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)