Alcoholic lung injury: Metabolic, biochemical and immunological aspects

Lata Kaphalia, William Calhoun

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Chronic alcohol abuse is a systemic disorder and a risk factor for acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). A significant amount of ingested alcohol reaches airway passages in the lungs and can be metabolized via oxidative and non-oxidative pathways. About 90% of the ingested alcohol is metabolized via hepatic alcohol dehydrogenase (ADH)-catalyzed oxidative pathway. Alcohol can also be metabolized by cytochrome P450 2E1 (CYP2E1), particularly during chronic alcohol abuse. Both the oxidative pathways, however, are associated with oxidative stress due to the formation of acetaldehyde and/or reactive oxygen species (ROS). Alcohol ingestion is also known to cause endoplasmic reticulum (ER) stress, which can be mediated by oxidative and/or non-oxidative metabolites of ethanol. An acute as well as chronic alcohol ingestions impair protective antioxidants, oxidize reduced glutathione (GSH, cellular antioxidant against ROS and oxidative stress), and suppress innate and adaptive immunity in the lungs. Oxidative stress and suppressed immunity in the lungs of chronic alcohol abusers collectively are considered to be major risk factors for infection and development of pneumonia, and such diseases as ARDS and COPD. Prior human and experimental studies attempted to identify common mechanisms by which alcohol abuse directly causes toxicity to alveolar epithelium and respiratory tract, particularly lungs. In this review, the metabolic basis of lung injury, oxidative and ER stress and immunosuppression in experimental models and alcoholic patients, as well as potential immunomodulatory therapeutic strategies for improving host defenses against alcohol-induced pulmonary infections are discussed.

Original languageEnglish (US)
Pages (from-to)171-179
Number of pages9
JournalToxicology Letters
Volume222
Issue number2
DOIs
StatePublished - Oct 4 2013

Fingerprint

Lung Injury
Alcohols
Lung
Alcoholism
Oxidative stress
Oxidative Stress
Endoplasmic Reticulum Stress
Adult Respiratory Distress Syndrome
Chronic Obstructive Pulmonary Disease
Pulmonary diseases
Reactive Oxygen Species
Eating
Antioxidants
Cytochrome P-450 CYP2E1
Acetaldehyde
Alcohol Dehydrogenase
Adaptive Immunity
Alcoholics
Infection
Innate Immunity

Keywords

  • ER stress
  • Ethanol
  • Lung
  • Metabolism
  • Oxidative stress

ASJC Scopus subject areas

  • Toxicology

Cite this

Alcoholic lung injury : Metabolic, biochemical and immunological aspects. / Kaphalia, Lata; Calhoun, William.

In: Toxicology Letters, Vol. 222, No. 2, 04.10.2013, p. 171-179.

Research output: Contribution to journalArticle

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