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.

中文翻译：

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评估罗格列酮对电子烟/烟草烟雾引起的血脑屏障损伤的保护作用

背景吸烟（TS）和最近的电子烟（EC）与血管内皮功能障碍有关，主要与氧化应激、接触尼古丁和吸烟引起的炎症有关。人们普遍认为，EC和TS都会增加葡萄糖不耐受和患2型糖尿病的风险，这也是血脑屏障（BBB）损伤和脑血管疾病风险增加的原因之一。最近的研究表明，第一种常见的抗糖尿病药物二甲双胍可以通过增强核因子红细胞 2 相关因子 (Nrf2) 的活性来保护血脑屏障的完整性。在此，我们研究了罗格列酮（RSG；噻唑烷二酮类口服抗糖尿病药物家族）在 TS/EC 引起的 BBB 损伤中的作用。结果虽然 RSG 的确切机制尚不完全清楚，但先前的研究表明 RSG 可以促进反作用保护机制主要与通过激活过氧化物酶体增殖物激活受体γ来增强Nrf2活性有关。与这些发现一致，我们的结果表明，RSG 增加了 PPARγ 的表达，增强了 Nrf2 活性，并增强了 BBB 对 TS/EC 暴露的保护，包括减少炎症、氧化应激、紧密连接下调和 BBB 完整性丧失。具有预防 TS/EC 诱导的脑血管功能障碍以及可能通过氧化应激介导的作用影响 BBB 的其他异生物质的有前途的治疗潜力。然而，需要额外的体内研究和临床环境来验证我们的结果并评估 RSG 保护作用的全部范围。