Effects of chronic prenatal ethanol exposure on mitochondrial glutathione and 8-iso-prostaglandin F2alpha concentrations in the hippocampus of the perinatal guinea pig.
It is hypothesised that oxidative stress is a key mechanism of ethanol neurobehavioural teratogenicity, resulting in altered endogenous antioxidant status and increased membrane lipid peroxidation in the hippocampus of chronic prenatal ethanol exposure (CPEE) offspring. To test this hypothesis, timed pregnant guinea-pigs (term, approximately gestational day (GD) 68) received chronic daily oral administration of (i) 4 g ethanol kg(-1) maternal bodyweight, (ii) isocaloric sucrose with pair feeding, or (iii) water. At GD 65 (term fetus) and postnatal day (PD) 0 (neonate), individual offspring were killed, the brain was excised and the hippocampi were dissected. Glutathione (GSH) concentration was measured in the cytosolic and mitochondrial fractions of hippocampal homogenate. The occurrence of lipid peroxidation was determined by measuring the concentration of 8-iso-prostaglandin F2+/- (8-iso-PGF2+/-). There was CPEE-induced decreased brain weight and hippocampal weight at GD 65 and PD 0, decreased mitochondrial GSH concentration in the hippocampus at PD 0, with no change in mitochondrial GSH concentration at GD 65 or cytosolic GSH concentration at GD 65 or PD 0, and no change in mitochondrial or whole-homogenate 8-iso-PGF2+/- concentration in the hippocampus at GD 65 or PD 0. The data demonstrate that CPEE produces selective mitochondrial dysfunction in the hippocampus of the neonatal guinea-pig, involving GSH depletion.
Green
C R
CR
Department of Pharmacology and Toxicology, Queen's University, Kingston, ON K7L 3N6, Canada.
Watts
L T
LT
Kobus
S M
SM
Henderson
G I
GI
Reynolds
J N
JN
Brien
J F
JF
D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight; D003600:Cytosol / Q000737:chemistry; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000032:analysis; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D020567:Fetal Weight; D005865:Gestational Age; D005978:Glutathione / Q000032:analysis*; D006168:Guinea Pigs; D006624:Hippocampus / Q000196:embryology / Q000648:ultrastructure*; D008431:Maternal-Fetal Exchange; D008928:Mitochondria / Q000737:chemistry*; D009929:Organ Size; D011247:Pregnancy
C075750:8-epi-prostaglandin F2alpha; D000431:Ethanol; D015237:Dinoprost; D005978:Glutathione