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    Crocin suppresses inflammatory response in LPS-induced acute lung injury (ALI) via regulation of HMGB1/TLR4 inflammation pathway
    (Dokuz Eylül University institute of health sciences, 2024) Ceylan, Tayfun; Akın, Ali Tuğrul; Kaymak, Emin; Varinli, Saban; Toluk, Ayşe
    Purpose: The most significant pathogen hypothesized to be causing the formation of Acute lung injury (ALI) in sepsis is thought to be lipopolysaccharide (LPS), a key endotoxin component of gram-negative bacteria. The main objective of this study is to determine possible anti-inflammatory effects of crocin (CRO) which has many biological properties such as anti-inflammatory, antioxidant, and anti-apoptotic in LPS-induced ALI. Material and Methods: 40 Wistar albino rats were divided into four groups: Control (no treatment), CRO (given 50 mg/kg crocin for 9 days), LPS (given 30 mg/kg LPS at 9th day), LPS+CRO (given 50 mg/kg crocin for 9 days and 30 mg/kg LPS at 9th day). After experimental, rats were sacrificed and lungs were extracted. Histological examinations were performed in the lung tissue and the changes in the HMGB1 and TLR4 expressions were determined via immunohistochemical staining. Results: Hemorrhage, HMGB1 and TLR4 expressions significantly increased in the LPS group. However, CRO administrations exerted a strong protective effect on the lungs in terms of these parameters in LPS+CRO group. Conclusion: According to our results, we suggest that CRO can be considered as a protective agent against LPS induced ALI via inhibition of HMGB1/TLR4 pathway-mediated inflammatory response.
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    Crocin Suppresses Inflammatory Response in LPS-Induced Acute Lung Injury (ALI) Via Regulation of HMGB1/TLR4 Inflammation Pathway
    (Dokuz Eylul University, 31 Mayıs 2024) Ceylan, Tayfun; Akın, Ali; Kaymak, Emin; Varinli, Şaban; Toluk, Ayşe
    Background and Purpose: The most significant pathogen hypothesized to be causing the formation of Acute lung injury (ALI) in sepsis is thought to be lipopolysaccharide (LPS), a key endotoxin component of gram-negative bacteria. The main objective of this study is to determine possible anti-inflammatory effects of crocin (CRO) which has many biological properties such as anti-inflammatory, antioxidant, and anti-apoptotic in LPS-induced ALI. Methods: 40 Wistar albino rats were divided into four groups: Control (no treatment), CRO (given 50 mg/kg crocin for 9 days), LPS (given 30 mg/kg LPS at 9th day), LPS+CRO (given 50 mg/kg crocin for 9 days and 30 mg/kg LPS at 9th day). After experimental, rats were sacrificed and lungs were extracted. Histological examinations were performed in the lung tissue and the changes in the HMGB1 and TLR4 expressions were determined via immunohistochemical staining. Results and Conclusion: Hemorrhage, mononuclear cell infiltration and HMGB1 and TLR4 expressions significantly increased in the LPS group. However, CRO administrations exerted a strong protective effect on the lungs in terms of these parameters in LPS+CRO group. According to our results, we suggest that CRO can be considered as a protective agent against LPS induced ALI via inhibition of HMGB1/TLR4 pathway-mediated inflammatory response.
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    Effect of vitamin B12 on methotrexate-induced cardiotoxicity in rats
    (Mashhad Univ Med Sciences, 2024) Kuloglu, Nurhan; Karabulut, Derya; Kaymak, Emin; Akin, Ali Tugrul; Ceylan, Tayfun; Yildirim, Aysegul Burcin; Yakan, Birkan
    Objective(s): Methotrexate (MTX) is a drug with anti-inflammatory and immunosuppressive effects and is also a folic acid antagonist. Our aim in this study is to determine the molecular mechanisms of cardiotoxicity caused by MTX, a chemotherapeutic drug, and to evaluate the protective effects of vitamin B12 on this toxicity. Materials and Methods: A total of 32 rats were used in our study and 4 groups were formed. Control group, Vit B12 group (3 mu g/kg B12 for 15 days, IP), MTX group (20 mg/kg MTX single dose on day 8 of the experiment, IP), MTX +Vit B12 group (3 mu g/kg, IP ), Vit B12 throughout the 15 days, and a single dose of 20 mg/kg MTX (IP) on day 8 of the experiment. Immunohistochemically, expressions of hypoxia-inducible factor 1 alpha (HIF1-alpha), vascular endothelial growth factor receptor -2 (VEGFR-2), erythropoietin (EPO), and interleukin-6 (IL -6) were evaluated in the heart tissue. Total catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured in the heart tissue. At the same time, ANP and NT-proBNP levels were measured in the blood serum. Results: In the study, the expression of HIF1-alpha and VEGFR-2 increased significantly in the MTX group, while IL -6 and EPO significantly decreased. At the same time, CAT and SOD levels were significantly decreased and MDA levels increased significantly in the MTX group. While vitamin B12 significantly corrected all these values, it also greatly reduced the increases in ANP and NT-proBNP levels caused by MTX. Conclusion: It is important to use Vit B12 before and after MTX administration to replace the folate that MTX has reduced.
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    Investigation of the effect of thymoquinone on kidney damage in isoproterenol-induced myocardial infarction in rats and cardiorenal interactions
    (Gaziantep İslam Bilim ve Teknoloji Üniversitesi, 30 Kasım 2023) Yıldırım, Ayşegül Burçin; Değer, Necla; Sayan, Meryem; Akın, Ali; Ceylan, Tayfun; Kaymak, Emin; Kara, Mehmet; Ünsal, Murat
    This study aimed to determine whether thymoquinone has any protective effects on renal tissue after an isoproterenol-induced myocardial infarction (MI). Experimental groups were formed as 4 groups (n=8). Control group (C). Thymoquinone group (THQ), 20 mg/kg single dose intragastric (i.g.) daily for seven days. Isoproterenol group (ISO) was administered 100 mg/kg intraperitoneally in two doses on days 7 and 8 of the experiment. Thymoquinone+Isoproterenol group (THQ+ISO), THQ 20 mg/kg i.g. was administered once a day for seven days. In addition, two doses of ISO 100 mg/kg i.p. were administered on the seventh and eighth days. Kidney tissues were evaluated histopathologically. Kidney tissues were evaluated histopathologically. Tumour necrosis factor alpha(TNF-α) and alpha Smooth Muscle Actin(α-SMA) immunoreactivity density changes were determined by immunohistochemistry. Glutathione(GST), Glutathione S-transferases(GSTs) and Interleukin-6(IL-6) levels were evaluated by ELISA method. Isoproterenol injection caused severe histopathological changes on kidney tissue. Also TNF-α and α-SMA levels were found to be higher in groups where ISO was administered. THQ could be effective on kidney tissue to partially correct these histopathological damages, by decreasing fibrosis and inflammation. This study shows that treatment with THQ is effective in preventing kidney damage caused by ISO-induced MI. We think that THQ as a supplementary food will be effective to prevent kidney damage.
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    Protective effect of melatonin on cisplatin induced acute kidney injury: Role of regulation of heat shock proteins expressions
    (Natl Inst Science Communication-Niscair, 2023) Akin, Ali Tugrul; Unsal, Murat; Ceylan, Tayfun; Kaymak, Emin; Ozturk, Emel; Kuloglu, Nurhan; Karabulut, Derya
    Chemotherapy is one of the major treatment approaches for cancer, and these agents are known to cause severe side effects, including damaging vital organs. Cisplatin (CP) is a commonly used chemotherapeutic agent in the treatment of many cancer types, particularly lung, breast, ovarian, testicular and head-neck cancers. CP is reported to cause damage to damage on brain, kidney, liver and gonads. In this study, is we investigated the protective effects of melatonin (MEL) in acute kidney injury (AKI) induced by CP via assessment of heat-shock protein (HSP) induction in rats. For this purpose, total 40 Wistar albino rats were divided into four groups: Control (n=10), MEL (n=10, 10 mg/kg/i.p. melatonin for 8 days), CP (n=10, 7 mg/kg/i.p. cisplatin at the 5th day), and CP+MEL (n=10, 10 mg/kg/i.p. melatonin for 8 days and 7 mg/kg/i.p. cisplatin at the 5th day). After kidney tissues were extracted, histopathological changes were evaluated and immunoreactivities of HSP47, HSP60, HSP70 and HSP90 in renal cortex were detected via immunohistochemistry. Moreover, blood serum BUN (blood urea nitrogen), creatinine and uric acid levels were measured to assess kidney function. CP group showed histopathological deterioration, and MEL treatment attenuated this damage in CP+MEL group. An increase in HSPs immunoreactivities were detected in renal cortex of CP group when compared with the control and MEL groups, showing increased HSP response because of CP-induced AKI. However, CP-induced HSP induction was significantly lower in the CP+MEL group. Similarly, blood serum BUN, creatinine and uric acid levels were higher in CP group while CP+MEL group showed decreased levels of these parameters. Our results suggest that MEL could exert a significant protective effect against CP-induced AKI via reducing HSP response.
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    Thymoquinone reduces methotrexate-induced heart damage: a histopathological study in rats
    (Cukurova Univ, Fac Medicine, 2023) Yildirim, Aysegul Burcin; Kaymak, Emin; Ceylan, Tayfun; Akin, Ali Tugrul; Kuloglu, Nurhan; Sayan, Meryem; Deger, Necla
    Purpose: The study aimed to evaluate the effect of thymoquinone on cardiac tissue in MTX-induced cardiac toxicity in rats with various parameters.Materials and Methods: Group I (n=8) was administered intraperitoneal saline for 10 days. Intraperitoneal olive oil was applied to Group II (n=8) for 10 days. Group III (n=8) received 10 mg/kg Thymoquinone (THQ) intraperitoneally for 10 days. Group IV (n=8) was administered a single dose of 20 mg/kg Methotrexate (MTX), 500 mg/20 ml, intraperitoneally on the 1st day of the experiment. Group V (n=8) MTX: 20 mg/kg single dose intraperitoneally on the 1st day; THQ: 10mg/kg i.p. administered for 10 days. Since Methotrexate was in liquid form, no solvent was used. At the end of the experimental period, the rats were sacrificed for analysis of heart tissue. The structure of heart tissue was evaluated by hematoxylin-eosin staining. Immunohistochemically, Connexin-43, HSP90, and HIF- 1 alpha antibodies were stained.Results: Group IV was found to have histopathological deterioration, which was ameliorated by THQ. In addition to this; Connexin-43 immunoreactivity was the lowest in Group IV compared to other groups: 108.5 +/- 7.4. Compared to other groups, HSP90 immunoreactivity was highest in Group IV: 103.6 +/- 10.4. Compared to other groups, HIF-1 alpha immunoreactivity was highest in Group IV: 95.2 +/- 9.1.Conclusion: Thymoquinone has a positive effect on Connexin-43, one of the proteins providing conduction in intercalary discs, HSP90, one of the chaperones in the cell and HIF-1 alpha expression against MTX toxicity. At the same time, THQ provides a significant improvement in cardiac tissue histopathologically by showing a cardioprotective effect.