Impact of cigarette smoking on kidney inflammation and fibrosis in diabetic rats

Background: Cigarette smoking is a very common habit worldwide contributing to risk of kidney dysfunction and diabetes (DM). However, the mechanisms are unclear. Aim: The goal of the present study was to assess the effects of cigarette smoking on kidney oxidative stress, inflammation, and remodeling in streptozotocin (STZ) rat model of diabetes. Methods: Rats were randomized into control (intraperitoneal (i.p.) citrate buffer injection and exposure to fresh air), cigarette smoking (1 h daily for 6 d/week, citrate buffer), DM (single dose STZ 35 mg/kg i.p. and exposure to fresh air), and DM + smoking groups for a period of 4 weeks. Kidney biomarkers of inflammation, oxidative stress, and remodeling were measured. Results: A significant increase in kidney to body weight ratio was observed in diabetic groups. Diabetes but not smoking increased blood urea nitrogen levels without changes in creatinine levels. Kidney levels of thiobarbituric acid substances, nitrite, endothelin-1, and C-reactive protein were increased significantly in the DM + smoking groups. Smoking induced GSH expression and activity of superoxide dismutase. A significant increase in kidney fibrosis was observed in the DM + smoking group coupled with a similar increase in transforming growth factor beta. Protein levels of matrix metalloproteinase-2, (MMP-2), mitogen-activated protein kinases, and c-Jun N terminal kinase were elevated in Smoking and DM + smoking groups. Conclusion: Cigarette smoke might promote risk of kidney dysfunction in DM by augmentation of renal inflammation, oxidant radicals and fibrosis. The kidney promotes compensatory increase in MMP-2 in response to smoking probably to prevent pro-fibrotic factors induced-fibrosis.