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    Hepato-preventive and anti-apoptotic role of boric acid against liver injury induced by cyclophosphamide
    (Elsevier Gmbh, 2019) Cengiz, Mustafa; Yildiz, Songul Cetik; Demir, Cemil; Sahin, Ilknur Kulcanay; Teksoy, Ozgun; Ayhanci, Adnan
    This study aims to examine cyclophosphamide (CP) exsposure associated toxicity on rat livers and the likely defensive effects of boric acid (BA). The rats used in this study were divided into four groups: control group, CP group, BA group, and BA + CP group. The present study was carried out using routine histological H&E stain, immunohistochemical stain caspase-3 as apoptotic marker, serum biochemical analysis for liver function markers (alanine transaminase (ALT), aspartate transaminase (AST) and alkalen phosphatase (ALP)), oxidative stress markers (total oxidant status (TOS), oxidative stress index (OSI) and total antioxidant capacity marker (TAC)). In the CP group, the levels of ALT, AST, ALP, TOS, OSI and caspase-3 increased whereas TAC levels decreased compared with the control group. In the BA + CP group, the levels of ALT, AST, ALP, TOS, OSI and caspase-3 decreased whereas TAC levels increased compared with the CP group. The histopathological evaluation of light microscope images and immunohistochemical caspase-3 activity in the BA + CP group were found to be decrease compared with those in the CP group. In conclusion, BA was successful in defending the liver against apoptosis and histopathological changes that are attributable to CP.
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    Immunotherapeutic and Cell-Protective Effects of Probiotic Kefir on Cyclophosphamide induced Nephrotoxicity and Urotoxicity in Rats
    (2024) Yıldız, Songül Çetik; Demir, Cemil; Cengiz, Mustafa; Irmak, Halit; Cengiz, Betül Peker; Ayhanci, Adnan
    To evaluate kefir, a naturally occurring fermented dairy product, with pharmacological and therapeutic qualities including antioxidant, anti-apoptotic, and anti-inflammatory effects against cyclophosphamide (CP)-induced hemorrhagic cystitis and nephrotoxicity in rats. For this purpose, experimental rats were divided into 6 groups; control (Group 1), 150 mg/kg CP (Group 2), 5 mg/kg kefir (Group 3), l0 mg/kg kefir (Group 4), 5 mg/kg kefir+150 CP (Group 5), l0 mg/kg kefir+150 CP (Group 6). Since there was no difference in kefirs fermented on different days, kefirs from the 1st, 2nd, and 3rd days were mixed and given to the rats for 12 days, while CP was given as an only dose and i.p. on the 12th day of the experiment. Histologic evaluations revealed that CP caused toxicity in kidney and bladder. On the other hand, biochemical evaluations showed a significant increase in serum blood urea nitrogen (BUN) and creatinine (Cre) levels, which are tissue toxicity markers, and a significant decrease in catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, which are intracellular antioxidant system markers, in the CP-treated experimental group. However, all values were reversed as a result of kefir (5 and 10 mg/kg) treatment. These results showed that kefir is an effective protective agent against CP-induced hemorrhagic cystitis and nephrotoxicity.
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    In Vitro Antitumor and Antioxidant Capacity as well as Ameliorative Effects of Fermented Kefir on Cyclophosphamide-Induced Toxicity on Cardiac and Hepatic Tissues in Rats
    (Mdpi, 2024) Yildiz, Songul Cetik; Demir, Cemil; Cengiz, Mustafa; Irmak, Halit; Cengiz, Betul Peker; Ayhanci, Adnan
    Fermented prebiotic and probiotic products with kefir are very important to slow down and prevent the growth of tumors and to treat cancer by stimulating the immune response against tumor cells. Cyclophosphamide (CPx) is widely preferred in cancer treatment but its effectiveness in high doses is restricted because of its side effects. The aim of this study was to investigate the protective effects of kefir against CPx-induced heart and liver toxicity. In an experiment, 42 Wistar albino rats were divided into six treatment groups: the control (Group 1), the group receiving 150 mg/kg CPx (Group 2), the groups receiving 5 and 10 mg/kg kefir (Groups 3 and 4) and the groups receiving 5 and 10 mg/kg kefir + CPx (Group 5 and 6). Fermented kefirs obtained on different days by traditional methods were mixed and given by gavage for 12 days, while a single dose of CPx was administered intraperitoneally (i.p.) on the 12th day of the experiment. It was observed that alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine kinase-MB (CK-MB), ischemia modified albumin (IMA) and Troponin I values, which indicate oxidative stress, increased in the CPx-administered group, and this level approached that of the control in the CPx + kefir groups. Likewise, as a result of the kefir, the rats' CPx-induced histopathological symptoms were reduced, and their heart and liver tissue were significantly improved. In conclusion, it was observed that kefir had a cytoprotective effect against CPx-induced oxidative stress, hepatotoxicity and cardiotoxicity, bringing their biochemical parameters closer to those of the control by suppressing oxidative stress and reducing tissue damage.
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    Protective properties of kefir on burn wounds of mice that were infected with S. aureus, P. auroginasa and E. coli
    (C M B Assoc, 2019) Yildiz, Songul Cetik; Demir, Cemil; Cengiz, Mustafa; Ayhanci, Adnan
    Burns and burn wounds are very sensitive to infections and cause a large amount of death worldwide. Although burn wound is sterile at the beginning, because of the risk factors such as prolonged hospital stay, immune suppression and burn affecting large surface area, colonisation with Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli occur. For the burn therapy, one of the most important ways is to control bacterial infections. A probiotic fermented milk product kefir has antioxidant, antimicrobial, antiinflammatory, anticancer and various health promoting features. This study aims to examine possible protective properties of kefir which was used on the burn wounds that were infected with S. aureus, P. auroginasa and E. coli. Swiss albino / Balb-c mice were seperated into four groups: (1) used as control group, (2) second-degree burn model+ burn wounds were infected with P.aeruginosa + S.aureus + E.coli, (3) second-burn wounds were treated with sterile pads dressed with kefir and (4) second-degree burn+burn wounds were infected with P. aeruginosa + S.aureus +E.coli before being treated with sterile pads dressed with kefir. The serum biochemical results verified the histopathological results and our findings showed that kefir is an effective product with cell-protecting properties.
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    The protection afforded by kefir against cyclophosphamide induced testicular toxicity in rats by oxidant antioxidant and histopathological evaluations
    (Nature Portfolio, 2024) Yildiz, Songul Cetik; Demir, Cemil; Cengiz, Mustafa; Irmak, Halit; Cengiz, Betul Peker; Ayhanci, Adnan
    Cyclophosphamide (CTX) is the most commonly used effective alkylating drug in cancer treatment, but its use is restricted because its toxic side effect causes testicular toxicity. CTX disrupts the tissue redox and antioxidant balance and the resulting tissue damage causes oxidative stress. In our study based on this problem, kefir against CTX-induced oxidative stress and testicular toxicity were investigated. Rats were divided into 6 groups: control, 150 mg/kg CTX, 5 and 10 mg/kg kefir, 5 and 10 mg/kg kefir + 150 CTX. While the fermented kefirs were mixed and given to the rats for 12 days, CTX was given as a single dose on the 12th day of the experiment. Testis was scored according to spermatid density, giant cell formation, cells shed into tubules, maturation disorder, and atrophy. According to our biochemical findings, the high levels of total oxidant status (TOS), and the low levels of total antioxidant status (TAS) in the CTX group, which are oxidative stress markers, indicate the toxic effect of CTX, while the decrease in TOS levels and the increase in TAS levels in the kefir groups indicate the protective effect of kefir. In the CTX-administered group, tubules with impaired maturation and no spermatids were observed in the transverse section of the testicle, while in the kefir groups, the presence of near-normal tubule structures and tubule lumens despite CTX showed the protective effect of kefir. In our study, it was observed that kefir had a protective and curative effect on CTX-induced toxicity and oxidative stress and could be a strong protector.