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Öğe 8 Melatonin, quercetin and resveratrol attenuates oxidative hepatocellular injury in streptozotocin-induced diabetic rats(Sage Publications Ltd, 2015) Elbe, H.; Esrefoglu, M.; Vardi, N.; Taslidere, E.; Ozerol, E.; Tanbek, K.In this study, effects of melatonin, quercetin and resveratrol on hepatocellular injury in streptozotocin (STZ)-induced experimental diabetes were aimed to be investigated by histological and biochemical methods. Thirty-five male Wistar albino rats were divided into five groups, namely, control, diabetes (STZ 45 mg/kg/single dose/intraperitoneally (ip)), diabetes + melatonin (10 mg/kg/30 days/ip), diabetes + quercetin (25 mg/kg/30 days/ip) and diabetes + resveratrol (10 mg/kg/30 days/ip). Initial and final blood glucose levels and body weights (BWs) were measured. At the end of the experimentation, following routine tissue processing procedure, sections were stained with haematoxylin-eosin (H-E), periodic acid Schiff and Masson's trichrome. Tissue malondialdehyde (MDA) and glutathione (GSH) levels and superoxide dismutase (SOD) and catalase (CAT) activities were examined. The diabetic rats had significantly higher blood glucose levels than those of control rats (p = 0.0001). Mean BWs of diabetic rats were significantly decreased when compared with the control rats (p = 0.0013). Histopathological alterations including cellular glycogen depletion, congestion, sinusoidal dilatation, inflammation and fibrosis were detected in diabetes group. On the other hand, histopathological changes markedly reduced in all of the treatment groups (p = 0.001). Mean tissue MDA level was increased but mean tissue CAT and SOD activities and GSH levels were decreased in the diabetes group. Melatonin, quercetin and resveratrol administered diabetic rats showed an increase in CAT activities and GSH levels and a decrease in MDA levels (p < 0.05, for all). Melatonin, quercetin and resveratrol administrations markedly reduced hepatocellular injury in STZ-induced experimental diabetes.Öğe Adrenomedullin Reduces Antioxidant Defense System and Enhances Kidney Tissue Damage in Cadmium and Lead Exposed Rats(Wiley, 2009) Yurekli, Muhittin; Esrefoglu, M.; Dogru, M. Ilker; Dogru, Arzu; Gul, M.; Whidden, M.Adrenomedullin (AdM) is synthesized and secreted by a number of cells and tissue. AdM is a potent vasodilator but it is also considered a neuromodulator, an angiogenic factor, and a hormone regulator. AdM possess antiapoptotic, antioxidant, and antimicrobial properties. Heavy metals such as cadmium and lead are found widely in the environment and they have important biological functions. Lead (Pb) and cadmium (Cd) can accumulate in the lungs, liver, bone, and kidneys and cause serious organ damage. In the present study, we investigated the effect of AdM, Pb + AdM, and Cd + AdM treatments on superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities as well as the level of malondialdehyde (MDA) in the kidney. Heavy metal accumulation was determined in kidney with and without AdM infusion and kidney damage was evaluated by light and electron microscopy. Increased heavy metal accumulation was observed in the heavy metal and AdM treated groups. SOD, CAT, GSH-Px activities, and MDA levels were significantly different in the treatment groups when compared with the control group. Tubular degeneration, necrosis, cell swelling, mononuclear cell infiltration, and degenerated organelles were observed in the kidney following treatment. Therefore, AdM infusion has no beneficial and/or compensatory role in cadmium and lead toxicity in the kidney. We conclude that heavy metal accumulation in the kidney in conjunction with AdM infusion is cytotoxic despite the known beneficial effects of adrenomedullin. (C) 2008 Wiley Periodicals, Inc. Environ Toxicol 24: 279-286, 2009.Öğe Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats(Sage Publications Ltd, 2015) Elbe, H.; Vardi, N.; Esrefoglu, M.; Ates, B.; Yologlu, S.; Taskapan, C.The role of oxygen radicals are known for the pathogenesis of kidney damage. The aim of the present study was to investigate the antioxidative effects of melatonin, quercetin, and resveratrol on streptozotocin (STZ)-induced diabetic nephropathy in rats. A total of 35 male Wistar rats were divided into 5 groups as follows: control, diabetes mellitus (DM), DM + melatonin, DM + quercetin, and DM + resveratrol. All the injections started on the same day of single-dose STZ injection and continued for 30 days. At the end of this period, kidneys were removed and processed for routine histological procedures. Biochemical parameters and morphological changes were examined. In DM group, blood glucose levels were significantly increased, whereas body weights were decreased compared with the control group. Significant increases in blood urea nitrogen and tissue malondialdehyde (MDA) levels and decreases in superoxide dismutase and catalase activities were detected in DM group. Administration of melatonin, quercetin, and resveratrol significantly reduced these values. Melatonin was more efficient in reducing MDA levels than other antioxidants (p < 0.05). STZ-induced histopathological alterations including epithelial desquamation, swelling, intracytoplasmic vacuolization, brush border loss and peritubular infiltration. Additionally, basement membrane thickening and sclerotic changes were observed in glomerulus. Transforming growth factor-1 positive cells were also increased. Melatonin, quercetin, and resveratrol significantly reduced these histopathological changes. Our results indicate that melatonin, quercetin, and resveratrol might be helpful in reducing diabetes-induced renal damageÖğe Ascorbic acid and beta-carotene reduce stress-induced oxidative organ damage in rats(Taylor & Francis Inc, 2016) Esrefoglu, M.; Akinci, A.; Taslidere, E.; Elbe, H.; Cetin, A.; Ates, B.Antioxidants are potential therapeutic agents for reducing stress-induced organ damage. We investigated the effects of ascorbic acid and -carotene on oxidative stress-induced cerebral, cerebellar, cardiac and hepatic damage using microscopy and biochemistry. Male Wistar albino rats were divided into five groups: untreated control, stressed, stressed + saline, stressed + ascorbic acid and stressed + -carotene. The rats in the stressed groups were subjected to starvation, immobilization and cold. The histopathological damage scores for the stressed and stressed + saline groups were higher than those of the control group for all organs examined. The histopathological damage scores and mean tissue malondialdehyde levels for the groups treated with antioxidants were lower than those for the stressed and stressed + saline groups. Mean tissue superoxide dismutase activities for groups that received antioxidants were higher than those for the stressed + saline group for most organs evaluated. Ascorbic acid and -carotene can reduce stress-induced organ damage by both inhibiting lipid oxidation and supporting the cellular antioxidant defense system.Öğe Congenital Cutis Laxa Associated with Growth Retardation(Univ West Indies Faculty Medical Sciences, 2008) Seyhan, M.; Esrefoglu, M.; Ozcan, H.; Akinci, A.Congenital cutis laxa is a rare, clinically and,genetically heterogeneous group of inherited disorders. It is characterized by degenerative changes in elastic fibres and manifests with skin laxity. Here we presented a six-month old boy with congenital cutis laxa associated with growth retardation. We reveal ultrastructural findings and discussed the differential diagnosis.Öğe Effects of melatonin and acetylsalicylic acid against hepatic oxidative stress after bile duct ligation in rat(Akademiai Kiado Zrt, 2008) Emre, M. H.; Polat, A.; Esrefoglu, M.; Karabulut, A. B.; Gul, M.The aim of this study was to assess the effect of melatonin and acetylsalicylic acid (ASA) on hepatic damage induced by bile duct ligation (BDL) Material and methods: Male Sprague-Dawley rats were subjected to either sham operation or common BDL before treatment with ASA, melatonin or vehicle. Hepatic superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) enzyme activities and reduced glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) levels were evaluated. Results: Our results have indicated that BDL caused a significant increase in lipid peroxidation whereas a statistically insignificant decrease in GSH level and some of the antioxidant enzyme activities. Both MEL and ASA administrations, either separately or together, decreased MDA whereas co-administration of MEL with ASA increased GSH levels in BDL rats. Conclusions: CAT activity and MEL level decreased in the liver tissues of rats with BDL after administration of either melatonin alone or with ASA. However, melatonin and ASA administration increases liver tissue GSH levels in BDL ligated ratsÖğe Effects of melatonin on both testicular regeneration and recovery of spermatogenesis in busulfan-treated rats(Univ Sao Paulo, Conjunto Quimicas, 2022) Taslidere, E.; Esrefoglu, M.; Tok, O. E.; Taslidere, B.; Bulut, H.Testicular damage is one of the most hazardous effects of chemotherapy as it is frequently associated with oligozoospermia and azoospermia. This study aimed at evaluating the protective effect of melatonin in a rat model of busulfan-induced testicular injury. Rats were divided into four groups: control, melatonin, busulfan, busulfan plus melatonin. After 15 days, the semen was collected from the epididymis and testes were assessed. Sperm removed from cauda epididymis and analyzed for sperm count and viability. Testis tissues were also removed, fixed in formalin and were embedded in paraffin. Sections of testis tissue were stained with hematoxylin-eosin for histological examination and prepared for TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) assay to detect apoptosis and PCNA (proliferating cell nuclear antigenassay) to detect proliferation cells. Serum and testes supernatants were separated to detect testosteron level and oxidative stress parameters. In histological examination, degenerative changes in seminiferous tubules were observed in the experimental groups. In biochemical examination, the total oxidant status (TOS) levels in Busulfan group were significantly higher than in the control group while the total antioxidant status (TAS) levels of all the groups were similar. In conclusion, the beneficial properties of melatonin treatment by its potent anti-oxidants may reduce adverse effects of chemotherapy in the reproductive system in a rodent system.Öğe The effects of pentoxifylline and caffeic acid phenethyl ester in the treatment of d-galactosamine-induced acute hepatitis in rats(Sage Publications Ltd, 2016) Taslidere, E.; Vardi, N.; Esrefoglu, M.; Ates, B.; Taskapan, C.; Yologlu, S.The aim of this study was to investigate histological changes in hepatic tissue and effects of pentoxifylline (PTX) and caffeic acid phenethyl ester (CAPE) on these changes using histochemical and biochemical methods in rats, in which hepatitis was established by d-galactosamine (d-GAL). Rats were divided into five groups as follows: control group, d-GAL (24 h) group, d-GAL group, d-GAL + PTX group, and d-GAL + CAPE group. In histological evaluations, the control group showed normal appearance of the liver cells. However in the d-GAL groups, focal areas consisting of inflammatory, necrotic, and apoptotic cells were detected in parenchyma. Glycogen loss was observed in the hepatocytes localized at the periphery of lobule. It was found that number of mast cells of portal areas were significantly higher in d-GAL groups compared with other groups (p = 0.0001). In addition, the number of cells with positive staining by Ki-67 and caspase-3 were significantly increased in GAL groups compared with the control group (p = 0.0001). In biochemical analysis, there was an increase in malondialdehyde and myeloperoxidase levels, while a decrease was observed in glutathione level and glutathione peroxidase activity in groups treated with d-GAL compared with the control group. On the other hand, it was seen that, in the groups treated with d-GAL, histological and biochemical injuries in the liver were reduced by administration of PTX and CAPE. In this study, we demonstrated the ameliorative effects of PTX and CAPE on d-GAL-induced liver injury.Öğe Liver lipid peroxidation and antioxidant capacity in cerulein-induced acute pancreatitis(Assoc Bras Divulg Cientifica, 2009) Batcioglu, K.; Gul, M.; Uyumlu, A. B.; Esrefoglu, M.The aim of this study was to evaluate the role of oxidative damage in pancreatitis-induced hepatic injury. Thirty-five rats were divided into five groups (each of 7 rats): control, cerulein (100 mu g/kg body weight), cerulein and pentoxifylline (12 mg/kg body weight), cerulein plus L-NAME (10 mg/kg body weight) and cerulein plus L-arginine (160 mg/kg body weight). The degree of hepatic cell degeneration differed significantly between groups. Mean malondialdehyde levels were 7.00 +/- 2.29, 20.89 +/- 10.13, 11.52 +/- 4.60, 18.69 +/- 8.56, and 8.58 +/- 3.68 nmol/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Mean catalase activity was 3.20 +/- 0.83, 1.09 +/- 0.35, 2.05 +/- 0.91, 1.70 +/- 0.60, and 2.85 +/- 0.47 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively, and mean glutathione peroxidase activity was 0.72 +/- 0.25, 0.33 +/- 0.09, 0.37 +/- 0.04, 0.34 +/- 0.07 and 0.42 +/- 0.1 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Cerulein-induced liver damage was accompanied by a significant increase in tissue malondialdehyde levels (P < 0.05) and a significant decrease in catalase (P < 0.05) and GPx activities (P < 0.05). L-arginine and pentoxifylline, but not L-NAME, protected against this damage. Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage.Öğe The protective effect of melatonin in lungs of newborn rats exposed to maternal nicotine(Taylor & Francis Ltd, 2018) Yildiz, A.; Vardi, N.; Karaaslan, M. G.; Ates, B.; Taslidere, E.; Esrefoglu, M.We investigated possible healing effects of melatonin (MEL) on biochemical and histological changes in the lungs of rat offspring caused by exposure to nicotine (NT) in utero. Pregnant rats were divided randomly into five groups. The SP group was treated with physiological saline. The EA group was treated with ethyl alcohol. The MEL group was treated with MEL. The NT group was treated with NT. The NT + MEL group was treated with NT and MEL. At the end of the study, the biochemistry and histopathology of lung tissue of the offspring were examined. Reduced alveolar development and increased numbers of alveolar macrophages and mast cells were observed in the NT group compared to the SP, EA and MEL groups. We also found increased malondialdehyde (MDA) levels and decreased total glutathione (GSH) levels in the NT group. Application of MEL ameliorated the histological and biochemical damage caused by NT. The number of alveoli was greater in the NT + MEL group than in the NT group. Also, the increased numbers of alveolar macrophages and mast cells resulting from exposure to NT were decreased following MEL treatment. We found that MEL caused a significant decrease in the level of MDA. Maternal exposure to NT caused significant structural and biochemical changes in the lungs of the offspring and administration of MEL ameliorated the changes.Öğe Therapeutic effects of melatonin and quercetin in improvement of hepatic steatosis in rats through supression of oxidative damage(Comenius Univ, 2017) Esrefoglu, M.; Cetin, A.; Taslidere, E.; Elbe, H.; Ates, B.; Tok, O. E.; Aydin, M. S.BACKGROUND: Non-alcoholic steatohepatitis, a cause of cirrhosis, is characterized by fatty infiltration of the liver, inflammation, hepatocellular damage and fibrosis. The aim of the present study was to investigate the effects of melatonin and quercetin on CCl4-induced steatosis characterized by fatty infiltration of the liver, inflammation, hepatocellular damage and fibrosis. METHODS: Rats were divided into 5 groups: Ethanol, Olive oil, CCl4, CCl4+Melatonin (CCl4+Mel), CCl4+Quercetin. Rats were sacrificed and livers were removed for being evaluated by histopathological, immunohistochemical and biochemical methods. RESULTS: In CCl4 group, vacuolization, vascular congestion, haemorrhage, necrosis, and inflammatory infiltration were identified. The mean tissue MDA level was increased, whereas GSH level and SOD and CAT activities were decreased in comparison with ethanol and olive oil groups. MDA levels were decreased in CCl4+Quercetin and CCl4+Mel groups versus CCl4 group. CAT activity of CCl4+Mel group was higher than that of CCl4 and CCl4+Quercetin groups. The mean tissue GSH level of CCl4+Mel group versus CCl4 group was significantly increased. CONCLUSIONS: By the means of histopathological examination, we suggest that both agents are beneficial against necrotic and apoptotic cell death during steatosis. Thus, melatonin and quercetin might be beneficial in the improvement of hepatic steatosis by supporting conventional therapy in humans (Tab. 1, Fig. 5, Ref. 53). 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