A Zinc Chelate of Lysine/Glutamic Acid Reduces Alcohol-Induced Ciliary Dysfunction

Alcohol misuse is a known risk factor for pneumonia, and up to 50% of individuals who misuse alcohol are zinc deficient. Chronic alcohol misuse can lead to alcohol-induced ciliary dysfunction (AICD), preventing effective mucociliary clearance and protection against lung infection. Because zinc salts fail to alter AICD, we hypothesized a form of zinc (Zinpro Zinc LG) with enhanced cell uptake would protect against AICD. Human and mouse airway epithelial cells were treated with 50 mM ethanol for 1–24 h followed by the ciliostimulatory agents. Cilia beat frequency (CBF) and cAMP-dependent protein kinase (PKA) activity were assayed. Cyclic AMP or beta agonists stimulated a significant increase in CBF, but 24 h alcohol pretreatment resulted in the desensitization of the cilia to these agents. Pretreatment of cells with 1–10 µg/mL Zinpro Zinc LG prior to alcohol restored the cAMP cilia stimulation response. Zinpro Zinc LG alone produced no effects and was not toxic at <10 µg/mL. PKA activation was prevented in cells treated with alcohol for 24 h, but pretreatment with Zinpro Zinc LG prior to alcohol restored kinase activation. Zinpro Zinc LG prevented alcohol-stimulation of Protein Phosphatase-1, the regulator of PKA desensitization. These data demonstrate that the exposomal combination of alcohol and nutritional Zn deficiency could lead to an aberrant ciliary clearance response that may be prevented by effective zinc supplementation.