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EŞREFOĞLU, MUKADDES

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MUKADDES
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EŞREFOĞLU
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2012 - 20198
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    PublicationOpen Access
    Investigation of dose-dependent effects of berberine against renal ischemia/reperfusion injury in experimental diabetic rats
    (2019-01-01) Kanbay, Songül; KUMAŞ, MELTEM; EŞREFOĞLU, MUKADDES; Karataş, Ersin; Duymaç, Nurcihan; ERGÜN, İLYAS SAMET; ÜYÜKLÜ, MEHMET; KOÇYİĞİT, ABDÜRRAHİM; KUMAŞ, MELTEM; EŞREFOĞLU, MUKADDES; ERGÜN, İLYAS SAMET; ÜYÜKLÜ, MEHMET; KOÇYİĞİT, ABDÜRRAHİM
    Background: Ischemia-reperfusion injury causes various severe morphological and functional changes in diabetic patients. To date, numerous antidiabetic and antioxidant agents have been used for treatment of the disease-related changes. Objectives: We aimed to examine effective therapeutic doses or doses of berberine against renal ischemia/reperfusion injury (IRI) in a streptozotocin (STZ)-induced diabetic rat model by histopathological and biochemical analysis. Methods: Thirty male Sprague Dawley rats were treated with STZ injection for the development of diabetes, and divided into the following groups: STZ-induced diabetic group (STZ); IRI-induced diabetic group (STZ+IRI); 50mg/kg berberine (BRB) treated diabetic group after inducing IRI (STZ+IRI+BRB1); 100mg/kg BRB treated diabetic group after IRI (STZ+IRI+BRB2); 150mg/kg BRB treated diabetic group after IRI (STZ+IRI+BRB3). Bilateral renal ischemia model was applied for 45min, then reperfusion was allowed for 14 days in STZ-induced diabetic rats. Renal injury was detected histopathologically. Blood urea nitrogen (BUN), creatinine and lactate dehydrogenase (LDH) levels were measured in serum using the ELISA method. Total antioxidant status (TAS) and total oxidant status (TOS) of renal tissue was studied by spectrophotometric assay. Oxidative stress index (OSI) was calculated as TOS-to-TAS ratio. Tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), Na+/K+-ATPase (sodium pump), and Ca2+-ATPase (calcium ATPase) enzyme levels were measured in tissues using the ELISA method. Anti-apoptotic Bax and pro-apoptotic Bcl-2 protein levels were detected by Western blot analysis. All data were evaluated statistically. Results: The highest histopathological score was detected in the STZ+IRI group compared to the other group. BRB administration at the doses of 100mg/kg and 150mg/kg markedly improved renal injury. BUN and creatinine levels significantly increased in the STZ+IRI group compared to the STZ group (p<0.001). 100mg/kg and 150mg/kg BRB administration significantly decreased those levels (p<0.01). The highest TOS and the lowest TAS levels were detected in the STZ+IRI group (p<0.001). IRI markedly aggravated inflammation via increasing levels of TNF-α and CRP (<0.001), and caused apoptosis via inducing Bcl-2 protein, and suppressing Bax protein (p<0.001). BRB administration at the doses of 100mg/kg and 150mg/kg showed anti-oxidant, anti-inflammatory and anti-apoptotic effects (p<0.01). The LDH enzyme, was used as a necrosis marker, was higher in the STZ+IRI group than other groups. BRB administration at all of the doses, resulted in the decline of LDH enzyme level (p<0.001). Ca2+-ATPase and Na+/K+-ATPase enzyme activities decreased in the STZ+IRI group compared to the STZ group (p<0.001), while BRB administration at the doses of 100mg/kg and 150mg/kg significantly increased those of enzyme activities, respectively (p<0.05). Conclusion: Ischemia with diabetes caused severe histopathological and biochemical damage in renal tissue. The high doses of berberine markedly improved histopathological findings, regulated kidney function via decreasing BUN and creatinine levels, and rearranged intercellular ion concentration via increasing Na+/K+-ATPase and Ca2+- ATPase levels. Berberine showed anti-oxidant, anti-apoptotic, and anti-inflammatory effects. According to these data, we suggest that berberine at the doses of 100 and 150mg may be used as a potential therapeutic agent to prevent renal ischemic injury.
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    PublicationOpen Access
    Experimental and clinical evidence of antioxidant therapy in acute pancreatitis
    (2012-10-21) Esrefoglu, MUKADDES; EŞREFOĞLU, MUKADDES
    Oxidative stress has been shown to play an important role in the pathogenesis of acute pancreatitis (AP). Antioxidants, alone or in combination with conventional therapy, should improve oxidative-stress-induced organ damage and therefore accelerate the rate of recovery. In recent years, substantial amounts of data about the efficiency of antioxidants against oxidative damage have been obtained from experiments with rodents. Some of these antioxidants have been found beneficial in the treatment of AP in humans; however, at present there is insufficient clinical data to support the benefits of antioxidants, alone or in combination with conventional therapy, in the management of AP in humans. Conflicting results obtained from experimental animals and humans may represent distinct pathophysiological mechanisms mediating tissue injury in different species. Further detailed studies should be done to clarify the exact mechanisms of tissue injury in human AP. Herein I tried to review the existing experimental and clinical studies on AP in order to determine the efficiency of antioxidants. The use of antioxidant enriched nutrition is a potential direction of clinical research in AP given the lack of clues about the efficiency and safety of antioxidant usage in patients with AP
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    PublicationOpen Access
    Role of stem cells in repair of liver injury: experimental and clinical benefit of transferred stem cells on liver failure.
    (2013-10-28) Esrefoglu, MUKADDES; EŞREFOĞLU, MUKADDES
    Although the liver has a high regenerative capacity, as a result of massive hepatocyte death, liver failure occurs. In addition to liver failure, for acute, chronic and hereditary diseases of the liver, cell transplantation therapies can stimulate regeneration or at least ensure sufficient function until liver transplantation can be performed. The lack of donor organs and the risks of rejection have prompted extensive experimental and clinical research in the field of cellular transplantation. Transplantation of cell lineages involved in liver regeneration, including mature hepatocytes, fetal hepatocytes, fetal liver progenitor cells, fetal stem cells, hepatic progenitor cells, hepatic stem cells, mesenchymal stem cells, hematopoietic stem cells, and peripheral blood and umbilical cord blood stem cells, have been found to be beneficial in the treatment of liver failure. In this article, the results of experimental and clinical cell transplantation trials for liver failure are reviewed, with an emphasis on regeneration. © 2013 Baishideng. All rights reserved. Key words: Liver regeneration; Liver failure; Stem cell Core tip: Although the liver has a high regenerative capacity, as a result of massive hepatocyte death, liver failure occurs. In recent years, there has been extensive experimental and clinical research in the field of cellular transplantation. Transplantation of cell lineages involved in liver regeneration, including mature and fetal hepatocytes, fetal liver progenitor and stem cells, hepatic progenitor and stem cells, mesenchymal stem cells, hematopoietic stem cells, and peripheral blood and umbilical cord blood stem cells, have been found to be beneficial for treating of liver failure. Herein, I review the results of experimental and clinical cell transplantation trials for liver failure.
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    PublicationOpen Access
    Effect of caffeic acid phenethyl ester on bone formation in the expanded inter-premaxillary suture.
    (2015-12-21) KAZANCIOGLU, HO; AKSAKALLI, S; EZIRGANLI, S; BIRLIK, M; Esrefoglu, MUKADDES; ACAR, AH; EŞREFOĞLU, MUKADDES
    Background: Narrow maxilla is a common problem in orthodontics and dentofacial orthopedics. To solve this problem, a procedure called rapid maxillary expansion (RME) has been used. However, relapse tendency is a major problem of RME. Although relapse tendency is not clearly understood, various treatment procedures and new applications have been investigated. The present study aimed to investigate the possible effectiveness of caffeic acid phenethyl ester (CAPE) on new bone formation in rat midpalatal suture after RME. Materials and methods: Twenty male Sprague Dawley rats were used in this study. The animals were randomly divided into two groups as control and CAPE group. In the CAPE group, CAPE was administered systemically via intraperitoneal injection. RME procedure was performed on all animals. For this purpose, the springs were placed on the maxillary incisors of rats and activated for 5 days. After then, the springs were removed and replaced with short lengths of rectangular retaining wire for consolidation period of 15 days. At the end of the study, histomorphometric analysis was carried out to assess new bone formation. Results: New bone formation was significantly greater in the CAPE group than the control group (P<0.05). CAPE enhances new bone formation in midpalatal suture after RME. Conclusion: These results show that CAPE may decrease the time needed for retention.
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    PublicationOpen Access
    Can Coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage?
    (2016-09-01) OZCAN, PINAR; Ficicioglu, Cem; Kizilkale, Ozge; Yesiladali, Mert; Tok, OLGU ENİS; Ozkan, Ferda; Esrefoglu, MUKADDES; ÖZCAN, PINAR; TOK, OLGU ENİS; EŞREFOĞLU, MUKADDES
    Purpose: We investigated antioxidant effects of CoQ10 supplementation on the prevention of OS-induced ovarian damage and to evaluate the protective effect of such supplementation against OS-related DNA damage. Methods: Twenty-four adult female Sprague-Dawley rats were randomly divided into three groups (8 rats per group): group 1 (control): saline, ip, and orally; group 2 (cisplatin group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days; and group 3 (cisplatin + CoQ10 group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days, and 24 h before cisplatin, 150 mg/kg/day orally in 1 mL of saline daily for 14 days. Serum concentrations of anti-Mullerian hormone (AMH), number of AMH-positive follicles, the assessment of the intensity of 8'OHdG immunoreactivity, the primordial, antral and atretic follicle counts in the ovary were assessed. Result(s): The mean serum AMH concentrations were 1.3 ± 0.19, 0.16 ± 0.03, and 0.27 ± 0.20 ng/mL in groups 1, 2, and 3, respectively (p < 0.01). Serum AMH levels were significantly higher in group 1 compared to groups 2 and 3 (p < 0.01 and p = 0.01, respectively). There was a statistically significant difference in AMH-positive follicle count between the groups (p < 0.01). Group 1 showed higher numbers of AMH-positive granulosa cells compared to group 2 (p = 0.01). A significant difference was found in the primordial, the atretic, and antral follicle counts between the three groups (p < 0.01, p < 0.01, and p < 0.01, respectively). The atretic follicle count was significantly lower in the cisplatin plus CoQ10 group compared to the cisplatin group (p < 0.01). The antral follicle counts were significantly higher in the cisplatin plus CoQ10 group compared with the cisplatin group (p < 0.01). There was a statistically significant difference in the intensity of staining of the follicles that were positive for anti-8'OHdG between the groups (p = 0.02). Group 1 showed a significant lower intensity of staining of the follicles positive for anti-8'OHdG compared with group 2 (p = 0.03). Conclusion(s): CoQ10 supplementation may protect ovarian reserve by counteracting both mitochondrial ovarian ageing and physiological programmed ovarian ageing although the certain effect of OS in female infertility is not clearly known.
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    PublicationOpen Access
    Melatonin is more effective than ascorbic acid and β-carotene in improvement of gastric mucosal damage induced by intensive stress.
    (2015-10-12) AKINCI, A; Esrefoglu, MUKADDES; CETIN, A; ATES, B; EŞREFOĞLU, MUKADDES
    Introduction: Oxidative stress has been considered to play a primary role in the pathogenesis of stress-induced gastric damage. The aim of this study was to investigate the effects of melatonin, ascorbic acid and β-carotene on stress-induced gastric mucosal damage. Material and methods: Fifty-six male Wistar albino rats were divided into control, stress, stress + standard diet, stress + saline, stress + melatonin, stress + ascorbic acid and stress + β-carotene groups. The rats from stress groups were exposed to starvation, immobilization and cold by immobilizing for 8 h at +4°C following 72-hour food restriction. Following stress application, melatonin, ascorbic acid and β-carotene were administered for 7 days. Specimens of gastric tissue were prepared for microscopic and biochemical examinations. Results: Mean histopathological damage scores and mean tissue malondialdehyde levels were significantly decreased but mean tissue glutathione levels and glutathione peroxidase and superoxide dismutase activities were increased in treatment groups vs. stress groups in general. Mean histopathological damage scores of the stress + Mel group was lower than those of stress + D, stress + S, stress + β-car (p < 0.05) and stress + Asc groups (p < 0.005). Additionally, mean tissue catalase activity of the stress + Mel group was higher than that of stress + S (p < 0.005), stress + D (p < 0.05) and stress + β-car groups (p < 0.05). Conclusions: Melatonin is more effective than ascorbic acid and β-carotene in improvement of gastric damage induced by intensive stress. We suggest that as well as the direct antioxidant and free radical scavenging potency of melatonin, its indirect effect via the brain-gut axis might account for its greater beneficial action against stress-induced gastric damage.
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    PublicationOpen Access
    Oxidative stress and benefits of antioxidant agents in acute and chronic hepatitis.
    (2012-03-01) Esrefoglu, MUKADDES; EŞREFOĞLU, MUKADDES
    Context: Oxidative damage due to oxidative stress is the failure of the cell’s defense against the deleterious effects of harmful agents by means of its numerous autoprotective mechanisms. Oxidative stress is a key impairment induced by various conditions, including atherosclerosis, hypertension, ischemia-reperfusion, hepatitis, pancreatitis, cancer, and neurodegenerative diseases. Evidence Acquisition: Oxidative stress is a common pathogenetic mechanism contributing to the initiation and progression of hepatic damage in cases of inflammatory liver disorders, including acute and chronic hepatitis. Antioxidant administration is a good therapeutic strategy for the treatment of hepatitis. Results: Our comprehensive review of the literature revealed that contradictory results have been obtained with many antioxidants and antioxidant agents. Conclusion: Since clinical studies to date have generally involved testing of the effects of antioxidant mixtures containing more than 2 antioxidants and also have been limited because of toxic effects of high doses of some antioxidants, antioxidant therapy for acute and chronic hepatitis needs further study.
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    PublicationOpen Access
    Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage.
    (2017-01-01) AKıNCı, Ayşin; Eşrefoğlu, MUKADDES; TASLIDERE, ELİF; ATES, B; EŞREFOĞLU, MUKADDES; TAŞLIDERE, ELİF
    Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum) contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study design: Animal experimentation. Methods: Forty male Wistar albino rats were divided into five groups: control, stress, stress + standard diet, stress + parsley-added diet and stress + lansoprazole (LPZ) groups. Subjects were exposed to 72 hours of fasting and later immobilized and exposed to the cold at +4 degrees for 8 hours to create a severe stress condition. Samples from the animals' stomachs were arranged for microscopic and biochemical examinations. Results: Gastric mucosal injury was obvious in rats exposed to stress. The histopathologic damage score of the stress group (7.00±0.57) was higher than that of the control group (1.50±0.22) (p<0.05). Significant differences in histopathologic damage score were found between the stress and stress + parsley-added diet groups (p<0.05), the stress and stress + standard diet groups (p<0.05), and the stress and stress + LPZ groups (p<0.05). The mean tissue malondialdehyde levels of the stress + parsley-added group and the stress + LPZ group were lower than that of the stress group (p<0.05). Parsley supported the cellular antioxidant system by increasing the mean tissue glutathione level (53.31±9.50) and superoxide dismutase (15.18±1.05) and catalase (16.68±2.29) activities. Conclusion: Oral administration of parsley is effective in reducing stress-induced gastric injury by supporting the cellular antioxidant defence system.