| Chronic obstructive pulmonary disease (COPD) is a persistent obstruction of airways in the lungs due to the narrowing of the passage ways. Cigarette smoking is responsible for approximately 80-90% of COPD-related deaths. Cigarette smoke contains over 4000 chemicals, including carcinogens, strong electrophiles and other toxins. The current study was undertaken to determine the role of cigarette smoke in the development of mitochondrial dysfunction due to impairment of the energy-redox axis. Rat lung epithelial cell cultures (RLE-6TN cell line) and male A/J mice were used to study the effects of cigarette smoke extract (CSE) or cigarette smoke (CS), respectively. The effects of individual constituents of CSE like acrolein and nitric oxide on cell viability and redox status of the cell was also assessed. We have adapted a method to prepare cigarette smoke extract in our laboratory by smoking 4 cigarettes in 20 ml of serum free F-12 media. Our data indicate that treatment of RLE-6TN cells with doses less than 2.5% CSE for 4 h, and whole body smoke exposure for 2 weeks in A/J mice lead to an increase in the NADPH/NADP+ ratio with no change in the NADH/NAD+ ratio as measured by HPLC. At 24 h, a decrease in both NADPH/NADP+ and NADH/NAD + ratios, indicate of an initial compensatory response to cigarette smoke. This increase in NADPH was found to be because of the increased activity of the pentose phosphate pathway. The other redox couple of GSH/GSSG was also shown to increase. |
