title: Dietary antioxidants prevent alcohol-induced ciliary dysfunction.
abstract: Previously we have shown that chronic alcohol intake causes alcohol-induced ciliary dysfunction (AICD), leading to non-responsive airway cilia. AICD likely occurs through the downregulation of nitric oxide (NO) and cyclic nucleotide-dependent kinases, protein kinase G (PKG) and protein kinase A (PKA). Studies by others have shown that dietary supplementation with the antioxidants N-acetylcysteine (NAC) and procysteine prevent other alcohol-induced lung complications. This led us to hypothesize that dietary supplementation with NAC or procysteine prevents AICD. To test this hypothesis, C57BL/6 mice drank an alcohol/water solution (20% w/v) ad libitum for 6 weeks and were concurrently fed dietary supplements of either NAC or procysteine. Ciliary beat frequency (CBF) was measured in mice tracheas, and PKG/PKA responsiveness to β-agonists and NOx levels were measured from bronchoalveolar lavage (BAL) fluid. Long-term alcohol drinking reduced CBF, PKG and PKA responsiveness to β-agonists, and lung NOx levels in BAL fluid. In contrast, alcohol-drinking mice fed NAC or procysteine sustained ciliary function and PKG and PKA responsiveness to β-agonists. However, BAL NO levels remained low despite antioxidant supplementation. We also determined that removal of alcohol from the drinking water for as little as 1 week restored ciliary function, but not PKG and PKA responsiveness to β-agonists. We conclude that dietary supplementation with NAC or procysteine protects against AICD. In addition, alcohol removal for 1 week restores cilia function independent of PKG and PKA activity. Our findings provide a rationale for the use of antioxidants to prevent damage to airway mucociliary functions in chronic alcohol-drinking individuals.
authors.affiliation: Pulmonary, Critical Care, Sleep, and Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5910, USA.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Simet
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Pavlik
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Sisson
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use*; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002923:Cilia / Q000187:drug effects / Q000502:physiology; D002925:Ciliary Motility Disorders / Q000139:chemically induced* / Q000178:diet therapy / Q000503:physiopathology / Q000517:prevention & control*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D019587:Dietary Supplements; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D051379:Mice; D017265:Procaterol / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D026361:Reactive Nitrogen Species / Q000032:analysis; D053778:Thiazolidines / Q000008:administration & dosage / Q000627:therapeutic use*; D014132:Trachea / Q000378:metabolism
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000975:Antioxidants; D026361:Reactive Nitrogen Species; D053778:Thiazolidines; D000431:Ethanol; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D011761:Pyrrolidonecarboxylic Acid; D000111:Acetylcysteine; C029536:2-oxothiazolidine-4-carboxylic acid; D017265:Procaterol
keywords: Alcohol; Ciliary beat frequency; Ciliary dysfunction; N-acetylcysteine; Nitric oxide; PKA; PKG; Procysteine