Neurotoxicity and induction of fibroblast proliferation by acetaldehyde in the rabbit liver.
1. Acetaldehyde may, directly or through the formation of condensation products with biogenic amines, be involved in the pathogeny of alcoholic disease. 2. Rabbits were treated acutely (200 mg kg-1, i.p., 1 h before sacrifice) or subacutely (200 mg kg-1 per day, during 5 days; sacrificed 2 days after end of treatment) with acetaldehyde. Another group was administered 6-OHDA (2 x 50 mg kg-1 on day 0 and on day 1, killed on day 5). 3. Acetaldehyde induced a depletion of hepatic noradrenaline. Both in the acute experiments and 2 days after the subacute treatment with acetaldehyde the levels of hepatic noradrenaline were 25% of control. These effects were similar to, but less intense than those induced by 6-OHDA. 4. Both subacute acetaldehyde and 6-OHDA led to a significant increase in the density of fibroblasts in the portal tract spaces of the rabbit liver. 5. The neurotoxic effects of acetaldehyde and the subsequent increase in liver fibroblast density may play a role in the pathogenesis of alcoholic disease.
Matias
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A
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Soares-da-Silva
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P
Azevedo
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I
D000079:Acetaldehyde / Q000633:toxicity*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000294:innervation*; D009422:Nervous System Diseases / Q000139:chemically induced*; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects*
D016627:Oxidopamine; D000079:Acetaldehyde; D009638:Norepinephrine