Browsing by Author "Halici Z."

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5-HT7 receptors as a new target for prostate cancer physiopathology and treatment: an experimental study on PC-3 cells and FFPE tissues
(2021-06-01) Cinar I.; Sirin B.; Halici Z.; Palabiyik-Yucelik S.S.; Akpinar E.; Cadirci E.
Prostate cancer (PCa) is one of the most common types of cancer seen among men worldwide. Previous studies have demonstrated that serotonin regulates cell proliferation, migration, and invasion in vitro; the presence of 5-HT receptors in cancer cells; and the role of serotonin in tumor development. The most recently discovered of these receptors is 5-HT7 but also least characterized receptors of serotonin. The aim of this study is to investigate the existence and possible role of 5-HT7 receptors in healthy and cancerous prostate tissues and also investigate effects of receptor agonists and antagonists on PC-3 cells to evaluate potential therapeutic effects. PC-3 cells were cultured and effects of 5-HT7 receptor agonist (LP-44) and antagonist (SB-269970) were evaluated on these cells. After proliferation analyses, relative expression of apoptotic markers and 5-HT7 receptor mRNA expression levels were determined through real-time PCR. Annexin V-FITC/PI double staining and Hoechst 33258 staining assay methods were applied to determine apoptosis. Additional PCR studies were performed on healthy and cancerous prostate tissue to see existence of receptors in human samples. The viability of PC-3 cells was decreased by SB-269970 after 48 and 72 h of incubation. However, LP-44 increased PC-3 cell proliferation at all time points. In 10-6 M SB-269970 treated PC-3 cells, there was significant increase in the expression of CAS-3 (4-fold), CAS-9 (2.5-fold), BAX (1.9-fold), and Tp-53 (4.8-fold) gene mRNA levels when compared to non-treated control group. Conversely, there was a significant decrease in NF-κB (2.9-fold) and 5-HT7 receptor (3.6-fold) mRNA expression in cells treated with SB-269970 when compared to control. SB-269970 that antagonized 5-HT7 receptors also induced apoptosis in Annexin V-FITC/PI double staining assay and Hoechst 33258 staining assays when compared with other groups. In human samples, 5-HT7 receptor mRNA expression was approximately 200-fold higher than that of heathy ones. In this study, for the first time, the 5-HT7 receptor antagonist SB-269970 has been shown to inhibit proliferation in PC-3 cells and to be associated with an apoptosis-inducing effect. These results suggest blocking 5-HT7 receptors can be a novel therapeutic target for the treatment of prostate cancer.
Does daily fasting shielding kidney on hyperglycemia-related inflammatory cytokine via TNF-α, NLRP3, TGF-β1 and VCAM-1 mRNA expression
(2021-11-01) Bilen A.; Calik I.; Yayla M.; Dincer B.; Tavaci T.; Cinar I.; Bilen H.; Cadirci E.; Halici Z.; Mercantepe F.
This study aimed to investigate the effects of blood glucose control and the kidneys' functions, depending on fasting, in the streptozotocin-induced diabetes model in rats via TNF-α, NLRP-3, TGF-β1 and VCAM-1 mRNA expression in the present study. 32 Wistar albino rats were allocated randomly into four main groups; H (Healthy, n = 6), HF (Healthy fasting, n = 6), D (Diabetes, n = 10), DF (Diabetes and fasting, n = 10). Blood glucose and HbA1c levels significantly increased in the D group compared to the healthy ones (p < 0.05). However, the fasting period significantly improved blood glucose and HbA1c levels 14 days after STZ induced diabetes in rats compared to the D group. Similar findings we obtained for serum (BUN-creatinine) and urine samples (creatinine and urea levels). STZ induced high glucose levels significantly up-regulated TNF-α, NLRP-3, TGF-β1 and VCAM-1 mRNA expression and fasting significantly decreased these parameters when compared to diabetic rats. Histopathological staining also demonstrated the protective effects of fasting on diabetic kidney tissue. In conclusion, intermittent fasting regulated blood glucose level as well as decreasing harmful effects of diabetes on kidney tissue. The fasting period significantly decreased the hyperglycemia-related inflammatory cytokine damage on kidneys and also reduced apoptosis in favor of living organisms.
Effect of Tocilizumab on Acinetobacter baumannii Lung Infection in an Immunosuppressed Rat Model
(2022-01-01) Celebi D.; Halici Z.; Celebi O.; Akgun N.; Keskin H.; Cinar I.; Halici I.; Cinisli K.T.; Yildirim S.
Our study aimed to investigate effect of tocilizumab on the lung tissue in the presence of Acinetobacter baumannii infection in immunosuppressed rats. A forty-eight female Wistar albino rats were divided equally into eight groups: Group 1: Healthy (H), Group 2: Immunosuppressed (IM), Group 3: Healthy rats given A. baumannii bacteria (H+BAC), Group 4: Immunosuppressed rats given A. baumannii bacteria (IM+BAC), Group 5: Healthy rats given tocilizumab (H+TCZ), Group 6: Immunosuppressed rats given tocilizumab (IM+TCZ), Group 7: Healthy rats given A. baumannii bacteria and tocilizumab (H+BAC+TCZ), Group 8: Immunosuppressed rats given tocilizumab and A. baumannii bacteria (IM+BAC+TCZ). Fourteen days after the immunosuppression of group 2, 4, 6 and 8 with hydrocortisone, group 3, 4, 7 and 8 were A. baumannii was dropped into the trachea. One hour after A. baumannii application, TCZ was administered to Groups 5, 6, 7 and 8. NF-κB, IL-6 and NLRP3 mRNA expressions were decreased in the IM group compared to the healthy group (P<0.05). Although NF-κB, IL-6 and NLRP3 mRNA expression decreased in the IM+TCZ group compared to the healthy group (P<0.05) NF-κB, IL-6 and NLRP3 mRNA expression increased in the H+TCZ group (P<0.05). Despite decreasing cytokines, A. baumannii has been shown to increase infection-related lung injury. This suggests that in patients currently or recently using steroids, tocilizumab may increase organ damage due to opportunistic infection.
Effects of simultaneous versus post exposure epigallocatechin-3-gallate treatment on aluminum induced neurotoxicity in rat hippocampus: A multi-approach study
(2023-03-01) Palabiyik-Yuceli̇k S.S.; Zeybek N.D.; Cinar I.; Akpinar E.; Bahador Zırh E.; Si̇pahi̇ H.; Halici Z.
Chronic aluminium(Al) exposure can affect the antioxidant and glutaminergic systems through N-methyl-D-aspartate receptors (NMDAR). This study was aimed to investigate the neurotoxic effect of Al through different mechanisms in rat hippocampus and to evaluate the protective role of epigallocatechin gallate (EGCG), a well-known antioxidant, with simultaneous administration of Al,as well as post-treatment after Al exposure.For this purpose, aluminum chloride(AlCl3) was administered simultaneously with two different EGCG doses for 8 weeks as the first part of the study.In the second part of the study, after 4 weeks of AlCl3 pre-administration, two different EGCG doses were also administered during four additional weeks as post-treatment.Al administration led to oxidative stress and increased acetylcholinesterase levels.NMDAR subunit mRNA expressions were down-regulated by Al, which was apparent in NMDAR1/2B subunits.Simultaneous EGCG treatment has shown a better neuroprotective effect in terms of these mechanisms and represents novel approach for the prevention of neurodegenerative diseases likely to be induced by Al.
Protective effect of luteolin on acute lung injury in a rat model of sepsis
(2021-01-01) Celebi D.; Aydin P.; Cinar I.; Kutlu Z.; Calik I.; Halici Z.; Bilici D.; Bayraktutan Z.
We investigated the effects of luteolin (LUT) treatment on acute lung injury caused by cecal ligation and puncture (CLP) induced septic rats. We also investigated the relation between LUT and the cytokines, interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α). LUT was administered 1 h after CLP surgery. Administration of LUT reduced the glutathione level and superoxide dismutase activity in rat lung tissues. We also found significant reduction of malondialdehyde following LUT treatment. LUT administration also reduced TNF-α and IL-10 mRNA expression in lung tissue. Histopathologic investigation of lung tissue supported our biochemical and molecular findings. Administration of LUT ameliorated lung injury in CLP induced septic rats owing to its antioxidant and anti-inflammatory properties.