Amelioration of ethanol-induced growth retardation by all-trans-retinoic acid and alpha-tocopherol in shell-less culture of the chick embryo.
The mechanisms of teratogenic action of ethanol (EtOH) were investigated by testing the hypothesis that all-trans-retinoic acid and/or alpha-tocopherol ameliorates ethanol-induced embryonic growth retardation. Chicken embryos were explanted in shell-less cultures and a single dose of EtOH (15, 30, or 50%) or 50% EtOH with either all-trans-retinoic acid (10(-8)M) or alpha-tocopherol (0.05 M) or a mix of all-trans-retinoic acid (10(-8)M) and alpha-tocopherol (0.05 M) was applied to the center of the blastodisc. EtOH significantly increased the mortality rate and induced growth retardation in a dose-dependent manner. In addition, EtOH increased malondialdehyde (MDA) levels, an indicator of oxidative stress and cell damage, in a dose dependent manner. All-trans-retinoic acid, the active form of Vitamin A, and/or alpha-tocopherol, an antioxidant, co-treatment with EtOH significantly diminished both the EtOH-induced mortality and growth retardation. However, only alpha-tocopherol co-treatment reduced the MDA levels. Thus, the mechanisms of teratogenic action of EtOH appear to involve initiation of oxidative stress as well as perturbation of retinoic acid (RA) signaling. It also appears likely that these mechanisms work independently of each other.
Satiroglu-Tufan
N Lale
NL
Department of Medical Biology, School of Medicine, Pamukkale University, Denizli, Turkey.
Tufan
A Cevik
AC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D046149:Embryo Culture Techniques; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005317:Fetal Growth Retardation / Q000139:chemically induced* / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D013723:Teratogens; D014212:Tretinoin / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D013723:Teratogens; D014810:Vitamin E; D000431:Ethanol; D008315:Malondialdehyde; D014212:Tretinoin