Protection by acetylsalicylic acid against hyperglycemia-induced glycation and neural tube defects in cultured early somite mouse embryos.
The embryopathic effects of hyperglycemia have been established in rodent embryos maintained in whole embryo culture during neurulation. This study addressed the possibility that the hyperglycemia-mediated teratogenic effects are associated with increased concentrations of glycated embryonic protein. Early somite mouse embryos were cultured in 50 mmol/l glucose for 48 h and subsequently demonstrated growth retardation and severe neural malformations. Incubation with 0.005 mmol/l acetylsalicylic acid, an effective anti-glycation agent, was partially protective against hyperglycemia-induced growth retardation, neural tube defects as well as the deleterious effects on the morphological development of specific tissues. Furosine measurements indicated that acetylsalicylic acid reduced individual embryonic concentrations of glycated protein in both hyperglycemic and normoglycemic embryos. Also, the total morphological score, somite number, head length and the forebrain morphological rating of individual embryos were negatively correlated with their tissue furosine content. The results indicate the possibility that hyperglycemia during embryo culture causes dysmorphogenesis via enhanced production of glycated embryonic proteins and that the protective action of acetylsalicylic acid could be mediated by its anti-glycation properties.
Kubow
S
S
School of Dietetics and Human Nutrition, Macdonald Campus of McGill University, Anne de Bellevue, PQ, Canada.
Yaylayan
V
V
Mandeville
S
S
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005947:Glucose / Q000633:toxicity*; D006031:Glycosylation / Q000187:drug effects; D006943:Hyperglycemia; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009436:Neural Tube Defects / Q000517:prevention & control*; D009924:Organ Culture Techniques
D005947:Glucose; D001241:Aspirin