Abstract
BackgroundSmoking (TS) and recently e-cigarettes (EC) vaping, have been associated with vascular endothelial dysfunction primarily relevant to oxidative stress, exposure to nicotine, and smoking-induced inflammation. It is accepted that both EC and TS enhance glucose intolerance and the risk of developing type-2 diabetes mellitus which is also one of the causes of blood–brain barrier (BBB) damage and the higher risk of cerebrovascular diseases. Recent studies have shown how Metformin, the first common antidiabetic drug, can protect the BBB integrity through enhancement of nuclear factor erythroid 2-related factor (Nrf2) activity. Herein, we investigated the role of rosiglitazone (RSG; family of thiazolidinedione class used oral anti-diabetic drug) in TS/EC-induced BBB impairment.ResultsAlthough the exact mechanism of RSG is not fully understood, previous studies have revealed that RSG can promote counteractive protective mechanisms primarily associated with the enhancement of Nrf2 activity through activation of the peroxisome proliferator-activated receptor gamma. In line with these findings, our results show an increased expression of PPARy by RSG, enhancement of Nrf2 activity and BBB protection against TS/EC exposure including reduced inflammation, oxidative stress, tight junction downregulation and loss of BBB integrity.ConclusionsRSG could be considered as a promising therapeutic potential to prevent TS/EC induced cerebrovascular dysfunction and possibly other xenobiotic substances which may impact the BBB via oxidative stress-mediated effects. However, additional in vivo studies and clinical setting will be needed to validate our results and assess the full extent of RSG protective effects.
Highlights
Smoking (TS) and recently e-cigarettes (EC) vaping, have been associated with vascular endothelial dysfunction primarily relevant to oxidative stress, exposure to nicotine, and smoking-induced inflammation
The content of Tobacco smoke (TS) and EC is associated with vascular endothelial dysfunction in a dose-dependent and causative manner [8, 9] which is primarily relevant to the content of reactive oxygen species (ROS), nicotine [3, 9], oxidative stress (OS) [10,11,12,13], blood–brain barrier (BBB) impairment [14, 15] and driven inflammation [16] leading to various cerebrovascular and neurological disorders including stroke [5, 17], amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) [18]
We found that RSG have protective effects through the activation of nuclear factor erythroid 2-related factor (Nrf2), and the antioxidant effect of RSG leads to the reduction of TS/EC-induced oxidative stress and loss of BBB integrity which might be through peroxisome proliferator-activated receptor gamma (PPARγ)-dependent or PPARγ-independent pathways
Summary
Smoking (TS) and recently e-cigarettes (EC) vaping, have been associated with vascular endothelial dysfunction primarily relevant to oxidative stress, exposure to nicotine, and smoking-induced inflammation. The content of TS and EC is associated with vascular endothelial dysfunction in a dose-dependent and causative manner [8, 9] which is primarily relevant to the content of reactive oxygen species (ROS), nicotine [3, 9], oxidative stress (OS) [10,11,12,13], blood–brain barrier (BBB) impairment [14, 15] and driven inflammation [16] leading to various cerebrovascular and neurological disorders including stroke [5, 17], amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) [18]. We found that RSG have protective effects through the activation of Nrf, and the antioxidant effect of RSG leads to the reduction of TS/EC-induced oxidative stress and loss of BBB integrity which might be through PPARγ-dependent or PPARγ-independent pathways
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