The other nonoxidative pathway results in the formation of a type of fat molecule (i.e., lipid) containing phosphorus (i.e, phospholipid) known as phosphatidyl ethanol (see Figure 2). FAEEs are detectable in serum and other tissues after alcohol ingestion and persist long after alcohol is eliminated. The role of FAEEs in alcohol-induced tissue damage remains to be further evaluated.

Health Categories to Explore

Adolescent females with recent BD had ∼8% thicker cortices in the left frontal region than female non-drinkers, while adolescent males with BD had ∼7% thinner cortices, thus suggesting the presence of gender specific GM effects (Squeglia et al., 2012). Recent advances in neurotechnologies have opened new avenues of investigation into how alcohol-induced alterations in neural circuit activity influence ongoing behaviors and decision-making (Figure 2) [4,68]. Here we will review these advances, focusing on circuit- and receptor-level studies (for review of brain-wide neuronal networks see [69]). Recently, a genome-wide transcriptional assessment of human striatum found that G protein coupled receptors, the primary targets of many neurotransmitters and neuromodulators, were the top canonical pathway affected in striatum of AUD patients [70].

How Alcohol Affects Your Kidney Health

• Mitochondrial oxidative stress renders hepatocytes susceptible to ethanol- or acetaldehyde-induced mitochondrial membrane permeability transition (MMPT), apoptosis in chronic alcoholism and biliary cirrhosis [118].
• Transcription factors often form large multimeric protein complexes that bind to target gene promoters or enhancers to regulate the expression of mRNA.
• A better understanding of how alcohol affects these diverse and interlinked mechanisms may lead to the identification of novel therapeutic targets and to the development of much-needed novel, efficacious treatment options.
• Furthermore, dysregulation of striatal function can produce pathological drinking behaviors.

Alcohol also is metabolized in nonliver (i.e., extrahepatic) tissues that do not contain ADH, such as the brain, by the enzymes cytochrome P450 and catalase (see below). In general, alcohol metabolism is achieved by both oxidative pathways, which either add oxygen or remove hydrogen (through pathways involving ADH, cytochrome P450, and catalase enzymes), and nonoxidative pathways. Alcoholic beverages contain more than 200 compounds with different antioxidant activities to polyphenols, how does alcohol affect the kidneys including quercetin, catechin, tannic acids [80], and resveratrol, among others [81]. Resveratrol is a polyphenolic phytoalexin (trans-3,4′,5-trihydroxystilbene) present in purple grape juice, peanuts, and red wine [35,82] and has ability to prevent or slow the progression of a variety of pathologies [83]. It also possesses many health benefits that include cardioprotection [84]. The effects of alcohol on various tissues depend on its concentration in the blood over time.

Physical effects

Further, disrupted GABAergic transmission in this region is also linked to alcohol-induced cognitive impairments [107]. Together, altered excitability of striatal neurons and upstream cortical regulation of striatal activity influence a diverse range of drinking behaviors, which likely can be attributed to distinct striatal output circuits [108]. ROS, including superoxide (O2•−), hydrogen peroxide (H2O2), hypochlorite ion (OCl−), and hydroxyl (•OH) radicals, are naturally generated by many reactions in multiple regions of the cell. ROS act by “stealing” hydrogen atoms from other molecules, thereby converting those molecules into highly reactive free radicals. Alternatively, ROS can combine with stable molecules to form free radicals.

Variations in the rate of alcohol absorption, distribution, and elimination contribute significantly to clinical conditions observed after chronic alcohol con sumption. These variations have been attributed to both genetic and environmental factors, gender, drinking pattern, fasting or fed states, and chronic alcohol consumption. The second nonoxidative pathway requires the enzyme phospholipase D (PLD) (Laposata 1999), which breaks down phospholipids (primarily phosphatidylcholine) to generate phosphatidic acid (PA). PLD has a high Km for ethanol, and the enzymatic reaction does occur predominantly at high circulating alcohol concentrations. The product of this reaction, phosphatidyl ethanol, is poorly metabolized and may accumulate to detectable levels following chronic consumption of large amounts of alcohol, but its effects on the cell remain to be established. However, the formation of phosphatidyl ethanol occurs at the expense of the normal function of PLD, namely to produce PA, resulting in inhibited PA formation and disruption of cell signaling.

Chronic excessive alcohol consumption and heart damages

Unfortunately, the incidence of heart disease due to chronic alcohol consumption continues to rise owing to the increased chronic alcohol drinking habits among American youth. In fact, individuals who abuse alcohol have been shown to have a high percentage of cardiovascular disease; the leading cause of death, disability, and healthcare expense in the United States. The DA system has been linked with reinforcing properties of alcohol abuse and the administration of DA receptor antagonists in the nucleus accumbens attenuates alcohol self-administration in rats (Wise and Rompre, 1989; Rassnick et al., 1992). Repeated alcohol use resulted in reduced DA production and receptors in human alcoholics with D2 receptors further reinforcing the effects of alcohol (Stefanini et al., 1992; Volkow et al., 1996; Nowak et al., 2000). In parallel, P rats have fewer D2 receptors in the limbic system relative to wildtype rats (Stefanini et al., 1992; McBride et al., 1993). Thanos et al. (2001) found that adenovirus vector mediated overexpression of D2 receptors reduced alcohol self-administration by 64% and preference by 43% in P rats.

For example, the activity of mRNA binding protein fragile-X mental retardation protein (Fmrp), which plays an important role in translation [47], is enhanced by alcohol in the hippocampus of mice resulting in alteration in the expression of synaptic proteins [48]. Additionally, Fmrp in the hippocampus plays a role in the acute antidepressant actions of alcohol [49]. Interestingly, rapid antidepressants require coordinated actions of Fmrp and mTORC1 [50], raising the possibility that such coordination may also be relevant in the context of alcohol’s actions. Alcohol use produces wide-ranging, diverse effects on the central nervous system. It influences intracellular signaling mechanisms, leading to changes in gene expression, chromatin remodeling and translation. As a result of these molecular alterations, alcohol affects the activity of neuronal circuits.

Long-term effects

Proinflammatory cytokines and chemokines are markedly increased in the livers of patients with alcoholic hepatitis, a disease caused by chronic alcohol consumption (McClain et al., 1999). Since alcohol induced damage is mediated by enzymes that carry out alcohol metabolism, having similar enzymes is critical in studying alcoholic liver damage. The physiology of the pig liver is more comparable to the human liver because it produces similar enzymes (e.g., CYP2E1 and its isoforms) with greater homology (Figure 1). All the main metabolic activities in human CYP enzymes are present in the porcine liver microsomes including CYP1A, 2A, 2C, 2D, 2E1, and 3A (Anzenbacher et al., 1998; Monshouwer et al., 1998). Rats possess variation in the composition of principal CYP isoforms relative to humans and uninduced rats (wildtypes rats that are not pretreated with agonists to elicit enzyme activity) lack a direct counterpart to some human CYP enzymes. For example, CYP2B is the most prominent isoform in rats responsible for biotransformation of many drugs, while CYP2B is absent in both human and pig liver microsomes.

From the first sip, alcohol impacts the body—even if you don’t realize it. Any amount of alcohol can diminish your judgment and functioning, and even low or moderate alcohol use can have harmful effects on different organs. A standard drink size looks different depending on the type of alcohol you choose. According to the CDC, a standard U.S. drink includes 0.6 ounces of pure alcohol; the same amount of pure alcohol is generally found in 12 ounces of beer, 5 ounces of wine and 1.5 ounces of 80-proof distilled spirits or liquor. “It used to be thought that it’s only heavy alcohol use, but now the understanding is that any alcohol during pregnancy can expose the unborn fetus to fetal alcohol syndrome,” he says. If a drink or two leaves you ready for bed, you might be surprised to learn that drinking alcohol is linked to insomnia, or trouble falling — and staying — asleep.

Consequences of Alcohol Metabolism

What is the role of changes in redox state on the expression of cytokines that promote or prevent inflammatory reactions? What are the interactions between ethanol metabolism, diabetes, and obesity? Answers to these and other questions will further elucidate the mechanisms underlying ethanol’s metabolism and their regulation, as well as the effects that alcohol metabolism and its byproducts have on all tissues and organs throughout the body. In addition, a deeper understanding of these processes will allow researchers to design intervention strategies that may ameliorate the harmful effects of alcohol and its metabolites. Brain mitochondria appear to be the principal targets of the oxidative stress generated by ethanol intoxication and withdrawal. This stress causes extensive degradation and depletion of brain mtDNA in mice [135] and decreases cytochrome c oxidase (COX) activity in a variety of neurodegenerative illnesses, such Parkinson disease and Alzheimer disease (AD).