WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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Article Citation - Scopus: 1Aqueous Parsley (Petroselinum crispum) Extract Ameliorated Methotrexate-Induced Brain and Small Intestine Damage in Rats(Ankara Univ, 2025) Saçan, Ozlem; Şener, Göksel; Yanardag, Refıye; Tunali-Akbay, Tugba; Sivas, Guzin Goksun; Karaoğlu, Sümeyye Yılmaz; Dursun, Ercan; Akbay, Tugba Tunali; Yilmaz Karaoğlu, Sümeyye; Tufan, Elif; Tunali Akbay, TugbaMethotrexate (MTX) is a widely used antiarthritic and chemotherapeutic agent known to cause damage to various tissues. This study investigated the potential protective effects of parsley extract against MTX-induced brain and intestinal tissue damage. Sprague-Dawley rats were divided into control, control + parsley, MTX, and MTX + parsley. MTX (20 mg/kg, i.p.) was administered to the MTX and MTX + parsley groups. The control + parsley, and MTX + parsley groups were administered 2 g/kg parsley extract by oral gavage for five consecutive days. After the fifth day, brain and small intestinal tissues were taken. Total protein, nitric oxide, lipid peroxidation, glutathione levels, tissue factor, superoxide dismutase, and glutathione S-transferase activities were determined in these tissues. The protein profiles of the tissues were evaluated using SDS polyacrylamide gel electrophoresis. Parsley administration caused a decrease in lipid peroxidation levels in both tissues of the MTX group. On the other hand, glutathione level, glutathione-S-transferase, and superoxide dismutase activities were found to be increased. On the other hand, parsley decreased the nitric oxide level which was increased in the intestinal tissues of the MTX group. There was no significant change in brain nitric oxide level and tissue factor activity between groups. MTX and parsley administration altered protein expression, leading to the appearance or disappearance of specific bands in intestinal and brain tissues. In conclusion, parsley alleviated MTX-induced damage in brain and intestinal tissues by reducing lipid peroxidation and modulating antioxidant defenses.Article Citation - WoS: 3Citation - Scopus: 2Morphological and Biochemical Investigation of the Protective Effects of Panax Ginseng on Methotrexate-Induced Testicular Damage(Istanbul Univ, 2023) Karakaya-Cimen, Fatma Bedia; Macit, Caglar; Sivas, Guzin Goksun; Akbay, Tugba Tunali; Sener, Goksel; Ercan, Feriha; Cımen, Fatma Bedia KarakayaObjective: Methotrexate (MTX) is a chemotherapeutic agent that causes testicular toxicity used in the cure of various types of cancer. The anti-oxidant and anti-cancer effects of Panax ginseng (PxG) have been reported in both experimental and clinical studies. This study aims to examine the healing effect of PxG on testicular damage induced by MTX. Materials and Methods: Sprague Dawley male rats (8-week-olds) were used in the study. A single dose ofMTXdissolved in saline (20 mg/kg) was given to MTX and MTX+PxG groups by intraperitoneal injection. PxG dissolved in saline (100 mg/kg) was given by orogastric gavage once a day for 5 days to the MTX+PxG group. Saline was given to the control and MTX groups orally during the experiments. After decapitation, the testis sampleswere obtained. Seminiferous tubules and basement membranewere evaluated histopathologically. Seminiferous tubule diameter and germinal epithelium thickness were measured. Furthermore, oxidative stress parameters such as malondialdehyde, glutathione, superoxide dismutase, and glutathione-S-transferase were measured. Results: MTX treatment caused seminiferous tubule degeneration with a decrease in Johnsen's score, the seminiferous tubule's diameter, and the germinal epithelium's thickness. Parallel with the histopathological results increased testicular oxidative stress with an increase in malondialdehyde level and a decrease of endogenous anti-oxidant activity with a decrease in glutathione level and glutathione-S-transferase and superoxide dismutase activities. PxG treatment improved these histological and biochemical parameters in MTX-induced testis cytotoxicity. Conclusion: MTX treatment causes testicular damage via the oxidative processes. PxG treatment ameliorates MTX-induced testicular damage by inhibiting oxidative stress.Article Panax Ginseng Extract Ameliorates Methotrexate-Induced Multi-Organ Damage Via the Regulation of Oxidative Stress(Marmara Univ, 2023) Macit, Caglar; Ede-Pazarbasi, Seren; Yilmaz-karaoglu, Suemeyye; Tunali-Akbay, Tugba; Karakaya-Cimen, Fatma Bedia; Ercan, Feriha; Sener, Goksel; Akbay, Tugba Tunalı-Oxidative damage plays an important role in organ toxicities caused by methotrexate (MTX). This study aimed to determine the antioxidant effects of Panax ginseng (PxG) extract against MTX-induced liver, lung, ileum and kidney damage. Twenty-four Sprague Dawley male rats (weight 250-300 g) were used in the study. The animals were randomly separated into three groups: a) Control, b) MTX-treated (MTX) and c) MTX+PxG-treated (MTX+PxG) groups. MTX was administered intraperitoneally at 20 mg/kg, as a single dose to MTX and MTX+PxG groups. PxG was administered orally at 100 mg/kg to the MTX+PxG group for five days. Saline was given to the control and MTX groups for 5 days. At the end of the experiment, liver, lung, ileum, and kidney samples were obtained. Malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD), glutathione-S-transferase (GST) and tissue factor (TF) activities were determined in all tissues. In addition, histological examinations were done through light microscopy. GraphPad Prism 5v. was used for statistics, and p<0.05 were considered significant. Administration of MTX caused severe injury in tissues. Findings showed that MDA level, SOD, and GST activities were significantly normalized in the MTX+PxG group compared to the control group. A significant reduction in GSH level observed in the MTX group was reversed with PxG administration In addition, TF activity and total protein levels were found to be impaired in the MTX group, but TF activity was significantly improved in liver and lung tissues and total protein level was significantly reversed in lung and ileum in MTX+PxG group. The results of histological examinations showed that MTX-induced damage was ameliorated with the PxG administration. In conclusion, this study shows that Panax ginseng, thanks to its antioxidant properties, reversed MTX-induced tissue damage and therefore may be beneficial against side effects in patients undergoing chemotherapy.Article Citation - Scopus: 1Protective Effects of <i>momordica Charantia</I> (bitter Melon) Against Methotrexate-Induced Kidney Damage(Bentham Science Publ Ltd, 2023) Macit, Caglar; Ozbeyli, Dilek; Cevik, Ozge; Cetin, Melisa; Sener, Goksel; Ozkan, SevilBackground Methotrexate is a cytotoxic chemotherapeutic agent that has severe side effects, such as nephrotoxicity. Momordica charantia is a bright yellow-orange fruity plant that has been shown to have antioxidant, antidiabetic, and anti-inflammatory properties. Objective This study scrutinized the protective effects of Momordica charantia extract against methotrexate-induced nephrotoxicity. Methods 24 Sprague Dawley male rats were divided into three experimental groups (8 rats in each): Control (C); Methotrexate (MTX); and Methotrexate plus Momordica charantia (MTX+MC). All rats were fed ad libitum and tap water. Methotrexate was administered at 20 mg/kg intraperitoneally as a single dose. In the MTX+MC group, MC was administered at a dose of 50mg/kg for 5 days orally. At the end of the 5th day, the rats were decapitated and kidney samples were taken to analyze glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and caspase-3 activity. Data was analyzed with GraphPad Prism 5.0. Results Findings showed that while there was a significant increase in MDA, MPO, 8-OHdG levels, and an essential reduction in GSH levels in the MTX-treated group when compared with the control group, bitter melon treatment significantly reversed MDA, MPO, and 8-OHdG levels (p< 0.001). GSH level elevation was observed in the MTX-MC group when compared to the MTX-treated group (p< 0.001). Conclusion This study showed that bitter melon is thought to have a protective effect against kidney damage caused by methotrexate. With future studies, we believe that the use of bitter melon extract as a protective agent in kidney damage caused by drug-induced oxidative damage will bring an innovative approach to treatment.Article Citation - WoS: 4Citation - Scopus: 4Whey Protein Concentrate Ameliorates the Methotrexate-Induced Liver and Kidney Damage(Cambridge Univ Press, 2023) Tufan, Elif; Sivas, Guezin Goksun; Gurel-Gokmen, Begum; Yilmaz-Karaoglu, Suemeyye; Dursun, Ercan; Caliskan-Ak, Esin; Tunali-Akbay, Tugba; Yllmaz-Karaoǧlu, SÜmeyye; Çallşkan-Ak, EsinMethotrexate (MTX) is a cytotoxic immunosuppressant that is widely used in the treatment of tumours, rheumatoid arthritis and psoriasis. This study aims to evaluate the effects of whey proteins on MTX-induced liver and kidney damage by focusing on oxidant-antioxidant systems and eating habits. The study was conducted in four groups of thirty Sprague-Dawley rats (control, control + whey protein concentrate (WPC), MTX, MTX + WPC). A single dose of 20 mg/kg MTX was administered intraperitoneally to the MTX groups. Control and MTX groups were given 2 g/kg WPC by oral gavage every day for 10 d. At the end of day 10, blood samples were drawn and liver and kidney tissues were removed. MTX administration increased the lipid peroxidation level and decreased glutathione level, superoxide dismutase and glutathione-S-transferase activities in the liver and kidney. Administration of WPC significantly reduced the damage caused by MTX in the liver and kidney. While a decrease in serum urea level and an increase in serum creatinine level were detected in the MTX group, WPC administration reversed these results up to control group levels. Administration of WPC to the MTX group significantly reversed the histopathological damage scores of the liver and kidney. WPC administration ameliorated the MTX-induced oxidative damage in the liver and kidney tissues due to its antioxidant properties. Liver and kidney damage can be prevented by using whey proteins as a nutraceutical in MTX therapy. In conclusion, whey proteins demonstrated a protective effect against MTX-induced liver and kidney damage.Article Citation - WoS: 1Citation - Scopus: 2The Effect of Whey Proteins on the Brain and Small Intestine Nitric Oxide Levels: Protein Profiles in Methotrexate-Induced Oxidative Stress(Istanbul Univ, 2022) Yilmaz, Sumeyye; Tufan, Elif; Sivas, Guzin Goksun; Gokmen, Begum Gurel; Dursun, Ercan; Ozbeyli, Dilek; Tunali-Akbay, Tugba; Şener, Göksel; Karaoğlu, Sümeyye YılmazObjectives: The aim of this study was to determine the effects of whey proteins on methotrexate (MTX)-induced brain and small intestine damage. Materials and Methods: 30 Sprague Dawley rats (200-300 g) were divided into four groups: Control, control + whey, MTX, and MTX+whey. MTX was administered at 20 mg/kg (single dose) intraperitoneally to the MTX group rats, and 2 mg/kg of whey protein were administered by oral gavage for 10 days to the whey groups. Lipid peroxidation, glutathione, and nitric oxide (NO) levels, as well as glutathione-Stransferase and superoxide dismutase activities were measured in the brain and small intestine. SDS-polyacrylamide gel electrophoresis of the brain and intestine tissues were also carried out. Results: While MTX treatment caused oxidative damage in the brain and small intestine, whey protein administration ameliorated MTXinduced oxidative stress. MTX administration did not change the brain's NO level, while an increase in intestinal NO level was detected. Conclusion: MTX induced oxidative stress in the brain and small intestine changed the protein metabolism in these tissues regardless of reduced food intake. Consecutive 10-day administration of whey proteins has shown its therapeutic effect on MTX-induced brain and small intestine oxidative damage.Article Citation - WoS: 5Citation - Scopus: 7Bitter Melon (Momordica charantia) Fruit Extract Ameliorates Methotrexate-Induced Reproductive Toxicity in Male Rats(Marmara University, 2021) Kanpalta, Fatma; Özbeyli, Dilek; Sen, Ali; Cevik, O. Dağdeviren; Şener, Göksel; Ercan, FerihaObjective: Methotrexate (MTX) is a drug commonly used for the treatment of malign neoplastic and inflammatory diseases. Anti-oxidant and anti-inflammatory effects of bitter melon (BM) were reported. The aim of this study was to examine the effects of BM fruit extract on MTX-induced testicular and epididymal damage. Materials and Methods: Sprague Dawley male rats were divided into three groups (n=8) as control, MTX and MTX+BM. A single dose of MTX (20 mg/kg) was injected intraperitoneally to the MTX and MTX+BM groups. BM fruit extract (600 mg/kg) was applied to the MTX+BM group orally for 5 days. Testes were examined for general histopathology, proliferating and apoptotic cells. The epididymis samples were used for the evaluation of sperm morphology. Oxidative and inflammatory markers were analysed biochemically. Results: Increased abnormal spermatozoa, degenerated seminiferous tubules with increased apoptotic cells and decreased proliferative cells were observed in the MTX group. TNF-α, IL-1β, 8-hydroxy-2-deoxyguanosine and caspase-3 levels increased, superoxide dismutase and catalase levels decreased in both testis and epididymis samples. All these histological and biochemical parameters were ameliorated in the MTX+BM group. Conclusion: Methotrexate causes testis damage by decreasing spermatogenic cells and increasing apoptosis through oxidative stress and inflammation. BM extract improves testis and epididymis damage with its possible anti-oxidant and anti-inflammatory effects. © 2025 Elsevier B.V., All rights reserved.Article Citation - WoS: 1The Protective Effects Of<i> Momordica</I><i> Charantia</I> Fruit Extract in Methotrexate Induced Liver Damage in Rats(Galenos Publ House, 2022) Ozbeyli, Dilek; Sen, Ali; Cevik, Ozge; Erdogan, Omer; Kaya, Ozlem Tugce Cilingir; Ede, Seren; Sener, Goksel; Ede-pazarbasi, Seren; Cilingir-kaya, Ozlem TugceBACKGROUND/AIMS: Methotrexate (MTX), a cytotoxic therapeutic agent, is used for the cure of malignancies and rheumatologic disorders. However, the significant side effects of MTX limits its use. In this study, we aim to assess the hepatoprotective properties of Momordica charantia (MC) against MTX-induced liver damaged in rats.MATERIALS AND METHODS: Following one dose of MTX (20 mg/kg), the rats were given either distilled water or MC extract (300 mg/kg, po) for 5 days. After the dissection of the rats, the liver was removed to analyse tumour necrosis factor -a (TNF-a), interleukin-113 (IL-113), transforming growth factor 13 (TGF-13) and 8-hydroxy-2'-deoxy-guanosine (8-OhdG) levels and superoxide dismutase (SOD), catalase (CAT), and caspase-3 activities. The tissues were also examined histopathologically.RESULTS: The hepatic TNF-a, IL-113, TGF-13, 8-OhdG levels, and Caspase-3 activity in the MTX group were found to be significantly increased compared to the control group. However, MC extract was able to significantly decrease TNF-a, TGF-13, 8-OhdG levels, and Caspase-3 activity. Also, both the SOD and CAT activity of the MTX group decreased compared to the control group. Although only the SOD levels elevated significantly with MC treatment, the SOD and CAT activities of the MC treated group were similar to the control group. Supporting these biochemical parameters, MTX-induced histologic alterations in the liver were also ameliorated via MC treatment.CONCLUSION: Our results demonstrated that MC has a protective role against MTX-induced hepatic tissue injury by reducing apoptosis, oxidative damage, and the expression of pro-inflammatory cytokines.Article Citation - WoS: 5Citation - Scopus: 5Inhibitory Effect of Whey Protein Concentrate on Sars-Cov Furin Activity and Spike Protein-Ace2 Binding in Methotrexate-Induced Lung Damage(Wiley-hindawi, 2022) Tufan, Elif; Sivas, Guzin Goksun; Gurel-Gokmen, Begum; Yilmaz-Karaoglu, Sumeyye; Ercan, Dursun; Ozbeyli, Dilek; Tunali-Akbay, TugbaThis study aims to investigate the effects of whey proteins on SARS CoV-2 in methotrexate-induced lung tissue damage in rats. To determine the possible effects, rats were divided into four groups as control, control + whey, methotrexate (20 mg/kg, i.p.) and methotrexate + whey. Whey protein concentrate (2 g/kg, oral gavage) was administered for 10 days. Cytokine levels were measured and protein electrophoresis was carried out in serum samples. Lipid peroxidation, nitric oxide and glutathione level, and superoxide dismutase and glutathione S transferase activities were determined in lung samples. Inhibition of SARS CoV-2-targeted lung furin activity and SARS CoV-2 spike protein-angiotensin converting enzyme binding with whey protein concentrate were also measured in each group. In conclusion, whey protein concentrate improved methotrexate-induced lung damage and inhibited lung furin activity targeting SARS-CoV-2 S1/S2 site cleavage and SARS CoV-2 spike protein-angiotensin converting enzyme binding. Whey proteins are potential protective candidates that inhibit SARS CoV-2-related interactions, even in methotrexate-induced lung injury. Practical applications Whey proteins have anticarcinogenic, antihypertensive, antioxidant, antibacterial, antiviral, and immunomodulating properties due to the protein, bioactive peptide, and essential amino acid content. Methotrexate is a folate antagonist and inhibits cell proliferation and purine synthesis. The combined use of whey protein concentrate and methotrexate may be an alternative in the development of new strategies to the treatment approaches against COVID-19. In addition, according to the results of this study, it is thought that the protective effect of whey proteins in healthy conditions before encountering the SARS CoV-2 may be higher than those who have never used it.
