Pulmonary effects of waterpipe generated smoke in adult diabetic rats

Abstract

Waterpipe smoking (WPS) is associated with pulmonary inflammation and DNA damage. Tobacco use among diabetic patients adds substantial clinical and public health burden. This study aims to investigate the combined pulmonary effects of diabetes and smoking. To achieve this goal, type 1 diabetes (T1D) was induced in adult male rats by Streptozotocin (65 mg/kg) injection. Rats were then exposed either to fresh air or WPS for one hour daily over five weeks (five days/week). Lung remodeling was evaluated by histology. Changes affecting inflammation, oxidative stress, apoptosis and survival pathways were characterized by real-time quantitative PCR and Western blot. Our findings showed that T1D was associated with pulmonary remodeling characterized by increases in lung weight/BW ratio, exacerbated by WPS, and elevated alveolar count. Both T1D and WPS exposure led to an accumulation of alveolar foamy macrophages and decreased alveolar septal thickness. Upregulation in the transcript levels of pro-inflammatory cytokine, TNF-α and anti-inflammatory marker, IL-10, were reported in diabetic lungs irrespective of WPS exposure. Moreover, diabetic lungs also displayed significant changes in the expression of mitochondrial complexes III and IV and antioxidant enzyme, SOD2, irrespective of the exposure condition. We also noted significant downregulation in the expression of caspases 3 and 9, p-P53/P53 ratio and JNK protein in diabetic lungs compared to control irrespective of the exposure condition. Lastly, diabetes and WPS exposure triggered significant decreases in EGFR expression. In conclusion, we show for the first time pulmonary remodeling and damages caused by the combined effects of T1D and smoking. Our findings highlight the pressing need for future better management of waterpipe consumption among patients with diabetes.