Redox Modulation for the Treatment of Toluene Diisocyanates-Induced Lung Inflammation

Toluene diisocyanates (TDI) is a low-molecular-weight, high reactive chemical that widely used in industry for the production of polyurethane foams, vanish, paint, and isolation material.  Workers expose to TDI may cause the occupational asthma and show the mimic symptom as asthma.  Several mechanism of TDI-induced occupational asthma has been suggested, indicating that the pathogenesis may be more complex than other types of asthma.  One such candidate mechanism is oxidant stress.  In our previous investigation, we found that mice lacking leukocyte NADPH oxidase, which produce ROS after activation, may have less lung inflammation and airway hyperresponsiveness than wild-type (WT) mice after TDI exposure.  These results implicated that TDI exposure may induced oxidant stress in mice lung and cause lung inflammation (Liu et al., 2011).  Therefore, in this study we are testing the use of clinical antioxidant drug, N-acetylcysteine (NAC) to treat the mice which suffered from TDI.  In our experimental design, we treated the mice with NAC in three different methods：(1)Pre-treatment：The mice were pre-treated with NAC before the sensitization of TDI. (2)Continuously treatment：The mice were treated with NAC continuously during the sensitization of TDI. (3)Post-treatment：The mice were treated with NAC after the sensitization of TDI.  Then, we used MDA detection assay kit to determine the oxidant stress.  The histological analysis and cytokine profiles screening were performed to determine the inflammation level.  Last, we measured mice lung resistance and compliance with FinePointe Resistance and Compliance system.  The lung MDA production, which represents the oxidation level, were successfully reduced in each methods of NAC treatment, indicating that NAC treatment successfully reduced the oxidant stress which produced from TDI exposure.  Histopathological analysis showed, reduced level of inflammation, lung fibrosis and mucus production after NAC treatment in TDI-induced mice.  Moreover, TDI-treated mice with NAC treatment had better lung function parameters than the group without NAC treatment.  The treatment of NAC in three different methods could successfully cure the mice suffered from TDI exposure.  The mechanism of an antioxidant drug reveals a therapy for TDI- induced occupational asthma.

Liu, S.Y., Wang, W.Z., Yen, C.L., Tsai, M.Y., Yang, P.W., Wang, J.Y., Ho, C.Y., and Shieh, C.C. (2011). Leukocyte nicotinamide adenine dinucleotide phosphate-reduced oxidase is required for isocyanate-induced lung inflammation. The Journal of Allergy and Clinical Immunology 127, 1014-1023.