Protective Role Of Antioxidant Supplementation In Tobacco Smoke Toxicity At The Blood‐Brain Barrier

Abstract

Tobacco smoke (TS) is enriched in highly reactive oxidative species (e.g., hydrogen peroxide, peroxynitrate) which can damage the blood‐brain barrier (BBB) and trigger inflammatory events leading to the pathogenesis and progression of various neurological disorders. Physiological levels of antioxidants vitamin C and E are significantly reduced in smokers in fate of oxidative stress caused by TS exposure. We hypothesize that antioxidants can reduce the harmful effects of ROS‐dependent TS toxicity at the BBB.We exposed various in vitro BBB models to TS levels comparable to that found in chronic heavy smokers. Antioxidants supplementation of vitamin C and/or E at physiological concentration reduced TS‐induced vascular inflammatory response: release of proinflammatory cytokines from BBB endothelial cells and monocytes, release and activation of matrix metalloproteinases (MMPs), increased expression of vascular adhesion molecules. Furthermore, antioxidants reduced TS‐driven loss of BBB integrity and viability. Intravascular increase of nitric oxide (NO) by TS was also offset by antioxidants.Our results indicate that antioxidants can avert TS‐induced vascular pro‐inflammatory stimuli in vitro thus protecting the BBB. However, while antioxidants can reduce vascular oxidative stress, it might not be effective to counteract other teratogenic and pathophysiological stimuli induced by smoking.This work was supported by NIH/NIDA R01‐DA029121‐01A1 and Alternative Research Development Foundation (ARDF) to Dr. Luca Cucullo.