptor binding on neurons, prevents axonal degeneration. We demonstrate that the relevant axonal injury signal that stimulates EPO production from surrounding glial cells is nitric oxide. In addition, we show that this endogenous pathway can be therapeutically exploited by administering exogenous EPO. In an animal model of distal axonopathy, systemic EPO administration prevents axonal degeneration, and this is associated with a reduction in limb weakness and neuropathic pain behavior. Our in vivo and in vitro data suggest that EPO prevents axonal degeneration and therefore may be therapeutically useful in a wide variety of human neurological diseases characterized by axonopathy.

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“…Regarding age-related susceptibility to ACR-induced toxicity, data from animal studies are insufficient and the findings are inconsistent (Kaplan and Murphy, 1972;Ko et al, 1999). Placental transfer of ACR has been reported in experimental animals and humans, and the fetal internal level of ACR on a weight-adjusted basis was estimated to be at least equal to that of human mothers (Ikeda et al, 1983;Schettgen et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Pathological assessment of the nervous and male reproductive systems of rat offspring exposed maternally to acrylamide during the gestation and lactation periods - a preliminary study

et al. 2008

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-To evaluate the developmental effects of exposure to acrylamide (ACR) on the nervous and male reproductive systems, pregnant Sprague-Dawley rats were given ACR at 0, 50, 100 or 200 ppm in the drinking water from gestational day 10 to postnatal day 21 and histopathological assessment of offspring was performed at weaning and postnatal week 11. Neurotoxicity was quantitatively assessed with reference to nerve fiber density, percentages of degenerated and small caliber axons in the sciatic nerves, and numbers of aberrant dot-like structures immunoreactive for synaptophysin in the cerebellar molecular layer. Although maternal neurotoxicity was evident from 100 ppm, no changes suggestive of neurotoxicity or testicular toxicity were observed in offspring. However, lowering of body weights was dose-dependently observed from birth at the dose levels of ≥50 ppm in males and ≥100 ppm in females. Maternal malnutrition was apparent at ≥100 ppm during the lactation period. Therefore, poor lactational ACR-exposure due to maternal toxicity might account for the lack of ACR-induced offspring toxicity other than retarded body growth.

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Age-Dependent Acrylamide Neurotoxicity in Mice: Morphology, Physiology, and Function

Cited by 54 publications

References 34 publications

Acrylamide: Increased Concentrations in Homemade Food and First Evidence of Its Variable Absorption from Food, Variable Metabolism and Placental and Breast Milk Transfer in Humans

Acrylamide: Increased Concentrations in Homemade Food and First Evidence of Its Variable Absorption from Food, Variable Metabolism and Placental and Breast Milk Transfer in Humans

A novel endogenous erythropoietin mediated pathway prevents axonal degeneration

Pathological assessment of the nervous and male reproductive systems of rat offspring exposed maternally to acrylamide during the gestation and lactation periods - a preliminary study

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