Chronic Ethanol Consumption and Thiamine Deficiency Modulate β-Amyloid Peptide Level and Oxidative Stress in the Brain

Alcohol and Alcoholism, Mar 2017

The effects of chronic ethanol (EtOH) consumption, associated or not with thiamine deficiency (TD), on β-amyloid peptide (Aβ) level and oxidative stress in the brain were studied in male C57BL/6 mice.

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Chronic Ethanol Consumption and Thiamine Deficiency Modulate β-Amyloid Peptide Level and Oxidative Stress in the Brain

Alcohol and Alcoholism Chronic Ethanol Consumption and Thiamine Deficiency Modulate β-Amyloid Peptide Level and Oxidative Stress in the Brain Yu-Shi Gong 0 Juan Guo 0 Kun Hu 0 Yong-Qing Gao 0 Fang-Li Hou 0 Feng-Lin Song 0 Cui-Yi Liang 0 0 School of Food Science, Guangdong Pharmaceutical University , Zhongshan 528458 , China Aims: The effects of chronic ethanol (EtOH) consumption, associated or not with thiamine deficiency (TD), on β-amyloid peptide (Aβ) level and oxidative stress in the brain were studied in male C57BL/6 mice. Methods: Mice were prepared by feeding with an EtOH liquid diet, thiamine-depleted liquid diet and a thiamine-depleted EtOH liquid diet for 7 weeks. Biochemical parameters were measured by corresponding commercial kits. Results: EtOH consumption or TD induced a significant decrease in the thiamine level, but induced increased in the β-amyloid peptide 1-42 and β-amyloid peptide 1-40 (Aβ1-40) levels. EtOH consumption led to a significant increase in the malondialdehyde (MDA) and nitric oxide (NO) levels, total nitric oxide synthase (NOS) activities and inducible nitric oxide synthase (iNOS) activities, but a significant decrease in superoxide dismutase (SOD) and glutathione peroxidase activities. TD significantly elevated the MDA content and total NOS and iNOS activities but lowered SOD activity. Aβ1-40 overproduction, the change in the NO level, and SOD activity in the brain induced by chronic EtOH treatment associated with TD were greater than that induced by EtOH or TD alone. Conclusion: Findings from this report suggested that chronic EtOH consumption could induce TD, excess Aβ production and oxidative damage, and the association with TD should have more severe effects on the brain. Short summary: Chronic EtOH consumption or thiamine deficiency (TD) treatment could reduce the thiamine level, induce β-amyloid peptide (Aβ) overproduction and oxidative stress in the brain. When associated with TD, EtOH consumption caused Aβ overproduction and oxidative damage more serious. INTRODUCTION Ethanol (EtOH) has complex effects on the brain. Light-to-moderate alcohol consumption is associated with a decrease in degeneration of the nervous system, and lower risk of dementia and Alzheimer’s disease (AD) (Berntsen et al., 2015; Muñoz et al., 2015) . Conversely, several studies suggested a neurotoxic effect of high amounts of alcohol intake and an increased risk of developing a dementia-like condition, such as AD (Ruitenberg et al., 2002; Tiwari and Chopra, 2013) . Chronic EtOH consumption induces free radical production, which led to oxidative damage (Skrzydlewska et al., 2005; Tiwari and Chopra, 2013) . Thiamine deficiency (TD), which is found in a large number of alcoholics, is an important contributor to alcoholrelated brain damage (Martin et al., 2003; Day et al., 2013; Latt and Dore, 2014) . TD induces chronic mild impairment of oxidative metabolism and promotes selective changes in oxidative stress and inflammation that led to neuronal loss in specific brain regions (Ke et al., 2003; Ke and Gibson, 2004) . Several studies have reported that TD enhances β-amyloid peptide (Aβ) accumulation, thereby exacerbating TD-induced oxidative stress in an Alzheimer’s mouse model (Karuppagounder et al., 2009; Zhang et al., 2011) . Given that chronic alcohol abuse causes malnourishment such as TD, which can enhance Aβ accumulation and oxidative damage in the brain, whether chronic alcoholism may cause excess Aβ production is unclear. Therefore, we decided to study the effect of chronic alcohol intake on Aβ release and some representative biological markers related to oxidative stress. Although the occurrence of dementia and neurodegeneration induced by alcohol and TD alone is well supported by multiple studies, the mechanisms of their neurotoxicity remain unclear. Moreover, in recent years, information regarding the comparative effects of EtOH and TD on brain damage has been limited ( Pires et al., 2001 ; Martin et al., 2003; Mulholland et al., 2005; Bâ, 2011 ; De Fátima Oliveira-Silva et al., 2015; Vedder et al., 2015). The role of oxidative stress and neurotransmitter alterations in TD associated with alcohol brain disease has been revealed (De Fátima Oliveira-Silva et al., 2015; Vedder et al., 2015) . Few reports have been conducted on the effect of alcohol intake or TD treatment on Aβ action, which plays a critical pathogenic role in the onset and development of AD. For further understanding of their synergistic interactions and the role of TD in alcohol-induced brain damage, we aimed to assess the contribution of chronic EtOH consumption, associated or not with TD in the Aβ levels and oxidative damage in the brain. MATERIALS AND METHODS Animal procedures The experimental protocols were approved by Animal Care and Use Committee of the Guangdong Pharmaceutical University, with the reference number of gdpu2016001. Five-week-old C57BL/6 male mice were obtained from the Center fo (...truncated)


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Gong, Yu-Shi, Guo, Juan, Hu, Kun, Gao, Yong-Qing, Hou, Fang-Li, Song, Feng-Lin, Liang, Cui-Yi. Chronic Ethanol Consumption and Thiamine Deficiency Modulate β-Amyloid Peptide Level and Oxidative Stress in the Brain, Alcohol and Alcoholism, 2017, pp. 159-164, Volume 52, Issue 2, DOI: 10.1093/alcalc/agw095