We have previously shown that chronic alcohol ingestion causes profound oxidative stress within the airways of experimental animals as well as in otherwise healthy humans with significant alcohol use disorders (Holguin et al., 1998;Moss et al., 2000). As activation of the ARE through Nrf2 is critical to mount a healthy antioxidant response, our findings thus far in this study suggested that alcohol-induced zinc deficiency could be responsible at least in part for the airway oxidative stress we had first discovered in the alcoholic lung. Therefore, we next determined the effects of dietary zinc on the status of the important extracellular thiol pair, cysteine (Cys) and cystine (Cyss) in the airways of alcohol-fed rats. As shown in Figure 5, chronic alcohol ingestion significantly decreased (P<0.05) the relative ratio of cysteine to cystine (Cys/Cyss) in the lung lavage fluid of alcohol-fed rats as compared to the Cys/Cyss ratio in the lung lavage fluid of control-fed rats. In contrast, and consistent with its ability to induce Nrf2 and metallothionein gene expression, dietary zinc supplementation normalized (P>0.05) the Cys/Cyss ratio in the lung lavage fluid of alcohol-fed rats when compared to the lung lavage fluid of control-fed rats.
