Diclofenac Recent reports revealed that CSE
Recent reports revealed that CSE affects the endothelial cells of various tissues like kidney, liver, heart including Diclofenac [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 . In addition, the CSE alters the basal and induced peroxidation of neuronal membrane lipids . Further, it enforces the oxidant stress, activation of degradation of membrane lipids with peroxidation and disturbs the endogenous antioxidant defense system [, , ]. Moreover, CSE also alters the glutathione biosynthetic pathways via modulatory action on glutathione peroxidase (GSH-Px) and glutathione-S-transferase (GST) activity [26,, ]. The direct attack of CSE also enhances the vascular dysfunction by releasing endothelial-derived contractility factors i.e., endothelin peptides . 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 . 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 . 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 . In addition, glutathione peroxidase is known to inhibit the formation of lipid peroxidative products i.e., malondialdehyde . Both, activity of NADPH oxidase and membrane lipid peroxidation are induced the cognitive dysfunction via reduction of glutathione and AChE activity levels [37,40].
The nootropic agents i.e., donepezil is also shown significant contribution in the attenuation of free radical generation, activation of endogenous antioxidant defense system like GSH and lipid peroxidation via its pleiotropic actions . In addition, donepezil showed the improvement of memory functions with the regulation of vascular integrity, endothelial functions, and neurovascular complications .
Conflict of interest
Introduction Thyroid cancer represents a good model for study of angiogenesis and cancer mechanisms because they are vascular and comprise a range of lesions with different degrees of malignancy . Papillary thyroid cancer is the most commonly diagnosed thyroid cancer, accounting for 80% of all cases . The overall prognosis is favorable with 10-year survival rates of more than 90%, but in some cases, the cancer behaves in an aggressive manner characterized by local recurrence and metastasis . Studies have shown that vascular endothelial growth factor (VEGF) has a pivotal role in the control of angiogenesis and impacts biological aggressiveness in thyroid cancers , , , , . However, VEGF is not the only factor involved in angiogenesis in cancer. Endothelins (ETs) are another group of factors that contribute to the control of angiogenesis and growth of cancer. The ETs are a family of genes that induce DNA synthesis and cellular growth in different tissues, primarily affecting vascular tone and angiogenesis . The ET axis is composed of three 21-amino-acid proteins, including ET-1, ET-2, and ET-3, paired with 2 G-protein–coupled receptors, ET receptor A (ETAR) and ET receptor B . In cancer, they have roles in the control of numerous factors in disease development and progression, including angiogenesis, stromal reaction, epithelial-mesenchymal transitions (EMTs), apoptosis, invasion, metastases, and drug resistance .