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    Arbutin abrogates cisplatin-induced hepatotoxicity via upregulating Nrf2/HO-1 and suppressing genotoxicity, NF-?B/iNOS/TNF-? and caspase-3/Bax/Bcl2 signaling pathways in rats
    (Oxford Univ Press, 2024) Okkay, Irmak Ferah; Famurewa, Ademola; Bayram, Cemil; Okkay, Ufuk; Mendil, Ali Sefa; Sezen, Selma; Ayaz, Teslime
    Background: Cisplatin is a potent anticancer agent widely employed in chemotherapy. However, cisplatin leads to toxicity on non-targeted healthy organs, including the liver. We investigated the hepatoprotective mechanism of arbutin (ARB), a glycosylated hydroquinone, against cisplatin-induced hepatotoxicity. Methods: Rats were orally administered with ARB (ARB1 = 50 mg/kg; ARB2 = 100 mg/kg) for 14 consecutive days against hepatotoxicity induced by a single dose of cisplatin (10 mg/kg) on day 15. Three days after the intraperitoneal cisplatin injection, serum and liver tissue were collected for subsequent analyses. Results: Cisplatin triggered marked increases in serum AST, ALT, and ALP activities, hepatic malondialdehyde (MDA) and reactive oxygen species (ROS) coupled with a considerable diminution in hepatic activities of superoxide dismutase (SOD), catalase (CAT) and the concentration of reduced glutathione (GSH). The gene expressions of interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF-alpha), and IL-6 were notably increased. The pre-administration of ARB1 and ARB2 reduced AST, ALT and ALP in serum and restored SOD, CAT, GSH, ROS, MDA and cytokine levels which was also evidenced by alleviated hepatic lesions. Further, cisplatin-induced prominent alterations in the gene expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), iNOS, NF-kappa B, Bax, Bcl-2, caspase-3 and 8-OHdG in the liver. Interestingly, ARB protected the liver and mitigated the cisplatin-induced alterations in serum AST, ALT, ALP, and reduced hepatic redox markers, 8-OdG, inflammatory markers and gene expressions. Conclusion: The findings demonstrate that ARB is a potential protective adjuvant against cisplatin-induced hepatotoxicity via inhibition of hepatic oxidative stress, inflammation, and apoptosis.
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    Assessment of antimicrobial activity and In Vitro wound healing potential of ZnO nanoparticles synthesized with Capparis spinosa extract
    (Ekim 2023) Sezen, Selma; Ertuğrul, Muhammed Sait; Balpınar, Özge; Bayram, Cemil; Özkaraca, Mustafa; Okkay, Irmak Ferah; Hacımüftüoğlu, Ahmet; Güllüce, Medine
    Agents that will accelerate wound healing maintain their clinical importance in all aspects. The aim of this study is to deter mine the antimicrobial activity of zinc oxide nanoparticles (ZnO NPs) ZnO nanoparticles obtained by green synthesis from Capparis spinosa L. extract and their efect on in vitro wound healing. ZnO NPs were synthesized and characterized using Capparis spinosa L. extract. ZnO NPs were tested against nine ATCC-coded pathogen strains to determine antimicrobial activity. The efects of diferent doses (0.0390625–20 µg/mL) of NPs on cell viability were determined by MTT assay. The efect of ZnO NPs doses (0.0390625 µg/mL, 0.078125 µg/mL, 0.15625 µg/mL, 0.3125 µg/mL, 0.625 µg/mL, 1.25 µg/mL) that increase proliferation and migration on wound healing was investigated in an in vitro wound experiment. Cell culture medium obtained from the in vitro wound assay was used for biochemical analysis, and plate alcohol-fxed cells were used for immunohistochemical staining. It was determined that NPs formed an inhibition zone against the tested Gram-positive bacteria. The ZnO NPs doses determined in the MTT test provided faster wound closure in in-vitro conditions compared to the DMSO group. Biochemical analyses showed that infammation and oxidative status decreased, while antioxidant levels increased in ZnO NPs groups. Immunohistochemical analyses showed increased expression levels of Bek/FGFR2, IGF, and TGF-β associated with wound healing. The fndings reveal the antimicrobial efect of ZnO nanoparticles obtained using Capparis spinosa L. extract in vitro and their potential applications in wound healing.
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    Assessment of antimicrobial activity and In Vitro wound healing potential of ZnO nanoparticles synthesized with Capparis spinosa extract
    (Springer Heidelberg, 2023) Sezen, Selma; Ertugrul, Muhammed Sait; Balpinar, Ozge; Bayram, Cemil; Ozkaraca, Mustafa; Okkay, Irmak Ferah; Hacimuftuoglu, Ahmet
    Agents that will accelerate wound healing maintain their clinical importance in all aspects. The aim of this study is to determine the antimicrobial activity of zinc oxide nanoparticles (ZnO NPs) ZnO nanoparticles obtained by green synthesis from Capparis spinosa L. extract and their effect on in vitro wound healing. ZnO NPs were synthesized and characterized using Capparis spinosa L. extract. ZnO NPs were tested against nine ATCC-coded pathogen strains to determine antimicrobial activity. The effects of different doses (0.0390625-20 mu g/mL) of NPs on cell viability were determined by MTT assay. The effect of ZnO NPs doses (0.0390625 mu g/mL, 0.078125 mu g/mL, 0.15625 mu g/mL, 0.3125 mu g/mL, 0.625 mu g/mL, 1.25 mu g/mL) that increase proliferation and migration on wound healing was investigated in an in vitro wound experiment. Cell culture medium obtained from the in vitro wound assay was used for biochemical analysis, and plate alcohol-fixed cells were used for immunohistochemical staining. It was determined that NPs formed an inhibition zone against the tested Gram-positive bacteria. The ZnO NPs doses determined in the MTT test provided faster wound closure in in-vitro conditions compared to the DMSO group. Biochemical analyses showed that inflammation and oxidative status decreased, while antioxidant levels increased in ZnO NPs groups. Immunohistochemical analyses showed increased expression levels of Bek/FGFR2, IGF, and TGF-beta associated with wound healing. The findings reveal the antimicrobial effect of ZnO nanoparticles obtained using Capparis spinosa L. extract in vitro and their potential applications in wound healing.
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    Neuroprotective effect of methanol extract of Capparis spinosa L. fruits in an in-vitro experimental model of Parkinson’s disease
    (MediHealth Academy Yayıncılık, 2022) Sezen, Selma; Yesilyurt, Fatma; Özkaraca, Mustafa; Bayram, Cemil; Alaylar, Burak; Güllüce, Medine; Hacımüftüoğlu, Ahmet
    Aim: Parkinson’s disease (PD) is the second most widespread neurodegenerative disease. This study, it was aimed to investigate the effect of methanol extract obtained from Capparis spinosa L. fruits, which are known to have important bioactive components, on in-vitro experimental PD model. Material and Method: After collecting Capparis spinosa L. fruits from Alanya/Antalya, methanol extract was prepared by drying and grinding. SH-SY5Y cells grown in flasks were transferred to 96 well plates and were incubated until 80% cell density was reached. Different doses of methanol extract were applied to the cells 30 minutes before the PD model was formed. For the PD model, SH-SY5Y cells were exposed to 200 µM 6-OHDA for 24 hours. MTT analysis was performed to assess the viability of SH-SY5Y cells at the end of the 24-hour period. TOS, TAC, and IL-17A levels in the cell medium were determined using the ELISA method. Expression of TNFα and α-synuclein was defined using the immunohistochemical method. Results: Cell viability was found to be higher in all treatment groups than in the 6-OHDA group. Moderate levels of TNFα and α-synuclein positivity were observed in the 1500 µg/ml methanol extract group. It was determined that TOS and TAC levels change depending on the dose. It has been determined that the level of IL-17A decreases at low doses. Statistical significance was found between the groups. Conclusion: When the findings were examined, it was determined that the methanol extract obtained from Capparis spinosa L. fruits reduced oxidative stress and IL-17A levels at low doses and provided a neuroprotective effect by increasing the antioxidant capacity.
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    Parthenolide as a potential analgesic in the treatment of paclitaxel?induced neuropathic pain: the rat modeling
    (Haziran 2023) Toraman, Emine; Bayram, Cemil; Sezen, Selma; Özkaraca, Mustafa; Hacımüftüoğlu, Ahmet; Budak, Harun
    In this study, we determined the therapeutic efect of parthenolide (PTL), the active component of Tanacetum parthenium, on neuropathic pain caused by paclitaxel (PTX), a chemotherapeutic drug frequently used in cancer treatment, at the gene and protein levels. To this end, 6 groups were formed: control, PTX, sham, 1 mg/PTL, 2 mg/kg PTL, and 4 mg/kg PTL. Pain formation was tested by Randall-Selitto analgesiometry and locomotor activity behavioral analysis. Then, PTL treatment was performed for 14 days. After the last dose of PTL was taken, Hcn2, Trpa1, Scn9a, and Kcns1 gene expressions were measured in rat brain (cerebral cortex/CTX) tissues. In addition, changes in the levels of SCN9A and KCNS1 proteins were determined by immunohistochemical analysis. Histopathological hematoxylin-eosin staining was also performed to investigate the efect of PTL in treating tissue damage on neuropathic pain caused by PTX treatment. When the obtained data were analyzed, pain threshold and locomotor activity decreased in PTX and sham groups and increased with PTL treatment. In addition, it was observed that the expression of the Hcn2, Trpa1, and Scn9a genes decreased while the Kcns1 gene expression increased. When protein levels were examined, it was determined that SCN9A protein expression decreased and the KCNS1 protein level increased. It was determined that PTL treatment also improved PTX-induced tissue damage. The results of this study demonstrate that non-opioid PTL is an efective therapeutic agent in the treatment of chemotherapy-induced neuropathic pain, especially when used at a dose of 4 mg/kg acting on sodium and potassium channels
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    Parthenolide as a potential analgesic in the treatment of paclitaxel-induced neuropathic pain: the rat modeling
    (Springer, 2023) Toraman, Emine; Bayram, Cemil; Sezen, Selma; Ozkaraca, Mustafa; Hacimuftuoglu, Ahmet; Budak, Harun
    In this study, we determined the therapeutic effect of parthenolide (PTL), the active component of Tanacetum parthenium, on neuropathic pain caused by paclitaxel (PTX), a chemotherapeutic drug frequently used in cancer treatment, at the gene and protein levels. To this end, 6 groups were formed: control, PTX, sham, 1 mg/PTL, 2 mg/kg PTL, and 4 mg/kg PTL. Pain formation was tested by Randall-Selitto analgesiometry and locomotor activity behavioral analysis. Then, PTL treatment was performed for 14 days. After the last dose of PTL was taken, Hcn2, Trpa1, Scn9a, and Kcns1 gene expressions were measured in rat brain (cerebral cortex/CTX) tissues. In addition, changes in the levels of SCN9A and KCNS1 proteins were determined by immunohistochemical analysis. Histopathological hematoxylin-eosin staining was also performed to investigate the effect of PTL in treating tissue damage on neuropathic pain caused by PTX treatment. When the obtained data were analyzed, pain threshold and locomotor activity decreased in PTX and sham groups and increased with PTL treatment. In addition, it was observed that the expression of the Hcn2, Trpa1, and Scn9a genes decreased while the Kcns1 gene expression increased. When protein levels were examined, it was determined that SCN9A protein expression decreased and the KCNS1 protein level increased. It was determined that PTL treatment also improved PTX-induced tissue damage. The results of this study demonstrate that non-opioid PTL is an effective therapeutic agent in the treatment of chemotherapy-induced neuropathic pain, especially when used at a dose of 4 mg/kg acting on sodium and potassium channels.
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    The in-vitro Wound Healing Potential of Essential Oil Extracted from Mentha longifolia L.
    (Marmara Univ, 2023) Sezen, Selma; Ertugrul, Muhammed Sait; Bayram, Cemil; Ozkaraca, Mustafa; Koc, Taha Yasin; Demir, Abdussamed Yasin; Gulluce, Medine
    Products from Mentha species are widely used in medical applications, including wound healing, due to the bioactive compounds they may contain. However, data on the effect of Mentha longifolia L. on wound healing are limited. This study investigated the antimicrobial and wound healing-promoting effects of Mentha longifolia L. essential oil using in vitro methods. The chemical compositions of the essential oil were identified using gas chromatography/mass spectrometry, while the agar well diffusion and disk diffusion methods were used to determine antimicrobial activity against pathogenic strains. A scratch wound healing assay was performed following determination of the cytotoxic dose in human fibroblast cell lines. The media were used for biochemical analysis 48 h after the in vitro wound model. Immunohistochemical staining was applied to determine the contribution of the essential oil to wound healing. The essential oil exhibited varying levels of antimicrobial activity against the tested pathogens and increased cell viability. All doses in the scratch wound healing assay promoted wound closure in a shorter time than in the control group. TAC levels were higher in the treated groups than in the control group, while TOS, IL-6, and TNF-alpha levels were lower. Levels of expression of FGF 2, IGF, and TGF-beta were higher in the treated groups than in the control group at increasing doses. The essential oil of Mentha longifolia L. exhibited antimicrobial effects and improved wound healing at doses of 5 mu g/mL and 10 mu g/mL.