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    An Experimental Insight Into the Role of Agomelatine in Renal Ischemia/Reperfusion Injury
    (Wiley, 2024) Aykora, Damla; Bahar, Mehmet Refik; Tanbek, Kevser; Ozturk, Dilara Altay; Karaca, Elif; Sandal, Suleyman; Tekin, Suat
    Acute kidney injury (AKI) is one of the leading causes of chronic kidney disease and accounts for 50%-75% of mortality following renal pathologies or organ transplantation. Ischemia-reperfusion injury (IRI) involves an interrupted blood supply to organs and the kidney; IRI exacerbates AKI development. Owing to several pharmacological treatment methods, AKI still has a poor prognosis, and novel therapeutic options are needed. Agomelatine (AGM) is a melatonin receptor agonist (MT1 and MT2) with increased bioavailability and lipophilicity. In this study, we aimed to investigate the antioxidant and anti-inflammatory effects of AGM in experimental renal IRI via long-term and short-term applications. Sixty male Sprague-Dawley rats were randomly divided into six groups (n = 10): the control, I/R, AGM20S, AGM40S, AGM20L, and AGM40L groups. Following the establishment of the renal IRI model, the rats received agomelatine at 20 and 40 mg/kg orally, and agomelatine solvent (hydroxyethylcellulose) was used as a vehicle. At the end of the experiment, blood samples and renal tissues were harvested for histopathological and biochemical analysis. Urea, creatinine, tumor necrosis factor (TNF-alpha), and interleukin-1 beta (IL-1 beta) levels were measured in blood serum samples. Malondialdehyde (MDA) levels and increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), and total glutathione (GSH) levels were measured in renal tissue supernatants. Our biochemical results indicated that AGM reduced creatinine, TNF-alpha, IL-1 beta, and malondialdehyde levels and increased SOD, CAT, GSHPx, and total GSH levels. Agolematine reduced infiltration, intratubular hemorrhage, and intratubular cast formation histopathologically. Our results suggest that AGM could be a potential therapeutic adjuvant agent for ischemia-reperfusion injury in the kidney and several other organs.
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    Effects of intracerebroventricular MOTS-c infusion on thyroid hormones and uncoupling proteins
    (Springer Heidelberg, 2023) Bahar, Mehmet Refik; Tekin, Suat; Beytur, Asiye; Onalan, Ebru Etem; Ozyalin, Fatma; Colak, Cemil; Sandal, Suleyman
    This study was conducted to determine the possible effects of intracerebroventricular MOTS-c infusion on thyroid hormones and uncoupling proteins (UCPs) in rats. Forty male Wistar Albino rats were divided into 4 groups with 10 animals in each group: control, sham, 10 and 100 mu M MOTS-c. Hypothalamus, blood, muscle, adipose tissues samples were collected for thyrotropin-releasing hormone (TRH), UCP1 and UCP3 levels were determined by the RT-PCR and western blot analysis. Serum thyroid hormone levels were determined by the ELISA assays. MOTS-c infusion was found to increase food consumption but it did not cause any changes in the body weight. MOTS-c decreased serum TSH, T3, and T4 hormone levels. On the other hand, it was also found that MOTS-c administration increased UCP1 and UCP3 levels in peripheral tissues. The findings obtained in the study show that central MOTS-c infusion is a directly effective agent in energy metabolism.
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    Investigation of the protective effect of Lavandula stoechas against the damage caused by Bisphenol A in the liver tissue of rats
    (Cell Press, 2024) Aydin, Merve; Kose, Evren; Karaca, Elif Taslidere; Tanbek, Kevser; Sandal, Suleyman
    The present study aims to explore the hepatoprotective potential of Lavandula stoechas (LS) against Bisphenol A (BPA)-induced liver toxicity. In this experiment, 32 male rats were utilized and categorized into control, LS, BPA, and BPA + LS groups for the study. Each group received 50 mg/kg of the respective substance. Throughout the 28-day experiment, the control group did not receive any applications. The LS oil was administered intraperitoneally, while BPA was given through oral gavage. At the end of the experiment, rats were anesthetized, and blood was taken from the heart. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) values were measured from serum samples. Malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) measurements were performed in liver tissue. The histological structure was observed using hematoxylin and eosin staining methods. The BPA group showed higher AST levels compared to the control group, but the BPA + LS group exhibited a significant decrease in AST levels compared to the BPA group. Additionally, TB levels were lower in the BPA + LS group compared to the BPA group. MDA levels increased in BPA-treated groups compared to others. The LS-treated groups showed higher SOD levels compared to the control group. Furthermore, an evident increase was noted in the BPA + LS group in comparison to the BPA group. The BPA group exhibited a significant rise in OSI value compared to the control. It was concluded that LS has a protective impact against BPA-induced liver toxicity. The LS-treated groups showed higher SOD levels compared to the control group. Furthermore, a significant increase was noted in the BPA + LS group in comparison to the BPA group. The BPA group exhibited a significant rise in OSI value compared to the control. It was concluded that LS has a protective impact against BPAinduced liver toxicity.
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    Silyl-functionalised silver rhodium and iridium N-heterocyclic carbene complexes with promising cytotoxicity and antimicrobial potential
    (Elsevier, 2022) Karatas, Mert Olgun; Keskin, Tuba; Ozdemir, Namik; Kucukbay, Hasan; Tekin, Suat; Mansur, Ahmet; Sandal, Suleyman
    In the present study, we have synthesized Ag, Rh, and Ir complexes of a silyl-substituted NHC ligand in order to investigate their biological properties. Firstly, Ag-NHC (2) complex was synthesized by the interaction of Ag2O with benzimidazolium iodide (1). Rh-(3) and Ir-NHC (4) complexes were synthesized by the transmetalation reaction between Ag-NHC and [M(cod)Cl]2 (M = Rh or Ir) dimers. The complexes were characterised by NMR spectroscopy and elemental analyses, and crystal structures of Rh-and Ir-NHC (3 and 4) were also reported. The cytotoxic effects of the complexes were tested on four human cancer cell lines and the antimicrobial activities of the complexes were tested against a panel of nine pathogenic microorganisms. The complexes performed com-parable or better activity than standards, cisplatin and AgNO3.
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    Synthesis of New Cinnamoyl-Amino Acid Conjugates and in Vitro Cytotoxicity and Genotoxicity Studies
    (Wiley-V C H Verlag Gmbh, 2022) Caliskan, Eray; Ozturk, Dilara Altay; Koran, Kenan; Tekin, Suat; Sandal, Suleyman; Erkan, Sultan; Gorgulu, Ahmet Orhan
    Amino acid conjugates are described by the reaction of amino acids with bioactive organic groups such as vitamins, hormones, flavonoids, steroids, and sugars. In this study, 12 new conjugates were synthesized by reaction of cinnamic acid derivatives with various amino acids. Cytotoxic studies against four different human cancer cells (MCF7, PC-3, Caco-2, and A2780) were carried out by MTT assay method at five different concentrations. The structure-activity relationships based on the cell viability rates were evaluated. To compare the anticancer activities of the compounds using computational chemistry methods, they were docked against A2780 human ovarian cancer, Michigan Cancer Foundation-7 (MCF7), human prostate cancer (PC-3) and human colon epidermal adenocarcinoma (Caco-2) cell lines and compared with the standard 5-Fluorouracil. The results indicate that the efficacy of cinnamic acid derivatives increases with the presence of amino acids. Comet assay was conducted to understand whether the cell deaths occur through DNA damage mechanism and the results exhibit that the changes in the specified parameters were statistically significant (p<0.05). Our study demonstrated that the compounds cause cell death through the formation of DNA damage mechanism.
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    The first peptide derivatives of dioxybiphenyl-bridged spiro cyclotriphosphazenes: In vitro cytotoxicity activities and DNA damage studies
    (Academic Press Inc Elsevier Science, 2023) Koran, Kenan; Caliskan, Eray; Ozturk, Dilara Altay; Capan, Irfan; Tekin, Suat; Sandal, Suleyman; Gorgulu, Ahmet Orhan
    In this study, we aimed to synthesize new peptide-substituted cyclotriphosphazenes from a series of tyrosine -based peptides and dioxyphenyl-substituted spirocyclotriphosphazenes, and to evaluate their in vitro cytotox-icity and genotoxicity activities. Genotoxicity studies were conducted to understand whether the cytotoxic compounds cause cell death through DNA damage. The structures of the novel series of phosphazenes were characterized by FT-IR, elemental analysis, MS, 1D (31P, 1H, and 13C-APT NMR), and 2D (HETCOR) NMR spectroscopic techniques. In vitro cytotoxic activities were carried out against human breast (MCF-7), ovarian (A2780), prostate (PC-3), colon (Caco-2) cancer cell lines and human normal epithelial cell line (MCF-10A) at different concentrations by using an MTT assay. The compounds showed considerable reductions in cell viability against all human cancer cell lines. Especially, the compounds exhibited notable effects in A2780 cell lines (p < 0.05). The IC50 values of the compounds in the A2780 cell line were calculated to be 1.914 mu M for TG, 20.21 mu M for TV, 20.45 mu M for TA, 4.643 mu M for TP, 5.615 mu M for BTG, 1.047 mu M for BTV, 27.02 mu M for BTA, 0.7734 mu M for BTP, 21.5 mu M for DTG, 1.65 mu M for DTV, 2.89 mu M for DTA and 4.599 mu M for DTP. DNA damage studies of the compounds were conducted by the comet assay method using tail length, tail density, olive tail moment, head length, and head density parameters, and the results showed that the cell death occurred through DNA damage mechanism. In a nutshell, these compounds show promising cytotoxic effects and can be considered powerful candidate molecules for pharmaceutical applications.