Browsing by Author "Cinar I."

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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.
Antipsychotics Induced Reproductive Toxicity by Stimulating Oxidative Stress: A Comparative in Vivo and in Silico Study
(2023-01-01) Dincer B.; Bulent Yazici A.; Cinar I.; Toktay E.; Selli J.; Cadirci E.; Bayraktutan Z.; Yazici E.
The pathophysiological mechanism behind the link between antipsychotic drugs and sexual dysfunction is still unknown. The goal of this research is to compare the potential effects of antipsychotics on the male reproductive system. Fifty rats were randomly assigned into the five groups indicated: Control, Haloperidol, Risperidone, Quetiapine and Aripiprazole. Sperm parameters were significantly impaired in all antipsychotics-treated groups. Haloperidol and Risperidone significantly decreased the level of testosterone. All antipsychotics had significantly reduced inhibin B level. A significant reduction was observed in SOD activity in all antipsychotics-treated groups. While GSH levels diminished, MDA levels were rising in the Haloperidol and Risperidone groups. Also, the GSH level was significantly elevated in the Quetiapine and Aripiprazole groups. By causing oxidative stress and altering hormone levels, Haloperidol and Risperidone are damaging to male reproductivity. This study represents useful starting point for exploring further aspects of the underlying mechanisms reproductive toxicity of antipsychotics.
Apoptosis-inducing activity and antiproliferative effect of gossypin on pc-3 prostate cancer cells
(2021-01-01) Cinar I.
Aim: The rapid growth, morbidity and mortality of prostate cancer, and the lack of effective treatment have attracted great interest of researchers to find novel cancer therapies aiming at the effect of gossypin on cell proliferation and apoptosis of PC-3 cells. Methods: The effect of gossypin on cell viability was determined using MTT assay at 5-100µg/ml and cisplatin (50µM) in a time-dependent manner in PC-3 cell lines. The expression levels of caspase-3 (CASP3) and caspase-9 (CASP9) for apoptosis and Nuclear Factor Kappa B (NFKB1) for survival, inflammation, and growth were evaluated by real-time PCR. Hoechst staining was used to analyze apoptosis. Results: Gossypin showed an anti-proliferative effect on PC3 cell line in a time-and dose-dependent manner. In addition, gossypin led to a significant increase in apoptosis genes (CASP3, CASP9) when compared to control while it caused a decrease in the level of NFKB1, which is accepted as apoptosis inhibitor (p<0.05) (cisplatin-like). Gossypin 50 and 100µM significantly induced apoptotic mechanism in PC-3 cells. However, no apoptotic or commonly stained nuclei have been observed in control group cells. Conclusion: The results indicated that gossypin can be defined as a promising anticancer agent for PC-3 human prostate cancer cell line.
Apoptosis-Inducing Activity and Antiproliferative Effect of Gossypin on PC-3 Prostate Cancer Cells.
(2020-07-21) Cinar, Irfan; Cinar, I
The rapid growth, morbidity and mortality of prostate cancer, and the lack of effective treatment have attracted great interest of researchers to find novel cancer therapies aiming at the effect of gossypin on cell proliferation and apoptosis of PC-3 cells.
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.
Evaluation of the protective effects of gossypin for ischemia/reperfusion injury in ovary tissue
(2022-03-01) Dincer B.; Cinar I.; Yayla M.; Toktay E.
Aim: Ovarian ischemia–reperfusion (I/R) injury is a serious gynecological condition that affects women of reproductive age and reduces ovarian reserve. Management of I/R injury with detorsion causes reperfusion damage, in which oxidative stress plays a central role. This study aimed to investigate whether the gossypin (GOS) with antioxidant properties, a flavonoid, has beneficial effects on the biochemical, molecular, and histopathological aspects of ovarian I/R injury. Methods: Thirty-three female Balb/c mice were randomly divided into five groups as follows: Healthy (Sham-operated control group), I/R (IR group), I/R + GOS 5 (I/R with GOS 5 mg/kg), I/R + GOS 10 (I/R with GOS 10 mg/kg), and I/R + GOS 20 (I/R with GOS 20 mg/kg). This was followed by 3 h of ischemia and subsequent reperfusion for 3 h after detorsion was exposed. GOS was injected 2 h before reperfusion. Results: IL-1β, IL-6, TNF-α, NF-κB, and CASP-3 mRNA expressions, SOD (superoxide dismutase) activity, GSH (glutathione), and MDA (malondialdehyde) levels, and histopathological changes were evaluated in ovarian tissue. Histological examination indicated that treatment of ovarian I/R injury with GOS led to the improvement of ovarian tissue, which was accompanied by an increase in SOD activity and GSH level and a decrease in MDA level, NF-κB, TNF-α, IL-1β, and IL-6 expressions. GOS was also corrected by reducing the elevated expression of CASP-3 as apoptosis-change marker. Conclusion: These findings indicate that the treatment of GOS may be useful as a conservative approach to reverse I/R injury via amelioration of oxidative stress parameters and histopathological scores, attenuation of inflammation, and the suppression of apoptosis.
Gossypin mitigates oxidative damage by downregulating the molecular signaling pathway in oleic acid-induced acute lung injury
(John Wiley and Sons Ltd, 2023) Dincer B.; Cinar I.; Erol H.S.; Demirci B.; Terzi F.
One of the leading causes of acute lung injury, which is linked to a high death rate, is pul-monary fat embolism. Increases in proinflammatory cytokines and the production of freeradicals are related to the pathophysiology of acute lung injury. Antioxidants that scav-enge free radicals play a protective role against acute lung injury. Gossypin has beenproven to have antioxidant, antimicrobial, and anti-inflammatory properties. In this study,we compared the role of Gossypin with the therapeutically used drug Dexamethasonein the acute lung injury model caused by oleic acid in rats. Thirty rats were divided intofive groups; Sham, Oleic acid model, Oleic acid+Dexamethasone (0.1 mg/kg), Oleic acid+Gossypin (10 and 20 mg/kg). Two hours after pretreatment with Dexamethasone orGossypin, the acute lung injury model was created by injecting 1 g/kg oleic acid into thefemoral vein. Three hours following the oleicacid injection, rats were decapitated. Lungtissues were extracted for histological, immunohistochemical, biochemical, PCR, andSEM imaging assessment. The oleic acid injection caused an increase in lipid peroxidationand catalase activity, pathological changes in lung tissue, decreased superoxide dismu-tase activity, and glutathione level, and increased TNF-α,IL-1β, IL-6, and IL-8 expression.However, these changes were attenuated after treatment with Gossypin and Dexameth-asone. By reducing the expression of proinflammatory cytokines and attenuating oxida-tive stress, Gossypin pretreatment provides a new target that is equally effective asdexamethasone in the treatment of oleic acid-induced acute lung injury
In Vivo and In Vitro Cardioprotective Effect of Gossypin Against Isoproterenol-Induced Myocardial Infarction Injury
(2022-01-01) Cinar I.; Yayla M.; Tavaci T.; Toktay E.; Ugan R.A.; Bayram P.; Halici H.
The aim of the study was to examine the protective effects and possible mechanism of gossypin against isoproterenol (ISO)-mediated myocardial damage in vivo and H9c2 cell damage in vitro. H9c2 cells were categorized into five groups. Viability was evaluated with MTT and LDH release in H9c2 cells. Apoptotic parameter analysis was performed with cytochrome c (Cyt-c), caspase-3 (CASP-3), and BCL2/Bax mRNA expression levels. In vivo, gossypin was administered orally to mice at doses of 5, 10, and 20 mg/kg for 7 days. ISO groups were injected with isoproterenol (150 mg/kg) subcutaneously (on 8th and 9th) for 2 days. Afterward, lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) levels and Troponin-I (Tn-I) amount from their serum, oxidative stress parameters superoxide dismutase (SOD) activity, glutathione (GSH) and malondialdehyde (MDA) levels, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1 β), and NF-kB mRNA expression levels with inflammatory markers from heart tissue were evaluated. In addition, IL-1B, BCL-2, and cas-3 immunohistochemical staining was performed from heart tissue and TNF-a level was measured by ELISA method. Administration of Gossypin protected the cells by dose-dependent, eliminating the reduced cell viability and increased LDH release of ISO in H9c2 cells. In mice serum analyses, increased LDH, CK-MB levels, and Tn-I levels were normalized by gossypin. ISO administration in heart tissue is regulated by gossypin with increased SOD activity, GSH amount, TNF-α, IL-6, IL-1β, and NF-kB mRNA expression levels and decreased MDA amount. Overall, the present results demonstrated that gossypin has a potential cardioprotective treatment for ischemic heart disease on in vivo and in vitro.
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.
Role of endothelin 1 on proliferation and migration of human MCF-7 cells
(2020-10-01) Cinar I.; Yayla M.; Celik M.; Bilen A.; Bayraktutan Z.
Objective: The aim of this study was to explore the role of endothelin 1 (ET-1) in human breast cancer proliferation and migration and antagonism of endothelin receptor A (ETAR) and endothelin receptor B (ETBR) by using the non-selective dual ETA/ETB receptor antagonist bosentan and determine its anti-proliferative, anti-metastatic, and apoptotic effects demonstrated by nuclear factor kappa B (NF-kB), vascular endothelial growth factor (VEGF), Caspase 3 and Caspase 9 expression on endothelin-induced proliferation of MCF-7 cell line in vitro. Materials and Methods: A total of 8,000 cells were seeded into e-plates 24 hours after the cells were incubated with or without 10-4 M BOS (1 hour before ET-1 treatment); 10-7, 10-8, and 10-9 M ET-1 for 1-4 days. Results: Whether ET-1 is present or not in the tumor area, bosentan exerts anti-proliferative effect on breast cancer. However, ET-1 and bosentan group showed important inhibitory effect on tumor migration compared to bosentan alone, which can be attributed to increased activity of ET-1 axis in the presence of ET-1. The imbalance among the NF-kB, caspases, and VEGF, which are predictive factors of carcinogenesis significantly improved after bosentan administration. Conclusion: Our study definitely demonstrated ET-1 and its critical role in cancer progression with apop-totic and anti-apoptotic pathways (NF-κB) and VEGF expression, and migration analyses were also per-formed. The second major finding was that bosentan inhibited ET-1-mediated effects on tumor proliferation and migration.
Unlocking Synergistic Potential: Agomelatine Enhances the Chemotherapeutic Effect of Paclitaxel in Breast Cancer Cell Through MT1 Melatonin Receptors and ER-alpha Axis
(John Wiley and Sons Inc, 2023) Dincer B.; Yildiztekin G.; Cinar I.
This study investigates the potential of agomelatine (AGO), a synthetic melatoninergic drug, in combination with paclitaxel (PTX) for the treatment of breast cancer. The effects of AGO, PTX and melatonin (MTN) on breast cancer cell viability were investigated, focusing on the role of MT1 receptors. Cell viability and gene expression were analyzed in MCF-7 and MDA-MB-231 breast cancer cell experiments. The results show that AGO has cytotoxic effects on breast cancer cells similar to MTN. Combining AGO and MTN with PTX showed synergistic effects in MCF-7 cells. The study also reveals differences in the molecular mechanisms of breast cancer between estrogen-positive MCF-7 cells and estrogen-negative MDA-MB-231 cells. Combination with AGO and PTX affects apoptosis-associated proteins in both cell types. The findings suggest that AGO, combined with PTX, may be a promising adjuvant therapy for breast cancer and highlight the importance of MTN receptors in its mechanism of action.