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  • Küçük Resim Yok
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    Effect of PDE 5 Inhibitor-Avanafil on Renal Ischemia/Reperfusion Injury in Rats
    (Galenos Publ House, 2023) Yuksel, Tugba Nurcan; Halici, Zekai; Kaya, Cihangir; Bozkurt, Ayse; Tavaci, Taha; Civelek, Maide Sena; Ozdemir, Bengul
    Aim: Renal ischemia-reperfusion injury (RI/RI) damages many organs, especially the kidney. Phosphodiesterase (PDE) 5 inhibitors has antioxidant and anti-inflammatory effects. Avanafil (AVA) is a second-generation PDE 5 inhibitor with greater PDE isoform selectivity. The aim of this study is to investigate the effects of AVA on RI/RI in rats. Materials and Methods: Forty rats were randomly divided into five groups (n=8): Sham; AVA 10; RI/RI; RI/RI + 5 mg/kg AVA, and RI/RI + 10 mg/ kg AVA. RI/RI in rats was established by clamping renal artery. An acute surgical experiment was performed for the induction of renal ischemia for 45 min by renal artery clamping followed by reperfusion for 24 h. Kidney tissues were investigated biochemically [malondialdehyde (MDA) and glutathione (GSH) with ELISA], molecularly [relative quantification of IL-113, nuclear factor-kappa B (NF-KB), and tumor necrosis factor-alpha (TNF-a) mRNA gene expression with qRT-PCR], and histopathologically (staining with Harris hematoxylin and eosin Y). Results: AVA administration ameliorated disturbances in MDA and GSH levels caused by RI/RI. AVA treatment improved the increase in the mRNA expressions of IL-113, NF-KB, and TNF-a in kidney tissues induced ischemia/reperfusion injury. AVA administration ameliorated histopathologic injury in kidney tissues caused by renal ischemia reperfusion. Moreover, the values closest to those of the sham group were obtained by administering 10 Conclusion: AVA administration improved renal ischemia/reperfusion-induced tissue injury by alleviating oxidative stress and inflammatory cascades that could be important in ischemia-reperfusion injury. These findings may provide a mechanistic basis for using AVA to treat RI/RI.
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    Neuroprotective effect of roflumilast under cerebral ischaemia/reperfusion injury in juvenile rats through NLRP-mediated inflammatory response inhibition
    (Wiley, 2021) Keskin, Halil; Keskin, Filiz; Tavaci, Taha; Halıcı, Hamza; Yüksel, Tuğba Nurcan; Özkaraca, Mustafa; Halıcı, Zekai
    This study aims to investigate the protective effect of roflumilast, a phosphodiesterase (PDE)-4 enzyme inhibitor, and demonstrate its possible role in the development prevention of cerebral ischemia/reperfusion injury (CI/RI) after stroke induced by carotid artery ligation in juvenile rats. The rats were randomly divided into five groups: healthy group without any treatment, healthy group administered with 1 mg/kg roflumilast, CI group not administered with roflumilast, CI group administered with 0.5 mg/kg roflumilast, and CI group administered with 1 mg/kg roflumilast. In the CI groups, reperfusion was achieved 2h after ischemia induction; in the roflumilast groups, this drug was intraperitoneally administered immediately after reperfusion and at the 12(th) hour. At the end of 24h, the rats were sacrificed and their brain tissues removed for examination. The mRNA expressions obtained with real-time PCR of IL-1 beta, TNF-alpha, and NLRP3 significantly increased in the CI/RI-induced groups compared with the control group, and this increase was significantly lower in the groups administered with roflumilast compared with the CI/RI-induced groups. Moreover, ELISA revealed that both IL-1 beta and IL-6 brain levels were significantly higher in the CI/RI-induced groups than in the controls. This increase was significantly lower in the groups administered with roflumilast compared with the CI/RI-induced groups. Histopathological studies revealed that the values closest to those of the healthy group were obtained from the roflumilast groups. Nissl staining revealed that the Nissl bodies manifested normal density in the healthy and roflumilast-administered healthy groups, but were rare in the CI/RI-induced groups. Roflumilast treatment increased these decreased Nissl bodies with increasing doses. Observations indicated that the Nissl body density was close to the value in the healthy group in the CI/RI-induced group administered with 1 mg/kg roflumilast. Overall, roflumilast reduced cellular damage caused by CI/RI in juvenile rats, and this effect may be mediated by NLRP3.