4-Methylpyrazole, an alcohol dehydrogenase inhibitor, exacerbates alcohol-induced microencephaly during the brain growth spurt

Alcohol
W J ChenJ R West

Abstract

Whether alcohol-induced microencephaly occurs as a result of the effect of alcohol or acetaldehyde remains an unanswered, yet important, question. The present study addressed this issue by using an alcohol dehydrogenase (ADH) inhibitor, 4-methylpyrazole (4-MP), that works by blocking the metabolism of alcohol to its primary metabolite acetaldehyde, thereby prolonging the actions of alcohol while minimizing the generation of acetaldehyde. Four groups of artificially reared Sprague-Dawley rat pups were treated with alcohol treatment (3.3 g/kg EtOH or isocalorically matched control formula from postnatal days 4 through 9) and 4-MP administration (IP, 50 mg/kg or saline). A suckle control group was introduced to control the effects of the artificial rearing procedure. On postnatal day 10, all pups were perfused. Alcohol in combination with 4-MP treatment produced a marked microencephaly, as assessed by brain weights or brain to body weight ratios, compared with other artificially reared groups. The peak BACs in the pups that received both alcohol and 4-MP were increased at least twofold compared with those that received alcohol alone. These findings indicate that 4-MP is an effective nontoxic ADH inhibitor and that microencephaly i...Continue Reading

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Citations

Jan 9, 2013·Applied Biochemistry and Biotechnology·Jinjing WangQi Li
May 15, 2002·The International Journal of Biochemistry & Cell Biology·Patrick SauvantVéronique Azaïs-Braesco
Aug 16, 2001·Alcoholism, Clinical and Experimental Research·W J ChenJ R West
Feb 26, 2016·Neuroscience and Biobehavioral Reviews·Christine J FontaineBrian R Christie
Sep 29, 2004·Neurotoxicology and Teratology·Mark J ReimersRobert L Tanguay

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