Chronic ethanol and iron administration on iron content, neuronal nitric oxide synthase, and superoxide dismutase in rat cerebellum.
Excessive chronic ethanol administration to animals has been shown to cause oxidative insults to many body organs, including the liver and brain. In many instances, iron supplementation to the diet may further aggravate ethanol-induced liver damage. However, whether increased dietary iron can enhance the damage in the brain is unknown. In this study, four groups of Sprague-Dawley rats were fed a Lieber-DeCarli liquid diet containing 5% (w/v) ethanol or isocaloric amount of maltase and/or 0.25% (w/v) carbonyl iron for 2 months. At the end of the feeding regimen, iron contents were determined in the plasma, liver, cerebral cortex, and cerebellum. Cerebellar superoxide dismutase (SOD) and nitric oxide synthase (NOS) activities were measured and mRNA levels of MnSOD, CuZnSOD, and nNOS in the cerebellar granule cell layer were quantitated by in situ hybridization. Ethanol treatment alone caused an increase in iron levels in plasma, no change in the liver and cerebral cortex, but a decrease in the cerebellum. Iron supplementation increased liver iron >4-fold but did not alter iron contents in the cerebellum and cortex. All of the mRNA species examined and SOD activity were not affected by either iron or ethanol administration. However, NOS activity in the cerebellum was significantly enhanced by ethanol, whereas iron supplementation had an opposite effect. Our results indicate that iron supplementation to animals consuming ethanol may have tissue-specific effects. Furthermore, ethanol-induced increase in NOS activity in the cerebellum may explain the sensitivity of cerebellar neurons to oxidative insult.
Xia
J
J
Department of Biochemistry and Pathology, University of Missouri, Columbia 65212, USA.
Simonyi
A
A
Sun
G Y
GY
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002531:Cerebellum / Q000737:chemistry* / Q000187:drug effects*; D004032:Diet / Q000009:adverse effects*; D000431:Ethanol / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D007501:Iron / Q000009:adverse effects / Q000032:analysis / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000032:analysis*
D000431:Ethanol; D007501:Iron; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase