Effect of cocaine, 95% oxygen and ellagic acid on the development and antioxidant status of cultured rat embryos.
Prenatal exposure to cocaine has been associated with adverse developmental effects and current data suggest cocaine induced malformations are caused by ischemic-reperfusion injury. This study was undertaken to assess a new in vitro model which uses a routine rat whole embryo culture system that incorporates a change in oxygen status, and to examine the effects of altered oxygen status and pretreatment with ellagic acid (EA), an anti-oxidant, after cocaine exposure. Embryos were evaluated by determining a developmental score and by measuring tissue reduced glutathione (GSH) levels. Following re-oxygenation with 95% O2 for the last 6 h of culture, embryos treated with cocaine had reduced developmental scores and GSH levels. Embryos treated with cocaine and not re-oxygenated with 95% O2 did not have reduced developmental scores. EA blocked the effects of cocaine on developmental score and GSH level. These data support ischemia-reperfusion injury as the mechanism of cocaine developmental toxicity.
Bohn
A A
AA
Department of Pathology, Colorado State University, Fort Collins 80523, USA.
Forsyth
C S
CS
Stoner
G D
GD
Reed
D J
DJ
Frank
A A
AA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003042:Cocaine / Q000633:toxicity*; D004610:Ellagic Acid / Q000494:pharmacology*; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D009924:Organ Culture Techniques; D010100:Oxygen / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000139:chemically induced; D014662:Vasoconstrictor Agents / Q000633:toxicity*
D000975:Antioxidants; D014662:Vasoconstrictor Agents; D004610:Ellagic Acid; D005978:Glutathione; D003042:Cocaine; D010100:Oxygen