Protective effect of 5-HT7 receptor activation against glutamate-induced neurotoxicity in human neuroblastoma SH-SY5Y cells via antioxidative and antiapoptotic pathways

Serotonin exerts anti-inflammatory, antioxidant and antiapoptotic effects through 5-HT7 receptors. The present study determined the role of 5-HT7 receptors in glutamate-induced neurotoxicity by using human SH-SY5Y neuroblastoma cells. The cells were pretreated with different concentrations of 5-HT7 receptor agonist LP44 and antagonist SB269970 for 60 min, followed by treatment with glutamate. Cell proliferation was measured using xCELLigence system. Treatment with all the concentrations of LP44 significantly protected the cells from the toxic effects of glutamate after 24, 48 and 72 h. Although 5-HT7 receptor expression was significantly upregulated in glutamate-treated cells, it was downregulated in LP44-pretreated cells. Furthermore, LP44 treatment significantly decreased malondialdehyde levels and increased superoxide dismutase activities and glutathione levels. Moreover, LP44 treatment significantly decreased tumor necrosis factor alpha (TNF-a) levels and inhibited caspase 3 and caspase 9 mRNA expression. In contrast, SB269970 treatment exerted an insignificant effect on oxidative stress, inflammation and apoptosis. These findings suggest that exogenous stimulation of the 54-1T7 receptors may be protective in glutamate-induced neurotoxicity and that 5-HT7 receptor agonists can be used as therapeutic agents for preventing glutamate-induced neurological disorders.TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [112S627]This study is a part of Tugba Nurcan YUKSEL PhD thesis and is supported by TUBITAK (project number: 112S627). We would like to extend our special thanks to Yasin BAYIR and Abdulmecit ALBAYRAK for their contribution

Inhibiting renin angiotensin system in rate limiting step by aliskiren as a new approach for preventing indomethacin induced gastric ulcers

POLAT, Beyzagul/0000-0003-2042-5949; bayir, yasin/0000-0003-3562-6727; CADIRCI, ELIF/0000-0003-0836-7205; Albayrak, Abdulmecit/0000-0002-1062-1965; Karakus, Emre/0000-0002-0822-0054WOS: 000385368700028PubMed: 27645307Purpose: Previously blocking the renin angiotensin system (RAAS) has been effective in the prevention of gastric damage. Therefore, the aim of this study was to investigate the effects of aliskiren, and thus, direct renin blockage, in indomethacin-induced gastric damage model. Methods: Effects of aliskiren were evaluated in indomethacin-induced gastric damage model on Albino Wistar rats. Effects of famotidine has been investigated as standard antiulcer agent. Stereological analyses for ulcer area determination, biochemical analyses for oxidative status determination and molecular analyses for tissue cytokine and cyclooxygenase determination were performed on stomach tissues. in addition, to clarify antiulcer effect mechanism of aliskiren pylorus ligation-induced gastric acid secretion model was applied on rats. Results: Aliskiren was able to inhibit indomethacin-induced ulcer formation. It also inhibited renin, and thus, decreased over-produced Angiotensin-II during ulcer formation. Aliskiren improved the oxidative status and cytokine profile of the stomach, which was most probably impaired by increased Angiotensin II concentration. Aliskiren also increased gastroprotective prostaglandin E2 concentration. Finally, aliskiren did not change the gastric acidity in pylorus ligation model. Conclusion: Aliskiren exerted its protective effects on stomach tissue by decreasing inflammatory cytokines and oxidative stress as a result of inhibiting the RAAS, at a rate-limiting step, as well as its end product, angiotensin II. Aliskiren also significantly increased protective factors such as PGE2, but not affect aggressive factors such as gastric acidity. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Scientific Research Projects Commission of Ataturk University [ATAUNI-BAP-2013-234]This research was supported by Scientific Research Projects Commission of Ataturk University with project number ATAUNI-BAP-2013-234