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    Cytotoxic effects, microbiological analysis and inhibitory properties on carbonic anhydrase isozyme activities of 2-hydroxy-5-methoxyacetophenone thiosemicarbazone and its Cu(II), Co(II), Zn(II) and Mn(II) complexes
    (Springer, 2021) Ucar, Asuman; Findik, Mukerrem; Kuzu, Muslum; Pehlivanoglu, Suray; Sayin, Ulku; Sayin, Zafer; Akgemci, Emine Guler
    Metal complexes of thiosemicarbazones have been receiving considerable attention in biological applications such as antimicrobial and anticancer therapies. In this work, Co(II), Zn(II) and Mn(II) complexes of 2-hydroxy-5-methoxyacetophenone thiosemicarbazone (HMAT) were synthesized for the first time and characterized by EPR, FT-IR, NMR, UV-Vis spectroscopies, TG/DSC and elemental analysis. X-ray powder diffraction analysis was carried out for Zn(II) complex. HMAT and its Cu(II), Co(II), Zn(II) and Mn(II) complexes were tested as enzyme inhibitory agents. All compounds are effective inhibitor of cytosolic carbonic anhydrase I and II isoforms (hCA I and II) enzymes. IC(50)values of HMAT and its Cu(II), Co(II), Zn(II) and Mn(II) complexes were determined as 93.35, 324.46, 25.67, 1.06 and 22.36 mu M for CA I isozyme and 99.02, 86.64, 57.76, 10.34 and 36.48 mu M for CA II isozyme, respectively. The evaluation of potential cytotoxic effects of the compounds was performed against normal epithelial breast mammary gland CRL-4010, estrogen-positive low metastatic MCF-7 and triple negative highly metastatic MDA-MB-231 breast adenocarcinoma cell lines by MTT assay. The results showed that the tested metal complexes have high cytotoxic effects than their ligand molecule. In particular, the Cu(II) complex displayed preciously high cytotoxic properties different from the others. Given these facts, the Cu(II) complex could be debated as potential chemotherapeutic molecule against drug-resistant breast cancer cells. Minimum inhibitory concentrations of the compounds against the test organisms were also detected for the microbiological analysis.
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    Role of geraniol against lead acetate-mediated hepatic damage and their interaction with liver carboxylesterase activity in rats
    (Taylor & Francis Ltd, 2018) Ozkaya, Ahmet; Sahin, Zafer; Kuzu, Muslum; Saglam, Yavuz Selim; Ozkaraca, Mustafa; Uckun, Mirac; Yologlu, Ertan
    In this study, the effect of geraniol (50 mg/kg for 30 d), a natural antioxidant and repellent/antifeedant monoterpene, in a rat model of lead acetate-induced (500 ppm for 30 d) liver damage was evaluated. Hepatic malondialdehyde increased in the lead acetate group. Reduced glutathione unchanged, but glutathione S-transferase, glutathione reductase, as well as carboxylesterase activities decreased in geraniol, lead acetate and geraniol+lead acetate groups. 8-OhDG immunoreactivity, mononuclear cell infiltrations and hepatic lead concentration were lower in the geraniol+lead acetate group than the lead acetate group. Serum aspartate aminotransferase and alanine aminotransferase activities increased in the Pb acetate group. In conclusion, lead acetate causes oxidative and toxic damage in the liver and this effect can reduce with geraniol treatment. However, we first observed that lead acetate, as well as geraniol, can affect liver carboxylesterase activity.
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    Safranal's therapeutic effects in rat models of polycystic ovary syndrome
    (Springernature, 2023) Cellat, Mustafa; Kuzu, Muslum; Guvenc, Mehmet; Yuksel, Murat; Kanat, Ozgur; Bozkurt, Yesim Akaydin; Etyemez, Muhammed
    Polycystic ovary syndrome is one of the leading causes of female infertility in reproductive age. In this work, the protective effects of safranal against letrozole-induced polycystic ovary syndrome in rats were examined. For this purpose, 32 Wistar albino female rats were split into four groups. Each group received the following treatments for 21 days: Group 1 received carboxymethylcellulose (1%, 2 ml/kg); Group 2, letrozole (1 mg/kg), Group 3, safranal (200 mg/kg); and Group 4 letrozole and safranal via oral gavage. We identified estrus cycles in the rats and analyzed various parameters in their serum and ovarian tissues, as well as histopathologic findings. The parameters studied included C-reactive protein, glucose, total cholesterol, triacylglyceride, high-density lipoprotein, low-density lipoprotein, follicle-stimulating hormone, estradiol, and luteinizing hormone levels in serum. Additionally, the study measured malondialdehyde, glutathione, glutathione peroxidase, and catalase levels in ovarian tissue. We also examined tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta parameters in serum and ovarian tissues, as well as nuclear factor erythroid 2-related factor-2 and heme oxygenase-1 protein levels. In the letrozole group, the estrus cycle was disrupted, and all parameters, except for glutathione and glutathione peroxidase, showed impairments compared to the control group. The findings showed that glucose, triacylglyceride, catalase, and heme oxygenase-1 levels slightly improved after safranal treatment, however, other parameters showed statistically significant improvements. Furthermore, safranal treatment reduced the development of cystic follicles while preserving tissue architecture, as revealed by histopathologic findings. Based on the results obtained, it may be argued that safranal's antioxidant and anti-inflammatory properties, along with its ability to regulate sex hormone levels and manage dyslipidemia, make it a promising solution for patients with polycystic ovary syndrome.