Hybrid Malondialdehyde and Acetaldehyde Protein Adducts Form in the Lungs of Mice Exposed to Alcohol and Cigarette Smoke

Abstract

Background Most alcohol abusers smoke cigarettes and approximately half of all cigarette smokers consume alcohol. However, no animal models of cigarette and alcohol co-exposure exist to examine reactive aldehydes in the lungs. Cigarette smoking results in elevated lung acetaldehyde (AA) and malondialdehyde (MDA) levels. Likewise, alcohol metabolism produces AA via the action of alcohol dehydrogenase and MDA via lipid peroxidation. A high concentration of AA and MDA form stable hybrid protein adducts known as malondialdehyde-acetaldehyde (MAA) adducts. We hypothesized that chronic cigarette smoke and alcohol exposure in an in vivo mouse model would result in the in vivo formation of MAA adducts. Methods We fed C57BL/6 mice ad libitum ethanol (20%) in drinking water and exposed them to whole body cigarette smoke 2 hour/d, 5d/week for 6 weeks. Bronchoalveolar lavage fluid and lung homogenates were assayed for AA, MDA, and MAA adduct concentrations. MAA-adducted proteins were identified by Western blot and ELISA. Results Smoke and alcohol exposure alone elevated both AA and MDA, but only the combination of smoke+alcohol generated protein-adducting concentrations of AA and MDA. MAA-adducted protein (~500ng/ml) was significantly elevated in the smoke+alcohol-exposed mice. Of the five MAA-adducted proteins identified by Western blot, one protein band immunoprecipitated with antibodies to surfactant protein D. Similar to in vitro PKC stimulation by purified MAA-adducted protein, PKC epsilon was activated only in tracheal epithelial extracts from smoke and alcohol-exposed mice. Conclusions These data demonstrate that only the combination of cigarette smoke exposure and alcohol feeding in mice results in the generation of significant AA and MDA concentrations, the formation of MAA-adducted protein, and the activation of airway epithelial PKC epsilon in the lung.

Malondialdehyde epitopes as mediators of sterile inflammation

“…In the first model for examining effects of in vivo MDA generation, mice were exposed to tobacco smoke and alcohol, which induce oxidative stress in the lung and consequently high levels of two aldehydes in the bronchoalveolar lavage fluid, acetaldehyde and malondialdehyde [70]. These can react together to form hybrid adducts termed malondialdehyde-acetaldehyde (MAA) adducts with pulmonary proteins such as SPD.…”

“…Protein D (SPD, discussed below) [70]. However, we still lack a better understanding of the conditions under which these modifications occur in vivo and to what consequences they might lead.…”

Aldehyde-modified proteins as mediators of early inflammation in atherosclerotic disease

“…These findings have translated to human studies as well, in which IgG anti-MAA levels are correlated to the severity of liver injury and cirrhosis [73,75]. Researchers have also demonstrated MAA adducts in airway epithelial cells exposed in vivo to ethanol and tobacco smoke and demonstrated associated release of proinflammatory cytokines via scavenger-receptor-mediated binding of these adducts [54,[76][77][78]. Furthermore, exposure of airway epithelial cells to MAA-adducted proteins has been shown to cause lung inflammation [79], which also results in a decrease in the migration of epithelial cells into injured lung tissue and affects tissue repair and remodeling [80].…”

Vitamin C-E ve Monosodyum Glutamata Bağlı Ovaryan Toksisite

“…The ovariumMDA is a decomposition product of peroxidized polyunsaturated fatty acids that as marker for detection of ROS reactivity toward lipid peroxidation 20,21 .This altered lipid profile accompanied with elevation in reactive oxygen species formation and reduction of antioxidant activities, including SOD and GSH-Px 9,22 .…”