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    Cyclophosphamide induced oxidative stress, lipid per oxidation, apoptosis and histopathological changes in rats: Protective role of boron
    (Elsevier Gmbh, 2020) Cengiz, Mustafa; Sahinturk, Varol; Yildiz, Songul Cetik; Sahin, Ilknur Kulcanay; Bilici, Namik; Yaman, Suzan Onur; Altuner, Yilmaz
    Background: Cyclophosphamide (CP) is an alkylating chemotherapeutic drug used in the treatment of many types of cancer. However, as with other chemotherapeutic drugs, the use of CP is limited by the damage to healthy tissues such as testes, bladder and liver as well as cancerous tissue. Boron (B) is a trace element with many biological properties such as antioxidant, anti-apoptotic and anti-lipid per oxidation. Methods: This current study aims to determine protective effects of B on CP induced testicular toxicity. The rats were divided into 4 groups (control, CP, B and B plus CP groups). The testes of experimental animals were taken for histological, apoptotic markers and biochemical analysis. Results: The damage to some seminifer tubules, loss of typical appearance, thinning of seminifer epithelium and relative enlargement of the tubule lumen were watched in testis of the group that administrated CP. Moreover, Bcl-2, TAC and GSH levels decreased while TOC, OSI, MDA, Bax and Caspase-3 levels increased. On the other hand, pretreatment limited to B in the B plus CP group, testicular tissue improved. In addition, Bcl-2, GSH, TAC levels increased, Bax, MDA, TOC, OSI and caspase-3 levels decreased. Conclusion: B significantly reduced testicular lipid per-oxidation and strengthened antioxidant defenses. Our results showed that pre-treatment B can protect rat testis against CP-induced testicular damage owing to its anti-lipid per oxidation, anti-oxidant and anti-apoptotic properties.
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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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    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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    Investigation into the protective effects of Hypericum Triquetrifolium Turra seed against cyclophosphamide-induced testicular injury in Sprague Dawley rats
    (Taylor & Francis Ltd, 2022) Can, Senanur; Yildiz, Songul Cetik; Keskin, Cumali; Sahinturk, Varol; Cengiz, Mustafa; Baskoy, Sila Appak; Ayhanci, Adnan
    For centuries, Turkey has been a significant location here around 80 species of Hypericum with differing names widely occur, which is also known as Turkish folk medicine in treating some bacterial diseases as well as stomach and intestine inflammation. Recent studies have reported this herb family to contain numbers of bioactive compound contents. The study aims to investigate the protective effects of Hypericum triquetrifolium Turra (HT) upon oxidative stress and apoptosis in a rat model in which testes injury was induced by CP. The testicular injury was caused using CP (150mg/kg). The rats were treated with a single dose (100mg/kg) of methanol extract of HT to investigate various biochemical markers in the serum and plasma of blood samples apart from assessing the prognosis of CP-induced testicular damage. Added to that, histological analyses were performed to identify possible structural changes and apoptotic indicators, like Bax, Caspase-3, and Bcl-2. In CP Group, there was a rise in the levels of total oxidant status (TOS), malondialdehyde (MDA), oxidative stress index (OSI), Caspase-3, and Bax while superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), Bcl-2, and total antioxidant capacity (TAC) all decreased. Also, our histological analysis showed damaged testes. On the other hand, neither biochemical nor histological analysis showed testicular damage in HT Alone Group. In CP+HT Group, a significant number of the negatives changes due to CP were observed to have improved remarkably following an HT treatment. This study results suggest that HT could help improve CP-induced testicular injury thanks to its anti-oxidative and anti-apoptotic properties. [GRAPHICS] . HIGHLIGHTS The present study is the first of its kind in the sense that it investigated the effects of Hypericum triquetrifolium Turra (HT) on the testicular injury that is attributable to cyclophosphamide (CP), which is a drug used for chemotherapy. Confocal and light microscopic analyses revealed that HT reduced CP-related oxidative stress, apoptosis, and tissue damage in statistically significant amounts. The antioxidant properties of HT appear to account for the protective effects of HT upon experimentally induced 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.