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  • Cigarette smoking plays a chief risk

    2020-07-31

    Cigarette smoking plays a chief risk factor in various neurovascular complications [21]. The mechanism of CSE induced neurovascular complications are activates the immune cells like glial cells, dendritic cells, mast cells and so on [22]. In addition, it also alters the cellular metabolic pathways lead to generate abundant free radicals via mitochondrial dysfunction. Further, it alters the cytosolic ion concentration via open the ion channels and enhances the excitatory amino acid receptors functions [23]. These actions intensified the long-term-potentiation via neuronal firings [24]. Subsequently, it alters the nuclear, mitochondria, endoplasmic reticulum and cellular membrane proteins (lipid peroxidation) and minimizes the reduced glutathione level [25]. The exposure of cigarette smoke and their condensate has additional effect i.e., alteration of neurotransmitters including Penicillin G Sodium levels via modulation of acetylcholinesterase (AChE) activity [[26], [27]]. The raising AChE activity level by CSE induces memory dysfunction [26]. The exact molecular mechanism of CSE in AChE activity is not clear yet. However, CSE alters the amyloid peptide pathway with the interference of AChE activity leads to alleviating the Alzheimer\'s disease [[28], [29]]. Recent reports revealed that CSE affects the endothelial cells of various tissues like kidney, liver, heart including brain [26,30]. The damage of brain endothelial cells enhances the progress of cognitive dysfunction due to the accumulation of toxic free bio-radicals and activation of inflammatory cytokines [26]. In addition, the CSE alters the basal and induced peroxidation of neuronal membrane lipids [31]. Further, it enforces the oxidant stress, activation of degradation of membrane lipids with peroxidation and disturbs the endogenous antioxidant defense system [[32], [33], [34]]. Moreover, CSE also alters the glutathione biosynthetic pathways via modulatory action on glutathione peroxidase (GSH-Px) and glutathione-S-transferase (GST) activity [26,[34], [35]]. The direct attack of CSE also enhances the vascular dysfunction by releasing endothelial-derived contractility factors i.e., endothelin peptides [36]. Endothelin peptides activate the endothelin-1 and endothelin-2 receptors. The endothelin-1 receptor has a role in the progress of neurodegeneration via reorganization of blood-brain barrier and neuroimmune function. The administration of selective endothelin 1 receptor antagonist i.e., ambrisentan attenuates the l-methionine induced cognitive dysfunctions [37]. The present study reports also shown the administration of ambrisentan ameliorates the CSE induced the neurotoxic effect. Clinically, it\'s also proved as neuroprotective agent for the neurovascular complication due to its regulatory property of blood-brain barrier and vascular integrity [38]. Furthermore, CSE induced vascular damage has been ameliorated by ambrisentan via regulation of NADPH oxidases [34,37]. The NADPH oxidases are the key factors for generation of univalent oxygen anion (superoxide), cytokines, and acceleration of AChE activity in brain neuronal cells. The treatment of endothelin receptor antagonists like ambrisentan exerts the anti-inflammatory actions by the reduction of leukocyte-endothelium interactions and attenuates the dysfunction of the endothelial cell barrier. Ambrisentan also attenuates the free radicals associated peroxidation of neuronal lipid membranes [37]. In addition, glutathione peroxidase is known to inhibit the formation of lipid peroxidative products i.e., malondialdehyde [39]. Both, activity of NADPH oxidase and membrane lipid peroxidation are induced the cognitive dysfunction via reduction of glutathione and AChE activity levels [37,40].