Alcoholic lung injury: Metabolic, biochemical and immunological aspects

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.

Alcoholic lung injury: pineapple peel extract modulates antioxidant enzymes and attenuates lipid peroxidation in rat models

“…5 and 6) indicates an occurrence of oxidative stress. Lipid peroxidation has been shown to alter membrane integrity, disrupting normal signaling events required for homeostasis and cause cell injury [3]. The observed significant (p < 0.05) reversal on treatment with pineapple peel extract further portrays the antioxidant protective potential of the extract against alcohol -induced oxidative damage in lungs.…”

“…This is usually excreted in exhaled breath but local metabolism within the lungs has been shown to cause an altered redox status with increased ROS production leading to oxidative injury [2,3,18]. In this study, oxidative injury was induced in rat lungs by alcohol and treated with pineapple peel methanolic extract.…”

“…A substantial dose of alcohol ingested has been reported to reach the airway passages by the bronchial circulation directly through the ciliated epithelium and metabolized by oxidative and/or nonoxidative pathways [2,3]. This is usually excreted in exhaled breath but local metabolism within the lungs has been shown to cause an altered redox status with increased ROS production leading to oxidative injury [2,3,18].…”

“…GSH is a major endogenous antioxidant, which counteracts free-radical-mediated damage and a major determining factor in alcoholic lung disease [19]. Reduced GSH level has been reported in chronic alcohol ingestion within the alveolar space, leading to an impairment of alveolar immunity and thus increasing the lung susceptibility to oxidant-mediated injury [3]. The observed increased level in the extract -treated rats insinuates a therapeutic potential of the pineapple peel against alcoholic lung disease.…”

“…Oxidative stress has been described as a major facet of alcohol induced tissue injury and machinery in alcoholic lung disease as well as other diseases [1][2][3]. H 2 O 2 produced during alcohol metabolism to acetaldehyde by cytochrome P450-2E1 (CYP2E1) in both liver and lungs interacts with copper/iron leading to generation of Reactive Oxygen Species (ROS) and/or its products [4,5].…”