Klinik Öncesi Bilimleri Bölümü Makale Koleksiyonuhttps://hdl.handle.net/20.500.12418/2482024-03-28T20:20:28Z2024-03-28T20:20:28ZThe Effects of Sunitinib in Healthy and Cisplatin-Induced RatsDemirtaş, LeventGürbüzel, MehmetAkbaş, Emin MuratTahirler, HilalKarataş, ÖzhanArslan, Yusuf Kemalhttps://hdl.handle.net/20.500.12418/148112024-03-07T21:47:29Z0004-01-01T00:00:00ZThe Effects of Sunitinib in Healthy and Cisplatin-Induced Rats
Demirtaş, Levent; Gürbüzel, Mehmet; Akbaş, Emin Murat; Tahirler, Hilal; Karataş, Özhan; Arslan, Yusuf Kemal
Sunitinib is a multitargeted kinase inhibitor that inhibits many receptor tyrosine kinases and has been used in the treatment of gastrointestinal stromal tumors, metastatic renal cell carcinoma, and pancreatic neuroendocrine tumors. In this study, the effects of sunitinib given to rats, both alone and after stress with cisplatin, were investigated. The animals were divided into four groups – (1) control group (C) administered interperitoneally with a single dose 0.9% saline, (2) Cis group administered a single dose (7 mg/kg) of cisplatin, (3) Sun group administered 10 mg/kg sunitinib for seven days, and (4) Cis+Sun group administered 10 mg/kg sunitinib for seven days after a single dose (7 mg/kg) of cisplatin. After these applications, the rats were sacrificed, and blood and tissue samples were taken for biochemical and histopathological evaluations. Sunitinib did not show any effect on urea, creatine, and kidney IL1β and TGF-β3 expression levels when administered alone; it increased ALT, AST, and IL-38 levels. When sunitinib was given to the cisplatin-induced rats, it was observed that the increase in ALT, AST, and IL-38 levels increased more than the rats that was given only sunitinib. According to the data obtained, sunitinib does not cause a significant change in kidney tissue under both normal and stress conditions, while it creates stress in liver tissue. In addition, its toxicity in the liver becomes more certain as a result of its combination with cisplatin.
0004-01-01T00:00:00ZMechanism of anticancer effect of gambogic acid on gastric signet ring cell carcinomaJoha, ZiadÖztürk AyşegülYulak FatihKarataş, ÖzhanAtaseven Hilmihttps://hdl.handle.net/20.500.12418/148102024-03-07T21:47:27Z0016-01-01T00:00:00ZMechanism of anticancer effect of gambogic acid on gastric signet ring cell carcinoma
Joha, Ziad; Öztürk Ayşegül; Yulak Fatih; Karataş, Özhan; Ataseven Hilmi
Gambogic acid has demonstrated inhibitory effects on the growth of various cancer cell types, such as breast cancer, pancreatic cancer, prostate cancer, lung cancer, and osteosarcoma. This study aims to investigate the antiproliferative activity of Gambogic acid on SNU-16 cells derived from gastric signet ring cell carcinoma and elucidate the underlying mechanisms. The cytotoxic effect of gambogic acid was evaluated in SNU-16 cells by treating them with different concentrations of the compound, and the XTT cell viability assay was employed to assess cell viability. ELISA was used to measure bax, BCL- 2, caspase 3, PARP, and 8-oxo-dG levels. Additionally, immunofluorescence staining was applied to assess 8-oxo-dG and LC3β levels in SNU-16 cells. It was observed that gambogic acid exerted a dose-dependent and statistically significant antiproliferative effect on SNU-16 cells. The IC50 value of gambogic acid in SNU-16 cells was found to be 655.1 nM for 24 h. Subsequent investigations conducted using the IC50 dose revealed a significant upregulation of apoptotic proteins including cleaved caspase 3, Bax, and cleaved PARP (p < 0.001), along with a downregulation of BCL-2 (p < 0.001), an anti-apoptotic protein. Moreover, the administration of this drug led to an upregulation of 8-oxo-dG (p < 0.001), a widely acknowledged biomarker indicating oxidative damage in DNA, as well as an increase in LC3β levels (p < 0.05), a marker associated with autophagy. The antiproliferative effect of gambogic acid against gastric signet ring cell carcinoma is attributed to its ability to induce apoptosis and autophagy. This discovery highlights the promising potential of gambogic acid as a treatment option for gastric signet ring cell carcinoma.
0016-01-01T00:00:00ZProtective effect of Allium scorodoprasum L. ethanolic extract in cyclophosphamide-induced hepatotoxicity model in ratsGüngör, HüseyinEkici, MehmetKarataş, ÖzhanDik, Burakhttps://hdl.handle.net/20.500.12418/148092024-03-07T21:47:27Z0020-01-01T00:00:00ZProtective effect of Allium scorodoprasum L. ethanolic extract in cyclophosphamide-induced hepatotoxicity model in rats
Güngör, Hüseyin; Ekici, Mehmet; Karataş, Özhan; Dik, Burak
Objectives Cyclophosphamide is a chemotherapeutic agent and immunosuppressant drug; however, it damages the liver. This study investigates the protective effect of ethanolic extract of Allium scorodoprasum (ASE) on cyclophosphamide-induced liver injury.
Methods Twenty-eight Wistar albino rats were randomly divided into four groups (n = 7 per group): healthy rats, cyclophosphamide (200 mg/kg), cyclophosphamide (200 mg/kg) + ASE (100 mg/kg) and cyclophosphamide (200 mg/kg) + ASE (200 mg/kg). ASE was administered for 14 days, and the rats were euthanized 24 h after cyclophosphamide administration.
Key findings Cyclophosphamide treatment leads to an increase in serum levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, total cholesterol, triglycerides, low-density lipoprotein and very low-density lipoprotein, as well as an increase in the liver levels of malondialdehyde, tumour necrosis factor, interleukin (IL)-1β and IL-6, while high-density lipoprotein levels decrease. Treatment with cyclophosphamide caused liver necrosis and postnecrotic cell infiltration; however, pathological changes were prevented by ASE. 8-Hydroxy-2ʹ- deoxyguanosine, anti-4-hydroxynenal antibody and anti-dityrosine levels increased in rats treated with cyclophosphamide and decreased in the groups treated with ASE. These changes were dose dependent in the ASE-treated groups.
Conclusions Treatment with cyclophosphamide caused liver damage due to oxidative stress and inflammation. ASE regulated the damage at high doses because it has potent antioxidant and anti-inflammatory ingredients. In future studies, it may be beneficial to administer ASE in higher doses or for longer periods of time.
0020-01-01T00:00:00ZThe effects of sorafenib in healthy and cisplatin-treated ratsDemirtaş, LeventGürbüzel, MehmetTahirler, HilalAkbaş, Emin MuratKarataş, ÖzhanArslan, Yusuf Kemalhttps://hdl.handle.net/20.500.12418/148082024-03-07T21:47:29Z0007-01-01T00:00:00ZThe effects of sorafenib in healthy and cisplatin-treated rats
Demirtaş, Levent; Gürbüzel, Mehmet; Tahirler, Hilal; Akbaş, Emin Murat; Karataş, Özhan; Arslan, Yusuf Kemal
Background. Sorafenib is a multikinase inhibitor currently used in the treatment of hepatocellular carcinoma, renal cell carcinoma and thyroid cancer.
Objectives. The literature on this agent is scarce. This study aimed to evaluate the effects of sorafenib when administered to both healthy and cisplatin-induced rats.
Materials and methods. The animals were divided into 4 groups: 1) control group that received 0.9% saline intraperitoneally (C); 2) group administered a single dose (7 mg/kg) of cisplatin (Cis); 3) a group administered 20 mg/kg of sorafenib for 7 days (Sor); 4) group administered 20 mg/kg of sorafenib followed by 7 mg/kg of cisplatin for 7 days (Cis+Sor). All animals were sacrificed 7 days after the completion of their treatment arm, and serum and tissue samples were taken.
Results. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and interleukin 38 (IL-38) levels were increased in the Sor and Cis+Sor groups compared to the control group. When compared with the control group, serum urea, creatinine, kidney IL-1β, and tumor necrosis factor alpha (TNF-α) levels did not change in the Sor group. When compared to the Cis group, the levels of these parameters decreased in the Cis+Sor group.
Conclusions. According to the data obtained, sorafenib caused liver toxicity when given to both healthy and cisplatin-induced rats. While sorafenib did not cause any significant changes in the kidneys when given to healthy rats, it had a healing effect in kidneys after stress induced by cisplatin.
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