Effects of ethanol and diphenyl diselenide exposure on the activity of delta-aminolevulinate dehydratase from mouse liver and brain.
Ethanol toxicity is affected by both environmental and inherited features. Since oxidative stress is an important molecular mechanism for ethanol-induced cellular damage, the concomitant exposure to ethanol and pro-oxidative or antioxidant compounds can alter its toxicity. Here, we investigate the effects of exposure to ethanol and/or diphenyl diselenide, an organochalcogen with antioxidant properties, on parameters related to oxidative stress (thiobarbituric acid reactive species-TBARS-and delta-aminolevulinate dehydratase-delta-ALA-D activity) in mouse liver and brain. In addition, the in vitro effects of ethanol and acetaldehyde on the activity of delta-ALA-D from human erythrocytes were also investigated. Both ethanol and diphenyl diselenide decreased hepatic delta-ALA-D activity and DL-dithiothreitol (DTT) reactivated this enzyme only after ethanol-induced inhibition. Moreover, ethanol increased liver TBARS levels, independently of the presence of diphenyl diselenide treatment. Brain delta-ALA-D activity and TBARS levels were not changed by ethanol or diphenyl diselenide exposure. Under in vitro conditions, acetaldehyde was a more potent inhibitor of delta-ALA-D from human erythrocytes when compared to ethanol, demonstrating a dose-dependent effect. This study indicates that (1) hepatic delta-ALA-D is a molecular target for the damaging effect of ethanol under in vivo conditions; (2) diphenyl diselenide and ethanol seem to inhibit delta-ALA-D by different mechanisms; (3) acetaldehyde, a metabolite of ethanol, is probably the main molecule responsible for the inhibitory effects of the parent compound on delta-ALA-D.
Fachinetto
Roselei
R
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Pivetta
Lucinéia A
LA
Farina
Marcelo
M
Pereira
Romaiana P
RP
Nogueira
Cristina W
CW
Rocha
João B T
JB
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000623:Porphobilinogen Synthase / Q000096:biosynthesis*
D000975:Antioxidants; D001555:Benzene Derivatives; D016566:Organoselenium Compounds; C061132:diphenyldiselenide; D000431:Ethanol; D000623:Porphobilinogen Synthase