Catalase mediates acetaldehyde formation in the striatum of free-moving rats.
Using brain microdialysis, we measured both ethanol (EtOH) and acetaldehyde (AcH) levels in the striatum of free-moving rats following the inhibition of EtOH oxidation pathways. Rats received intraperitoneal EtOH (1g/kg) alone or in combination with 4-methylpyrazole (MP, 82 mg/kg, an alcohol dehydrogenase inhibitor), and/or catalase inhibitor sodium azide (AZ, 10mg/kg) or 3-amino-1,2,4-triazole (AT, 1g/kg), and/or cyanamide (CY, 50mg/kg, an aldehyde dehydrogenase inhibitor). Results revealed that both EtOH and AcH concentrations reached a plateau at 30 min after a dose of EtOH, and then gradually decreased for 4h. AcH was identified in the CY+EtOH, CY+AT/AZ+EtOH, and CY+4-MP+EtOH groups. The CY+EtOH-induced peak AcH level was 195.2+/-19.4 microM, and this level was significantly higher than the values in other groups studied. The catalase or ADH inhibitor in combination with CY lowered considerably the AcH concentration in the brain. The EtOH level reached a maximum of 25.9+/-2.3 mM in the CY+4-MP+EtOH group, and this level was markedly higher than in the EtOH group. No significant difference in brain EtOH levels was seen in any of the other groups examined. The findings strongly support the assumption that the enzyme catalase plays a significant role in AcH formation directly in the rat brain.
Jamal
Mostofa
M
Department of Forensic Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. jamaldr68@yahoo.com
Ameno
Kiyoshi
K
Uekita
Ikuo
I
Kumihashi
Mitsuru
M
Wang
Weihuan
W
Ijiri
Iwao
I
D000079:Acetaldehyde / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002849:Chromatography, Gas; D003484:Cyanamide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism*; D000077604:Fomepizole; D008124:Locomotion; D008297:Male; D017551:Microdialysis; D010084:Oxidation-Reduction; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019810:Sodium Azide / Q000494:pharmacology; D013997:Time Factors
D004791:Enzyme Inhibitors; D011720:Pyrazoles; D000431:Ethanol; D003484:Cyanamide; D000077604:Fomepizole; D019810:Sodium Azide; D000426:Alcohol Dehydrogenase; D002374:Catalase; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D000640:Amitrole