Editor’s Highlight: Ethylene Glycol Teratogenicity: A Role for Embryonic Acidosis?
| Autor: | Helen E. Ritchie, William S. Webster, Nigel P. Moore |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Ethylene Glycol Metabolite Embryonic Development Gestational Age In Vitro Techniques Toxicology Rats Sprague-Dawley Andrology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Heart Rate medicine Animals Incubation Acidosis Monocarboxylate transporter Embryonic heart biology Chemistry Hydrogen-Ion Concentration Culture Media Glycolates Rats Lactic acid Chorioallantoic membrane 030104 developmental biology Toxicity biology.protein Teratogenesis medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Toxicological Sciences. 161:421-430 |
| ISSN: | 1096-0929 1096-6080 |
| Popis: | Ethylene glycol (EG) is a developmental toxicant in pregnant rats and mice. A suggested mechanism for this toxicity is that the EG metabolite, glycolic acid (GA), causes acidosis which may affect the embryonic heart rate (HR). This inhibition would cause periods of embryonic bradycardia and arrhythmia resulting in increased embryonic death and malformation in surviving embryos. This hypothesis was investigated using gestational day (GD) 11 and 13 rat embryos in vitro. Increasing concentrations of GA or lactic acid in the incubation medium caused a decrease in external pH (pHe) and a concentration-dependent decrease in embryonic HR. Increased concentrations of GA or lactic acid with pHe corrected to normal levels did not affect HR. Severely decreased pHe, caused by reduced NaHCO3 in the incubation medium, had little effect on the HR of GD 13 embryos but substantially reduced the HR of GD 11 embryos. These results suggest that increased monocarboxylate concentration (glycolate or lactate) needs to be in combination with increased H+ concentration (low pHe) to influence the embryonic HR. These results implicate the monocarboxylate transporter reported to be present in the early postnatal rat heart, the chick embryonic heart throughout development, and the chorioallantoic placenta. The results showed some evidence that the adverse effect of GA and reduced pHe on the embryonic HR increased with duration of exposure and hence lends support to the suggested mechanism of embryotoxicity for EG. |
| Databáze: | OpenAIRE |
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