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    18?-glycyrrhetinic acid attenuates global cerebral ischemia/reperfusion-induced cardiac damage in C57BL/J6 mice
    (Univ Sao Paulo, Conjunto Quimicas, 2022) Turkmen, Nese Basak; Yuce, Hande; Taslidere, Asli; Sahin, Yasemin; Ayhan, Idris; Unuvar, Songuel; Ciftci, Osman
    The aim of the present study is to investigate the cardioprotective effects of 1813-glycyrrhetinic acid (1813-GA) against oxidative and histological damage caused by global cerebral ischemia/ reperfusion (I/R) in C57BL/J6 mice. All male mice (n:40) were randomly divided into four groups: (1) sham-operated (Sham), (2) I/R, (3) 1813-GA, and (4) 1813-GA+I/R. Ischemia was not applied to the sham and 1813-GA groups. In the I/R group, the bilateral carotid arteries were clipped for 15 min to induce ischemia, and the mice were treated with the vehicle for 10 days. In the 1813-GA group, the mice were given 1813-GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the 1813-GA+I/R group, the ischemic procedure performed to the I/R model was applied to the animals and afterwards they were intraperitoneally (i.p.) treated with 1813-GA (100 mg/kg) for 10 days. It was found that global cerebral I/R increased TBARS levels and decreased antioxidant parameters. The 1813-GA treatment decreased the level of TBARS and increased GSH, GPx, CAT, SOD activities. Also, the control group cardiac tissue samples were observed to have a normal histological appearance with the Hematoxylin-Eosin staining method. Histopathological damage was observed in the heart tissue samples belonging to the I/R group. The 1813-GA treatment ameliorates oxidative and histological injury in the heart tissue after global ischemia reperfusion, and may be a beneficial alternative treatment.
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    Beneficial effects of taurine on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced oxidative and histopathological damage in the heart tissue of rats
    (Sage Publications Inc, 2026) Ciftci, Osman; Kaplan, Munevver Nazlican; Basak Turkmen, Nese; Cetin, Asli; Ciftci, Bedriye; Ayhan, Idris
    This study investigated the protective effects of taurine against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced cardiotoxic damage in rats. Adult male Wistar rats (250-300 g) were randomly assigned to four groups (n = 8 per group): Control, TCDD, TAU, and TCDD + TAU. TCDD (2 mu g/kg/week) and/or taurine (200 mg/kg/day) were administered via gavage for 30 days. Following the experimental period, heart tissue samples were collected for analysis. Oxidative stress parameters, including thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) activity, and glutathione (GSH) levels, were assessed using biochemical methods. Histopathological and immunohistochemical evaluations of cardiac tissue were also performed. The TCDD group showed significantly increased TBARS levels (p < 0.05) and decreased SOD activity and GSH levels (p < 0.001) compared with the Control group. In contrast, taurine co-administration significantly increased SOD activity and GSH levels while reducing TBARS levels relative to the TCDD group. Moreover, TCDD exposure induced marked histopathological alterations in heart tissue, whereas taurine co-administration attenuated these structural alterations. Immunohistochemical findings indicated that taurine attenuated TCDD-induced apoptosis by reducing caspase-3 activation. Overall, taurine effectively mitigated TCDD-induced oxidative stress, histopathological damage, and apoptotic signaling in cardiac tissue, suggesting that taurine co-administration may exert protective effects against TCDD-induced cardiotoxicity.
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    Hesperidin Mitigates Bleomycin-Induced Testicular and Spermatological Damage in Rats
    (Wiley, 2025) Ayhan, Idris; Turkmen, Nese Basak; Alan, Saadet; Aydin, Muhterem; Ciftci, Osman
    Bleomycin (BLM), a chemotherapeutic agent commonly used in cancer treatment, is associated with oxidative stress and testicular toxicity, leading to impaired reproductive health. Hesperidin (HES), a citrus-derived flavonoid with strong antioxidant properties, has the potential to counteract these adverse effects. This study aimed to evaluate the protective effects of HES against the reproductive toxicity induced by BLM, focusing on oxidative stress, sperm characteristics and histological changes in the male reproductive system. Thirty-two rats were divided into four groups: Control, BLM, HES and BLM + HES. BLM was administered intraperitoneally at 10 mg/kg twice a week, while HES was given orally at 50 mg/kg/day for 30 days. The findings revealed that BLM induced significant oxidative stress by promoting lipid peroxidation and impairing antioxidant defence mechanisms in the testis. Additionally, BLM treatment caused a marked decline in sperm motility, an increase in abnormal sperm rates and severe histopathological damage in testicular tissue. However, co-administration of HES significantly mitigated these adverse effects by improving oxidative balance, restoring sperm quality and reducing histopathological injuries. In conclusion, HES demonstrated potential in alleviating BLM-induced reproductive toxicity, suggesting its therapeutic role in protecting against chemotherapy-induced male infertility.
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    Investigation of protective effect of ellagic acid in phthalates-induced reproductive damage
    (Taylor & Francis Ltd, 2022) Turkmen, Nese Basak; Ayhan, Idris; Taslidere, Asli; Aydin, Muhterem; Ciftci, Osman
    Phthalates that people are exposed to every day are toxic carcinogenic chemicals with proven harmful effects on growth and reproduction. Ellagic acid (EA) is a polyphenol derivative known for its antioxidant properties. We hypothesized that the possible reproductive damage mechanism of phthalates is oxidative attack and ellagic acid could have a protective effect against radical forms in the body through its antioxidant properties. Thirty-two male rats were randomly divided into 4 groups, with 8 rats in each. Phthalate (DBP) was administered intraperitoneally and EA acid through gastric oral gavage (phthalate group 500 mg/kg/day DBP; EA group 2 mg/kg/day ellagic acid; the treatment group 500 mg/kg/day DBP and 2 mg/kg/day EA). The vehicle of DBP and EA, carboxymethyl cellulose was administered to control group. At the end of 4 weeks the testis tissue samples were taken under mild anesthesia. Tissue malondialdehyde, antioxidant parameters, sperm motility, sperm density and abnormal spermatozoon ratios were determined. Analysis was performed with One Way ANOVA test using SPSS 12.0 program. As a result; it has been shown that DBP causes oxidative damage by increasing the malondialdehyde level and decreasing antioxidant parameters, increased abnormal sperm rate and decreased sperm motility and concentration and histopathological damage so this damage is inhibited by the antioxidant activity of ellagic acid.
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    The Novel Synthesized Pyridazinone Derivates Had the Antiproliferative and Apoptotic Effects in SHSY5Y and HEP3B Cancer Cell Line
    (Bentham Science Publ Ltd, 2018) Ciftci, Osman; Ozdemir, Zeynep; Acar, Ceren; Sozen, Mert; Basak-Turkmen, Nese; Ayhan, Idris; Gozukara, Harika
    Background: Brain cancer (neuroblastoma) and liver cancer (hepatocellular carcinoma) are common cancer types among others worldwide which do not have a radical treatment and cure. Objective: In the current study, five novel pyridazinone derivates bearing benzelhydrazone moiety at second position were synthesized and evaluated for their cytotoxic activity against neuroblastoma and hepatocellular carcinoma (SHSY5Y and HEP3B) and human fibroblast (HF) cell lines. The aim of the current study is to identify antiproliferative activity of five novel pyridazinone derivates against neuroblastoma and hepatocellular carcinoma (SHSY5Y and HEP3B) and human fibroblast (HF) cell lines. Method: The compounds were synthesized by the reacting 6-[4-(phenyl/4-chlorophenyl)piperazine-1yl]-3(2H)-pyridazinone-2-yl acetohydrazide with benzaldehyde in ethanol. The in vitro antiproliferative activities were determined with MTT assay. Bax, Bcl-2 and Casp3 gene expression levels were detected with RT-PCR analyses. Results: The lowest IC50 was observed for compound 4 in SHSY5Y and HEP3B cells. Apoptosis increased in cancer cells which was shown by changes inBax, Bcl-2 and Casp3 gene expression levels with 1-5 compound therapy. Conclusion: Novel pyridazinone derivates might be promising agents as new chemotherapeutic candidates in brain and liver cancer.
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    Protective Effect of Nerolidol on Paclitaxel-Induced Reproductive Toxicity in Rats: Oxidative Stress and Inflammation
    (Wiley, 2025) Ayhan, Idris; Turkmen, Nese Basak; Taslidere, Asli; Aydin, Muhterem; Ciftci, Osman
    Paclitaxel (PAC), derived from Taxus brevifolia, is used to treat solid tumours but causes reproductive toxicity due to oxidative stress, affecting sperm quality and testicular tissue. Nerolidol (NRL), an antioxidant sesquiterpene alcohol, has not been studied for its potential to reduce PAC-induced reproductive damage. This study investigates NRL's ability to mitigate PAC-induced reproductive toxicity in rats. Forty healthy adult male Spraque Dawley rats were randomly divided into four equal groups (Control, PAC, NRL, PAC + NRL). PAC was given intraperitoneally at a dose of 2 mg/kg once a week for 4 weeks. NRL was given orally at a dose of 100 mg/kg/day for 4 weeks. Control group received PAC and NRL vehicles. After 4 weeks, testis tissue samples were collected, and parameters, including oxidants, antioxidants, sperm motility, density, abnormal spermatozoon ratios and cytokines, were measured. PAC administration increased oxidant levels and decreased antioxidant enzyme activities. Nerolidol mitigated these alterations significantly. Similarly, PAC elevated IL-1, IL-6, TNF-alpha levels and lowered IL-10 levels, these effects attenuated by nerolidol in the PAC + NRL group. In conclusion, it was determined that PAC induces reproductive toxicity through oxidative stress, and NRL demonstrates potential in ameliorating these effects through its antioxidant activity.
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    SYNTHESIS OF NEW 6-[4-(2-FLUOROPHENYLPIPERAZINE-1-YL)]-3(2H)-PYRIDAZINONE-2-ACETHYL-2-(SUBSTITUTEDBENZAL)HYDRAZONE DERIVATIVES AND EVULATION OF THEIR CYTOTOXIC EFFECTS IN LIVER AND COLON CANCER CELL LINES
    (Springer, 2019) Ozdemir, Zeynep; Basak-Turkmen, Nese; Ayhan, Idris; Ciftci, Osman; Uysal, Mehtap
    In this study, seven new 3(2H)-pyridazinone derivatives expected to show cytotoxic activity in liver and colon cancer cell lines were synthesized. Their structures were confirmed by the IR, H-1-NMR, C-13-NMR spectra and elementary analyses. Compunds V-1-V-7 were tested on HEP3B (liver cancer) and HTC116 (colon cancer) cell lines for cytotoxicity by using MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] proliferation assay. Human fibroblast cells were used as safety control in these tests. 6-[4-(2-Fluorophenyl)piperazine-1-yl]-3(2H)-pyridazinone-2-acetyl-2-(2-chlorobenzal) hydrazone (compound V-3) was the most active agent with respect to HEP3B and HTC116 cell lines.