Alcohol Research : Current Reviews最新文献

Adolescence typically is a time of experimentation, including alcohol use and, particularly, binge drinking. Because the brain is still developing during adolescence, such exposure could have long-lasting effects. Animal models and adolescent intermittent ethanol exposure (AIE) paradigms have been used to help elucidate the consequences of adolescent binge drinking. These studies have identified cognitive deficits, particularly in challenging cognitive tasks, and behavioral alterations such as greater risk preferences, impulsivity, and disinhibition. AIE also is associated with changes in affect when the animals reach adulthood, including increased social anxiety and, sometimes, general anxiety. Animal models have demonstrated that AIE can result in retention of certain alcohol-related adolescent phenotypes (i.e., reduced sensitivity to alcohol's aversive effects and increased sensitivity to alcohol's rewarding effects) into adulthood, which may motivate continued elevated alcohol use. The detrimental effects of adolescent alcohol exposure extend to a diversity of lasting alterations in the brain, including reduced neurogenesis, increased proinflammatory responses, changes in gene expression through epigenetic mechanisms, and alterations in the activities of various neurotransmitter systems. Further exploration of these mechanisms in animal models and humans may lead to improved prevention and intervention efforts.

Findings from epidemiologic studies and research with experimental animal models provide insights into alcohol-related disease pathogeneses. Epidemiologic data indicate that heavy drinking and smoking are associated with high rates of pancreatic disease. Less clear is the association between lower levels of drinking and pancreatitis. Intriguingly, a very low percentage of drinkers develop clinical pancreatitis. Experimental models demonstrate that alcohol administration alone does not initiate pancreatitis but does sensitize the pancreas to disease. Understanding the effects of alcohol use on the pancreas may prove beneficial in the prevention of both pancreatitis and pancreatic cancer.

Among the many organ systems affected by harmful alcohol use, the lungs are particularly susceptible to infections and injury. The mechanisms responsible for rendering people with alcohol use disorder (AUD) vulnerable to lung damage include alterations in host defenses of the upper and lower airways, disruption of alveolar epithelial barrier integrity, and alveolar macrophage immune dysfunction. Collectively, these derangements encompass what has been termed the "alcoholic lung" phenotype. Alcohol-related reductions in antioxidant levels also may contribute to lung disease in people with underlying AUD. In addition, researchers have identified several regulatory molecules that may play crucial roles in the alcohol-induced disease processes. Although there currently are no approved therapies to combat the detrimental effects of chronic alcohol consumption on the respiratory system, these molecules may be potential therapeutic targets to guide future investigation.

Skeletal muscle dysfunction (i.e., myopathy) is common in patients with alcohol use disorder. However, few clinical studies have elucidated the significance, mechanisms, and therapeutic options of alcohol-related myopathy. Preclinical studies indicate that alcohol adversely affects both anabolic and catabolic pathways of muscle-mass maintenance and that an increased proinflammatory and oxidative milieu in the skeletal muscle is the primary contributing factor leading to alcohol-related skeletal muscle dysfunction. Decreased regenerative capacity of muscle progenitor cells is emerging as an additional mechanism that contributes to alcohol-induced loss in muscle mass and impairment in muscle growth. This review details the epidemiology of alcoholic myopathy, potential contributing pathophysiologic mechanisms, and emerging literature on novel therapeutic options.

Adolescence represents a vulnerable period for developing youth. Alcohol use and misuse are especially problematic behaviors during this time. Adolescents are more sensitive to alcohol and less tolerant of its detrimental effects than are adults. Research in humans and animals has revealed that early alcohol consumption can result in delayed pubertal development. Animal studies have shown that alcohol detrimentally affects neuroendocrine systems within the hypothalamic region of the brain that are associated with the normal, timely onset of the pubertal process. To effectively restore development and shorten recovery time associated with the adverse effects of alcohol on puberty, researchers must first understand the molecular and physiological mechanisms by which alcohol interferes with critical hypothalamic functions.

Alcohol use has complex effects on cardiovascular (CV) health. The associations between drinking and CV diseases such as hypertension, coronary heart disease, stroke, peripheral arterial disease, and cardiomyopathy have been studied extensively and are outlined in this review. Although many behavioral, genetic, and biologic variants influence the interconnection between alcohol use and CV disease, dose and pattern of alcohol consumption seem to modulate this most. Low-to-moderate alcohol use may mitigate certain mechanisms such as risk and hemostatic factors affecting atherosclerosis and inflammation, pathophysiologic processes integral to most CV disease. But any positive aspects of drinking must be weighed against serious physiological effects, including mitochondrial dysfunction and changes in circulation, inflammatory response, oxidative stress, and programmed cell death, as well as anatomical damage to the CV system, especially the heart itself. Both the negative and positive effects of alcohol use on particular CV conditions are presented here. The review concludes by suggesting several promising avenues for future research related to alcohol use and CV disease. These include using direct biomarkers of alcohol to confirm self-report of alcohol consumption levels; studying potential mediation of various genetic, socioeconomic, and racial and ethnic factors that may affect alcohol use and CV disease; reviewing alcohol-medication interactions in cardiac patients; and examining CV effects of alcohol use in young adults and in older adults.

Chronic alcohol consumption is a well-known risk factor for tissue injury. The link between alcohol use disorder (AUD) and kidney injury is intriguing but controversial, and the molecular mechanisms by which alcohol may damage the kidneys are poorly understood. Epidemiological studies attempting to link AUD and kidney disease are, to date, inconclusive, and there is little experimental evidence directly linking alcohol consumption to kidney injury. However, studies conducted primarily in other organs and tissues suggest several possible mechanisms by which alcohol may promote kidney dysfunction. One possible mechanism is oxidative stress resulting from increased production of reactive oxygen species, which leads to an excessive amount of free radicals, which in turn trigger tissue injury and increase inflammation. In addition, AUD's effect on other major organs (liver, heart, intestines, and skeletal muscle) appears to promote unfavorable pathological processes that are harmful to the kidneys. Notably, these mechanisms have not yet been validated experimentally in the kidney. Additional research is needed to clarify if alcohol does indeed promote kidney injury and the mechanisms by which alcohol-induced kidney injury may occur.

In large amounts, alcohol and its metabolites can overwhelm the gastrointestinal tract (GI) and liver and lead to damage both within the GI and in other organs. Specifically, alcohol and its metabolites promote intestinal inflammation through multiple pathways. That inflammatory response, in turn, exacerbates alcohol-induced organ damage, creating a vicious cycle and leading to additional deleterious effects of alcohol both locally and systemically. This review summarizes the mechanisms by which chronic alcohol intake leads to intestinal inflammation, including altering intestinal microbiota composition and function, increasing the permeability of the intestinal lining, and affecting the intestinal immune homeostasis. Understanding the mechanisms of alcohol-induced intestinal inflammation can aid in the discovery of therapeutic approaches to mitigate alcohol-induced organ dysfunctions.

Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse results in clinical abnormalities of one of the body's most important systems, the endocrine system. This system ensures proper communication between various organs, also interfacing with the immune and nervous systems, and is essential for maintaining a constant internal environment. The endocrine system includes the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-growth hormone/insulin-like growth factor-1 axis, and the hypothalamic-posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol's effects on various components of the endocrine system and their consequences.