Prenatal cocaine administration increases glutathione and alpha-tocopherol oxidation in fetal rat brain.
Recent findings suggest that prenatal cocaine exposure results in significant attenuation of uterine and placental blood flow. The extent of blood flow reduction to fetuses positively correlates with reductions in glial-derived neurotrophic factor (GDNF) and dopamine (DA). However, whether such changes in uterine blood flow are sufficient to induce oxidative stress have yet to be determined. In the following experiments, the impact of prenatal cocaine exposure on fetal brain levels of the endogenous antioxidant glutathione (GSH and its oxidized form GSSG) or the exogenous antioxidant alpha-tocopherol (alpha-T and its oxidized quinone form) was investigated. It was hypothesized that cocaine exposure would result in greater oxidation of both GSH and alpha-T. Results indicated that a single injection of cocaine to a drug-naive pregnant dam results in significant (-16.38%) reductions in the levels of GSH. GSSG can be either raised or reduced as a result of fetal uterine position: fetuses at the ovarian extremes show significant increases in GSSG in response to cocaine (+64.73%), whereas cervically situated fetuses show decreased GSSG (-47.91%). Additionally, cocaine significantly decreased the levels of alpha-T (-15.9%) and increased the levels of its oxidative product alpha-Tquinone (alpha-Tq, +34.05%). Levels of alpha-T were not affected by fetal uterine position. These data collectively suggest that cocaine exposure increases the utilization of both endogenous and exogenous anti-oxidants in the fetal rat brain. Along with previous studies, these data support the hypothesis that cocaine-induced vasoconstriction results in oxidative stress in the gestating fetus.
Lipton
Jack W
JW
Department of Neurological Sciences, Rush University, Rush-Presbyterian-St. Luke's Medical Center, 2242 W. Harrison Street, Suite 265, Chicago, IL 60612, USA. jlipton@rush.edu
Gyawali
Sandeep
S
Borys
Ewa D
ED
Koprich
James B
JB
Ptaszny
Magdalena
M
McGuire
Susan O
SO
D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D003042:Cocaine / Q000633:toxicity*; D004032:Diet; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D008098:Litter Size / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D010084:Oxidation-Reduction; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012744:Sex Ratio; D014599:Uterus / Q000033:anatomy & histology; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000378:metabolism*; D014811:Vitamin E Deficiency / Q000378:metabolism
D009419:Nerve Tissue Proteins; D014810:Vitamin E; C002421:tocopherylquinone; D005978:Glutathione; D003042:Cocaine