Alcohol in moderation, cardioprotection, and neuroprotection: epidemiological considerations and mechanistic studies - PubMed (original) (raw)

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Alcohol in moderation, cardioprotection, and neuroprotection: epidemiological considerations and mechanistic studies

Michael A Collins et al. Alcohol Clin Exp Res. 2009 Feb.

Abstract

In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating the beneficial effects of light-moderate, nonbinge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti-inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. Also, brain functional comparisons between older moderate alcohol consumers and nondrinkers have received more recent epidemiological study. In over half of nearly 45 reports since the early 1990s, significantly reduced risks of cognitive loss or dementia in moderate, nonbinge consumers of alcohol (wine, beer, liquor) have been observed, whereas increased risk has been seen only in a few studies. Physiological explanations for the apparent CNS benefits of moderate consumption have invoked alcohol's cardiovascular and/or hematological effects, but there is also experimental evidence that moderate alcohol levels can exert direct "neuroprotective" actions-pertinent are several studies in vivo and rat brain organotypic cultures, in which antecedent or preconditioning exposure to moderate alcohol neuroprotects against ischemia, endotoxin, beta-amyloid, a toxic protein intimately associated with Alzheimer's, or gp120, the neuroinflammatory HIV-1 envelope protein. The alcohol-dependent neuroprotected state appears linked to activation of signal transduction processes potentially involving reactive oxygen species, several key protein kinases, and increased heat shock proteins. Thus to a certain extent, moderate alcohol exposure appears to trigger analogous mild stress-associated, anti-inflammatory mechanisms in the heart, vasculature, and brain that tend to promote cellular survival pathways.

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Figures

Figure 1

Figure 1. The relationships of alcohol intake with risks of coronary heart disease, ischemic stroke, and dementia among participants in the Cardiovascular Health Study

Long-term abstainers were the reference category. The Y-axis indicates hazard ratios for coronary heart disease and ischemic stroke, and odds ratios for dementia. See text for appropriate references.

Figure 2

Figure 2. Moderate drinking and mitochondrial protein kinase Cε localization

Adult male C57BL/6 mice were fed 10% alcohol (vol/vol) in drinking water for 12 weeks as described (Zhou et al., 2004). Mitochondrial fractions were prepared from isolated hearts by differential centrifugation. (A) Western blot analysis of mitochondrial fractions from normoxic hearts. Moderate alcohol intake had no significant effects on mitochondrial protein kinase Cε expression. (B) Alcohol consumption produced a 3-fold increase in mitochondrial protein kinase Cε in hearts following 25 min ischemia and 30 min reperfusion on a Langendorff apparatus.

Figure 3

Figure 3. Protein kinase Cε is a key factor in alcohol-mediated cardioprotection

Submitochondrial particles were prepared as described (Zhou et al., 2004) from hearts of alcohol-fed (black bars) and control (white bars) mice and used to measure respiratory chain complex activities after ischemia-reperfusion. (A) Moderate alcohol intake significantly improved mitochondrial NADH-oxidase activity after stress. In contrast, sustained cardioprotection was blocked by a protein kinase Cε antagonist peptide and in knockout mice. (B) Chronic protection against NADH-Q1 reductase (Complex I) injury was also abolished by protein kinase C inhibition. n = 6 hearts per condition. *P<0.05 vs. control ischemia-reperfusion hearts.

Figure 4

Figure 4

**A. Cardioprotective and molecular targets of alcohol.**Cardioprotective targets are shown on the right whereas the molecular targets are shown on the left. B. Cardioprotective and molecular targets of resveratrol. Cardioprotective targets are shown on the right whereas the molecular targets are shown on the left.

Figure 4

Figure 4

**A. Cardioprotective and molecular targets of alcohol.**Cardioprotective targets are shown on the right whereas the molecular targets are shown on the left. B. Cardioprotective and molecular targets of resveratrol. Cardioprotective targets are shown on the right whereas the molecular targets are shown on the left.

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