Alterations of brain tissue in fetal rats exposed to nicotine in utero: possible involvement of nitric oxide and catecholamines.
Histopathological changes in the brains of embryos from female rats treated with nicotine during pregnancy and possible involvement of nitric oxide (NO) and catecholamines in the nicotine-induced abnormalities of developing brain were investigated. Sexually mature female Wistar rats were given 1, 2, and 3 mg/kg nicotine hydrogen tartrate (NHT) subcutaneously for 20 days after mating. Levels of cotinine, a nicotine metabolite, in the maternal plasma increased dose-dependently. Fetus and fetal brain weights were significantly lower in all nicotine-treated groups. Light microscopy of hippocampal CA1 area showed a decrease in the number of cells per unit area. Electron microscopy of the same region revealed a dose-dependent increase in intracytoplasmic edema, mitochondrial swelling, dilation of rough endoplasmic reticulum, nuclear configurative abnormalities, and condensation of the nuclear chromatin. Nitrate + nitrite levels in fetal brain homogenates were significantly lower in the groups treated with 2 and 3 mg/kg NHT. Norepinephrine and normetanephrine (NMN) levels were significantly higher in 2 and 3 mg/kg NHT groups, as well as dopamine, 3-methoxy-4-hydroxyphenylethyleneglycole (MHPG), and dihydroxyphenylacetic acid levels in the 3-mg/kg NHT group. In conclusion, maternal nicotine exposure may lead to structural abnormalities of the fetal brain tissue and may result in decreased levels of NO and increased levels of catecholamines and their metabolites.
Department of Pharmacology, School of Medicine, Ege University, Bornova, Izmir 35100, Turkey. aytul@med.ege.edu.tr
Aytül
A
Onal
Ayşegül
A
Uysal
Sibel
S
Ulker
Yasemin
Y
Delen
Mine E
ME
Yurtseven
Akgün
A
Evinç
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D002395:Catecholamines / Q000502:physiology*; D003367:Cotinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000196:embryology / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity; D009569:Nitric Oxide / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000187:drug effects; D011247:Pregnancy; D017966:Pyramidal Cells / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats
D002395:Catecholamines; D018722:Nicotinic Agonists; D009569:Nitric Oxide; D009538:Nicotine; D003367:Cotinine