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    Bisphenol AF Caused Reproductive Toxicity in Rats and Cineole Co-Treatment Exhibited Protective Effect
    (Springer Heidelberg, 2024) Uyar, Ahmet; Cellat, Mustafa; Kanat, Ozgur; Etyemez, Muhammed; Kutlu, Tuncer; Deveci, Mehmet Zeki Yilmaz; Yavas, Ilker
    Bisphenol AF (BPAF) is increasingly used and now found in products intended for human consumption. The protective effect of 1,8-cineole (CIN) against BPAF-induced reproductive toxicity was investigated. Four groups were created, with each group consisting of eight rats: control, BPAF (200 mg/kg), CIN (200 mg/kg), and BPAF + CIN groups. The results demonstrated that the BPAF group exhibited a decline in testosterone levels and a decrease in sperm parameters compared with the control. Additionally, higher levels of MDA were observed, along with lower levels of GSH and GPx activity. CAT activity also decreased slightly. Tnf-alpha, Nf-kappa B levels were significantly higher, and caspase-3 expression was elevated, while PCNA expression decreased. BPAF significantly increased tissue degeneration compared with the control. However, the BPAF + CIN group showed statistically significant improvements in sperm parameters, except for concentration. They also exhibited an increase in testosterone levels and an improvement in MDA and GSH levels compared with the BPAF group. However, GPx activity partially enhanced. Tnf-alpha and Nf-kappa B levels were significantly reduced, and caspase-3 levels declined while PCNA and Bcl-2 levels increased. The Johnsen Testicular Biopsy score showed a substantial increase. Overall, these results suggest that CIN co-treatment in rats enhanced reproductive health and exhibited antioxidant, antiapoptotic, and anti-inflammatory properties against BPAF-induced testicular damage.
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    Carvacrol showed a curative effect on reproductive toxicity caused by Bisphenol AF via antioxidant, anti-inflammatory and anti-apoptotic properties
    (Pergamon-Elsevier Science Ltd, 2023) Uyar, Ahmet; Cellat, Mustafa; Kanat, Ozgur; Etyemez, Muhammed; Kutlu, Tuncer; Deveci, Mehmet Yilmaz Zeki; Yavas, Ilker
    Bisphenol AF (BPAF) is an endocrine disruptor, and human exposure to these chemicals is growing in industrialized nations. BPAF has been demonstrated in studies to have toxic effects on reproductive health. This study examined the effects of oral exposure to BPAF on the reproductive system and the protective effects of carvacrol in rats. From 32 Wistar albino rats, four separate groups were set up for this purpose. Carvacrol 75 mg/kg and BPAF 200 mg/kg were administered by oral gavage method. Rat sperm parameters and serum testosterone levels were measured after 28 days of administration. The study looked at the MDA in the testis tissues, as well as CAT, GPx, and GSH as antioxidants parameters, NF-& kappa;B and TNF-& alpha; as inflammatory markers, caspase-3 and Bcl-2 as apoptosis parameters, and PCNA as cell proliferation markers. In addition, testis tissues underwent histological evaluation. As a result, in rats exposed to only BPAF, sperm counts declined, testosterone levels reduced, oxidative stress, inflammation, and apoptosis increased, and cell proliferation decreased. Furthermore, severe disruptions in tissue architecture and decreased spermatogenesis were reported. In contrast, sperm parameters improved, testosterone levels increased, oxidative stress and inflammation decreased, and apoptosis was prevented in the carvacrol-treated group compared to the BPAF-only group. It was also found that spermatogenesis was maintained, and structural abnormalities in testicular tissue were mostly avoided with an increase in PCNA expression. According to the findings, despite BPAF-induced testicular and reproductive toxicity, carvacrol had therapeutic potential due to its anti-inflammatory, antioxidant, cell proliferation-increasing, and anti-apoptotic activities.
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    The effect of tyrosol on diclofenac sodium-induced acute nephrotoxicity in rats
    (Wiley, 2024) Comez, Mehmet; Cellat, Mustafa; Kuzu, Muesluem; Uyar, Ahmet; Turk, Erdinc; Kaya, Yusuf Selim; Etyemez, Muhammed
    Although diclofenac (DCF) is a nonsteroidal anti-inflammatory drug that is considered safe, its chronic use and overdose may show some toxic effects. The protective effect of tyrosol (Tyr) pretreatment against DCF-induced renal damage was investigated in this study. The 32 rats used in the study were randomly divided into four groups of eight rats each. According to the data obtained, it was determined that creatinine, urea, and blood urea nitrogen (BUN) levels increased in serum samples of the DCF group. Besides, the levels of reduced glutathione (GSH) and glutathione peroxidase (GPx) activity decreased and the malondialdehyde (MDA) level increased in the kidney tissue. However, no change was observed in catalase (CAT) activity. Cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-kappa B), and tumor necrosis factor-alpha (Tnf-alpha) levels increased and nuclear factor erythroid 2-related factor 2 (Nrf-2) levels decreased. No change was detected in the level of interleukin 1 beta (IL-1 beta). When the DCF+Tyr group and the DCF group were compared, it was assessed that Tyr had a curative effect on all biochemical parameters. Also, kidney damages, such as degeneration and necrosis of tubular epithelium and congestion of veins, were obviated by treatment with tyrosol in histopathological examinations. It was determined that Tyr pretreatment provided a protective effect against nephrotoxicity induced by DCF with its anti-inflammatory and antioxidant properties.
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    The protective effect of esculetin against aluminium chloride-induced reproductive toxicity in rats
    (Wiley, 2021) Turk, Erdinc; Ozan Tekeli, Ibrahim; Ozkan, Huseyin; Uyar, Ahmet; Cellat, Mustafa; Kuzu, Muslum; Yavas, Ilker
    One of the prominent health problems caused by Aluminium was the decrease in male fertility rates. In the study, the protective effect of Esculetin (ESC) against the reproductive toxicity induced by Aluminium chloride (AlCl3) was investigated. For this purpose, AlCl3 was administrated to Wistar Albino rats at a dose of 34 mg/kg and ESC was administrated at a dose of 50 mg/kg for 70 days. It was determined that AlCl3 treatment reduced sperm motility and concentration, increased dead/live rate and abnormal sperm rate. It decreased serum testosterone level, and co-treatment of ESC significantly regulated these values. In the AlCl3-treated group, MDA level increased and GSH level, GPx and CAT activities decreased compared with those of the control group. However, co-treatment of ESC showed an amelioratory effect on the values except for CAT activity. It was observed that the expression level of NRF-2 increased in the ESC and AlCl3 + ESC groups, and NF-kappa B increased in the AlCl3 group with the control group. It was determined that Caspase-3 expression decreased, and Bcl-2 expression increased in AlCl3 + ESC group compared to AlCl3 group. It was also determined that AlCl3-induced tissue injury was significantly prevented by ESC co-treatment.
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    Protective effect of Smilax excelsa L. pretreatment via antioxidant, anti-inflammatory effects, and activation of Nrf-2/HO-1 pathway in testicular torsion model
    (Wiley, 2022) Cellat, Mustafa; Isler, Cafer Tayer; Uyar, Ahmet; Kuzu, Muslum; Aydin, Tuba; Etyemez, Muhammed; Turk, Erdinc
    The protective effects of the ethanol extract of Smilax excelsa L. (SE) leaves were investigated on testicular tissue of rats with a torsion model in this study. The chemical composition of the extract was detected by means of liquid chromatography with tandem mass spectrometry (LC-MS/MS). SE extract was given for 21 days before torsion was created in the treatment group. The sperm parameters of the torsion group were impaired, and there was an increase in MDA level as well as a decrease in GSH level and GPx activity compared to the control group. TNF-alpha and NF-kappa B levels in the torsion group increased as compared to those in the control group. The expression levels of Nrf-2 and HO-1 were lower in the torsion group than those in the control group. The SE pretreatment group has improved sperm, oxidative stress, and inflammatory markers when compared to the torsion group, and the Nrf-2/HO-1 pathway was activated. Practical applications Smilax excelsa L. is a plant with economic value used in traditional medicine in the treatment of stomachache, bloating, and breast cancer in Northwest Anatolia. It has an antioxidant effect due to the flavonoids and anthocyanins it contains. The protective effect against ischemia-reperfusion-induced tissue and reproductive damage in testicular tissue were demonstrated with the study. When the histological examinations of the tissues were evaluated, it was found that morphological structure of the tissues was retained in the treatment group. The findings indicate that SE prevents tissue damage in the torsion model by antioxidant and anti-inflammatory effects and activating Nrf-2/HO-1 pathway.
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    Tyrosol improves ovalbumin (OVA)-induced asthma in rat model through prevention of airway inflammation
    (Springer, 2021) Cellat, Mustafa; Kuzu, Muslum; Isler, Cafer Tayer; Etyemez, Muhammed; Dikmen, Nursel; Uyar, Ahmet; Gokcek, Ishak
    Asthma is an inflammatory disease that affects many people around the world, especially persons at paediatric age group. The effectiveness of tyrosol, a natural phenolic compound, was examined in the asthma model induced by ovalbumin (OVA). For this purpose, four groups, each consisting of eight rats, were arranged. For 21 days, physiological saline solution was treated to the control group and OVA was treated to the groups of OVA, OVA + dexamethasone (Dexa) and OVA + tyrosol groups, intraperitoneally and through inhalation. Additionally, 0.25 mg/kg Dexa was treated to the OVA + Dexa group and 20 mg/kg tyrosol to the OVA + tyrosol group by oral gavage. Serum, blood, bronchoalveolar lavage fluid (BALF) and lung tissues of the rats were examined. It was observed that MDA level decreased, GSH level and GPx activity increased, and there was no change in CAT activity in lung tissues of the tyrosol treatment groups. It was also observed that NF-kappa B, TNF-alpha, IL-4, IL-5, IL-13, IFN-gamma and IgE levels decreased compared to the OVA group in lung tissue and serum samples except for serum NF-kappa B and IL-4. However, no effect on IL-1 beta level was observed. In addition, it was determined that tyrosol treatment increased the IL-10 level on both tissue samples. The results of the histopathological investigation of lung tissue showed that tyrosol significantly ameliorated OVA-induced histopathological lesions. Additionally, PAS staining showed that mucus hypersecretion was significantly reduced with the use of tyrosol. In addition, it was determined that the number of eosinophils decreased significantly in blood and BALF samples. The obtained results showed that tyrosol possessed antioxidant and anti-inflammatory features on OVA-induced rats and preserved tissue architecture.
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    Tyrosol improves ovalbumin (OVA)-induced asthma in rat model through prevention of airway inflammation (Jul, 10.1007/s00210-021-02117-y, 2021)
    (Springer, 2021) Cellat, Mustafa; Kuzu, Muslum; Isler, Cafer Tayer; Etyemez, Muhammed; Dikmen, Nursel; Uyar, Ahmet; Gokcek, Ishak
    [No abstract available]
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    Zingerone protects liver and kidney tissues by preventing oxidative stress, inflammation, and apoptosis in methotrexate-treated rats
    (Taylor & Francis Ltd, 2022) Turk, Erdinc; Guvenc, Mehmet; Cellat, Mustafa; Uyar, Ahmet; Kuzu, Muslum; Aggul, Ahmet Gokhan; Kirbas, Akin
    The clinical use of drugs used in the treatment of diseases is limited due to the toxic side effects, and many studies have been conducted to benefit from herbal adjuvant therapies recently to eliminate these effects. In this study, the protective effect of zingerone against liver and kidney damage generated in rats through methotrexate (MTX). Histopathological investigations were performed to determine tissue damage caused by MTX and the healing effect of zingone and liver function markers such as serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and renal function markers such as urea, creatine, and aquaporin-1 (AQP-1) were measured. The effects of MTX and protective properties of zingerone on oxidative stress were investigated through the measurement of malondialdehyde and reduced glutathione (GSH) levels, catalase (CAT), and glutathione peroxidase (GPx) enzyme activities. The anti-inflammatory effect of zingerone was determined by measuring the cytokine levels causing inflammation such as nuclear factor-kappa B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), and its effects on apoptosis were determined by immunohistochemical analysis of caspase-3 and B-cell lymphoma-2 (Bcl-2) expression levels. According to the results obtained within the scope of the study, it was determined that zingerone treatment prevented the increase in MTX-induced liver and kidney function markers, showed healing effects on antioxidant parameters degraded in both tissues, and decreased the inflammation parameters. It was determined that it also prevented apoptosis and possessed a protective effect on disrupted tissue architecture by decreasing the increased caspase-3 expression and increasing the decreased Bcl-2 level.