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1. Not only melatonin but also caffeic acid phenethyl ester protects kidneys against aging-related oxidative damage in Sprague Dawley rats.

Author

Eşrefoğlu M, Iraz M, Ateş B, and Gül M

Subjects
Animals, Antioxidants therapeutic use, Kidney metabolism, Male, Phenylethyl Alcohol pharmacology, Rats, Rats, Sprague-Dawley, Aging, Caffeic Acids pharmacology, Cytoprotection, Kidney drug effects, Melatonin pharmacology, Oxidative Stress drug effects, Phenylethyl Alcohol analogs & derivatives
Abstract

Microscopic features and antioxidant status of kidneys of young, old, and caffeic acid phenethyl ester (CAPE) and melatonin administered old Sprague Dawley rats were evaluated. Aging-related tubular and glomerular changes were evident. The most prominent tubular alterations were massive vacuole formation, mitochondrial degeneration, and lysosome accumulation. Mean tissue malondialdehyde (MDA) level was increased, mean tissue superoxide dismutase (SOD), catalase (CAT) (p < .001), and glutathione peroxidase (GPx) activities (p < .05), and total glutathione (GSH) level were decreased in old animals. Melatonin significantly reduced tissue MDA levels (p < .005), but increased tissue SOD (p < .001), CAT, and GPx activities (p < .05), and GSH levels (p < .005) in old animals. CAPE also significantly reduced tissue MDA levels (p < .005), but increased tissue SOD (p < .05), CAT (p < .005), GPx activities, and GSH levels (p < .001) in old rats. Mean tissue MDA levels of melatonin and CAPE-administered rats were even lower than those of young rats (p < .05). In conclusion, tubular and glomerular structures and tissue antioxidant enzyme activities were very well preserved in CAPE and melatonin-administered rats.

Published
2012
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2. The effects of caffeic acid phenethyl ester and melatonin on age-related vascular remodeling and cardiac damage.

Author

Eşrefoğlu M, Gül M, Ateş B, and Erdoğan A

Subjects
Animals, Antioxidants metabolism, Aorta physiopathology, Aorta ultrastructure, Catalase metabolism, Disease Models, Animal, Drug Evaluation, Preclinical, Enzyme Assays, Glutathione analysis, Glutathione metabolism, Heart physiopathology, Lipid Peroxidation, Male, Malondialdehyde metabolism, Melatonin metabolism, Mitochondria pathology, Mitochondria ultrastructure, Myocardium metabolism, Myocardium pathology, Myocardium ultrastructure, Oxidative Stress, Phenylethyl Alcohol pharmacology, Rats, Rats, Sprague-Dawley, Superoxide Dismutase metabolism, Aging physiology, Antioxidants pharmacology, Caffeic Acids pharmacology, Heart drug effects, Melatonin pharmacology, NF-kappa B antagonists & inhibitors, Phenylethyl Alcohol analogs & derivatives
Abstract

Oxidative stress has been implicated with cardiovascular aging. Most antioxidant intervention studies have involved long-term treatments as a potential means to eliminate age-related oxidative damage in many systems. In the present study, not only light and electron microscopic pictures of the heart and thoracic aorta of young and aged and, caffeic acid phenethyl ester (CAPE) and melatonin and administered aged Sprague Dawley rats, but also antioxidant system status was evaluated. Significantly elevated levels of malondialdehyde (MDA) were observed in the heart and thoracic aorta of aged rats (P<0.05 and P<0.001, respectively). Chronic melatonin and CAPE administration significantly reduced the levels of MDA in the heart (P=0.005 and P=0.05, respectively) and thoracic aorta (P<0.001 and P<0.05, respectively) of aged animals. Additionally, melatonin and CAPE were efficient in stimulating the activities and increasing the levels of the antioxidant enzymes in the heart and aorta. Prominent electron microscopic alterations in cardiac myocytes such as nuclear irregularity, mitochondrial degeneration, myofilament disorganization and disruption, and lipofuscin accumulation were observed in aged rats. The main age-related histologic modifications observed in aorta were irregularity in endothelial cells and their nuclei, divergence of endothelial cells from basement membrane and neighboring cells, and elastic fibril fragmentation and reduction. Melatonin and CAPE obviously reduced these alterations in both heart and aorta of aged rats. Taking the results together, we suggest that supplemental administration of CAPE and melatonin is beneficial in delaying age-related cellular damage in cardiovascular system., (© 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.)

Published
2011
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3. The ultrastructural and biochemical evidences of the beneficial effects of chronic caffeic acid phenethyl ester and melatonin administration on brain and cerebellum of aged rats.

Author

Eşrefoğlu M, Gül M, Ateş B, and Yilmaz I

Subjects
Aging pathology, Animals, Brain drug effects, Brain pathology, Caffeic Acids therapeutic use, Cerebellum pathology, Cerebellum ultrastructure, Cerebrum drug effects, Cerebrum pathology, Cerebrum ultrastructure, Drug Administration Schedule, Male, Melatonin therapeutic use, Neurons drug effects, Neurons pathology, Neurons ultrastructure, Phenylethyl Alcohol administration & dosage, Phenylethyl Alcohol therapeutic use, Rats, Rats, Sprague-Dawley, Aging drug effects, Brain ultrastructure, Caffeic Acids administration & dosage, Cerebellum drug effects, Melatonin administration & dosage, Phenylethyl Alcohol analogs & derivatives
Abstract

Nervous system is highly vulnerable to the deleterious effects of age-related oxidative stress. A large body of researches has consistently confirmed the implication of free radicals both in normal cerebral ageing and ageing-related pathologies. In the present study, in addition to the light and electron microscopic pictures of brain and cerebellum of young, old and antioxidant administered old Sprague-Dawley rats, pro-oxidant status was evaluated in terms of measurements of total glutathione, lipid peroxidation (malondialdehyde) and activities of superoxide dismutase, catalase and glutathione peroxidase. Taking the results together, we suggest that supplemental administration of caffeic acid phenethyl ester and melatonin is beneficial in delaying age-related cellular damage in nervous system.

Published
2010
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4. Protective effects of melatonin and aminoguanidine on the cornea in streptozotocin-induced diabetic rats.

Author

Gül M, Emre S, Eşrefoğlu M, and Vard N

Subjects
Administration, Oral, Animals, Blood Glucose analysis, Body Weight, Corneal Diseases etiology, Corneal Diseases pathology, Diabetes Mellitus, Experimental etiology, Diabetes Mellitus, Experimental pathology, Female, Injections, Intraperitoneal, Nitric Oxide Synthase antagonists & inhibitors, Rats, Rats, Sprague-Dawley, Antioxidants administration & dosage, Corneal Diseases prevention & control, Diabetes Mellitus, Experimental prevention & control, Enzyme Inhibitors administration & dosage, Guanidines administration & dosage, Melatonin administration & dosage
Abstract

Purpose: This study was designed to investigate the protective effect of aminoguanidine (AG) and melatonin (M) on the cornea in a streptozotocin-induced diabetic rat model., Methods: Twenty-eight Sprague-Dawley rats were used in this study. Animals were divided into 4 groups: control (C), diabetes (D), diabetes + AG (D+AG), and diabetes + M (D+M). Diabetes was induced by 1 intraperitoneal dose of 45 mg/kg of streptozotocin (STZ). In the treatment groups, the D + AG group received AG in their water (1 g/L), and D + M rats were injected with M (10 mg/kg/d) intraperitoneally. One of the groups remained an untreated diabetic group (D group). All animals were euthanized at the end of 8 weeks. After enucleation, eyes were fixed in 10% phosphate-buffered formalin and embedded in paraffin wax. Histochemical stains were applied, and specimens were examined under a light microscope., Results: After 8 weeks, the rats in the diabetes group had significantly lower body weight and significantly higher blood glucose levels than those of the control, D + AG, and D + M groups. Diabetes resulted in prominent edema in the stroma with interruptions in the subepithelial basement membrane. These alterations were not prominent or were absent in the D + AG and D + M groups. The mean thicknesses of the cornea, corneal epithelium, and stroma were statistically significantly different between the C and D, and D and D + AG and D + M groups (P < 0.05)., Conclusions: Long-term administration of AG and M reduced corneal injury in an STZ-induced diabetic rat model. AG and M may be potential candidates in the treatment of diabetic keratopathies. However, further studies are needed to elucidate the mechanisms of the protective effect of both molecules on diabetic corneal complications.

Published
2008
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5. Ultrastructural clues for the potent therapeutic effect of melatonin on aging skin in pinealectomized rats.

Author

Eşrefoğlu M, Gül M, Seyhan M, and Parlakpinar H

Subjects
Animals, Male, Melatonin therapeutic use, Mitochondria ultrastructure, Pineal Gland surgery, Rats, Rats, Wistar, Skin drug effects, Melatonin pharmacology, Pineal Gland physiology, Skin ultrastructure, Skin Aging drug effects, Skin Aging pathology
Abstract

Recently we have reported a significant reduction in the thickness of epidermis and epidermis + dermis in the back, abdominal and thoracic skin of the long-term pinealectomized rats and the potent therapeutic effect of melatonin on the pinealectomy-induced morphometric changes. The present study was aimed to determine the fine structure of the abdominal and thoracic skin in pinealectomized rats and the effect of melatonin on skin ultrastructure. Rats were pinealectomized or sham operated (control) for 6 months. Half of the pinealectomized rats were treated with 4 mg/kg melatonin during the last month of the experiment. Pinealectomy resulted in prominent ultrastructural changes in the skin. Epidermal atrophy, disorganization and cytological atypia were obvious. Tonofilament distribution was not uniform, and intercellular space was narrow. Nuclear irregularity and heterochromatin condensation were detected. Many mitochondria were irregular and edematous with increased translucence of the matrix, either partial or total destruction of crests and frequently the presence of vacuoles, myelin figures and dense bodies. Microprojections of basal cells into the dermis were observed. The dermis was thin, and collagenous fibers were loosely arranged. The epidermis in melatonin administered pinealectomized rats was obviously thicker than that of pinealectomized rats. The cells of each layers had characteristic morphological and ultrastructural features. Nuclear irregularity and heterochromatin condensation were not seen. Mitochondria were generally normal in ultrastructural appearance but rarely vacuoles and myelin figures were observed. The dermis was thick, and collagenous fibers were closely packaged. This paper provides an additional ultrastructural evidence that the damage to mitochondria is the major contributory factor to skin aging and that melatonin has potent therapeutic effects in reducing age-related changes via protecting fine structure of the skin.

Published
2006
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6. Antioxidative effect of melatonin, ascorbic acid and N-acetylcysteine on caerulein-induced pancreatitis and associated liver injury in rats.

Author

Eşrefoğlu M, Gül M, Ates B, Batçioğlu K, and Selimoğlu MA

Subjects
Acute Disease, Animals, Female, Lipid Peroxidation drug effects, Liver drug effects, Pancreatitis chemically induced, Pancreatitis metabolism, Pancreatitis pathology, Rats, Rats, Wistar, Reactive Oxygen Species, Acetylcysteine pharmacology, Antioxidants pharmacology, Ascorbic Acid pharmacology, Ceruletide toxicity, Liver pathology, Melatonin pharmacology, Pancreatitis drug therapy
Abstract

Aim: To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis and associated liver injury in rats., Methods: Thirty-eight female Wistar rats were used. Acute pancreatitis (AP) was induced by two i.p. injections of caerulein at 2-h intervals (at a total dose of 100 microg/kg b.wt). The other two groups received additional melatonin (20 mg/kg b.wt) or an antioxidant mixture containing L(+)-ascorbic acid (14.3 mg/kb.wt.) and N-acetyl cysteine (181 mg/kg b.wt.) i.p. shortly before each injection of caerulein. The rats were sacrificed by decapitation 12 h after the last injection of caerulein. Pancreatic and hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde (MDA) and changes in tissue antioxidant enzyme levels, catalase (CAT) and glutathione peroxidase (GPx). Histopathological examination was performed using scoring systems., Results: The degree of hepatic cell degeneration, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration showed a significant difference between caerulein and caerulein + melatonin (P = 0.001), and careulein and caerulein + L(+)-ascorbic acid + N-acetyl cysteine groups (P = 0.002). The degree of aciner cell degeneration, pancreatic edema, intracellular vacuolization and inflammatory infiltration showed a significant difference between caerulein and caerulein + melatonin (P = 0.004), and careulein and caerulein + L(+)-ascorbic acid + N-acetyl cysteine groups (P = 0.002). Caerulein-induced pancreatic and liver damage was accompanied with a significant increase in tissue MDA levels (P = 0.01, P = 0.003, respectively) whereas a significant decrease in CAT (P = 0.002, P = 0.003, respectively) and GPx activities (P = 0.002, P = 0.03, respectively). Melatonin and L(+)-ascorbic acid+N-acetyl cysteine administration significantly decreased MDA levels in pancreas (P=0.03, P=0.002, respectively) and liver (P = 0.007, P = 0.01, respectively). Administration of these agents increased pancreatic and hepatic CAT and GPx activities. Melatonin significantly increased pancreatic and hepatic CAT (P = 0.002, P = 0.001, respectively) and GPx activities (P = 0.002, P = 0.001). Additionally, L(+)-ascorbic acid + N-acetyl cysteine significantly increased pancreatic GPx (P = 0.002) and hepatic CAT and GPx activities (P = 0.001, P = 0.007, respectively)., Conclusion: Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage. Antioxidant agents such as melatonin and ascorbic acid + N-acetyl cysteine, are capable of limiting pancreatic and hepatic damage produced during AP via restoring tissue antioxidant enzyme activities.

Published
2006
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7. Ultrastructural clues for the protective effect of melatonin against oxidative damage in cerulein-induced pancreatitis.

Author

Eşrefoğlu M, Gül M, Ateş B, and Selimoğlu MA

Subjects
Acute Disease, Animals, Apoptosis, Autophagy, Catalase metabolism, Ceruletide, Female, Glutathione metabolism, Glutathione Peroxidase metabolism, Lipid Peroxidation, Microscopy, Electron, Pancreas metabolism, Pancreatitis chemically induced, Phagosomes ultrastructure, Rats, Rats, Sprague-Dawley, Superoxide Dismutase metabolism, Melatonin pharmacology, Oxidative Stress drug effects, Pancreas ultrastructure, Pancreatitis drug therapy, Pancreatitis physiopathology
Abstract

The role of oxidative stress has been evaluated in experimental models of acute pancreatitis (AP). The aim of this study is to investigate the effect of melatonin on the ultrastructural changes in cerulein-induced AP in rats. Acute pancreatitis was induced by two i.p. injections of cerulein at 2-hr intervals (50 microg/kg BW). One group received additionally melatonin (20 mg/kg BW) i.p. before each injection of cerulein. The rats were sacrificed 12 hr after the last injection. Pancreatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides and changes in the antioxidant enzyme levels, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total glutathione (GSH) levels. Ultrastructural examination was performed using a transmission electron microscope. Formation of numerous, large autophagosomes, mitochondrial damage, dilatation of rough endoplasmic reticulum (RER) and Golgi apparatus, margination and clumping of nuclear chromatin were the major ultrastructural alterations observed in the AP group. Melatonin administration prevented mitochondrial and nuclear changes and dilatation of RER and Golgi apparatus. Rare, small autophagosomes were present within the cytoplasm of some of the acinar cells. Pancreatic damage was accompanied by a significant increase in tissue MDA levels (P < 0.05) and a significant decrease in CAT, SOD, GPx activities and GSH levels (P < 0.005). Melatonin administration significantly reduced MDA levels but increased CAT, SOD, GPx activities and GSH levels (P < 0.005). Melatonin also reduced serum amylase and lipase activities, which were significantly elevated in AP (P < 0.05 and P < 0.005 respectively). These results suggest that oxidative injury is important in the pathogenesis of AP. Melatonin is potentially capable of limiting pancreatic damage produced during AP by protecting the fine structure of acinar cells and tissue antioxidant enzyme activities.

Published
2006
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8. Potent therapeutic effect of melatonin on aging skin in pinealectomized rats.

Author

Eşrefoğlu M, Seyhan M, Gül M, Parlakpinar H, Batçioğlu K, and Uyumlu B

Subjects
Aging physiology, Animals, Catalase metabolism, Glutathione Peroxidase metabolism, Male, Malondialdehyde metabolism, Oxidative Stress drug effects, Rats, Rats, Wistar, Skin enzymology, Skin metabolism, Aging drug effects, Melatonin therapeutic use, Pineal Gland physiology, Skin drug effects, Skin Physiological Phenomena drug effects
Abstract

It is generally agreed that one of the major contributors to skin aging is reactive oxygen species. As organisms reach advanced age, free radical generation increases and the activity of tissue antioxidant enzyme system decreases. Melatonin is an antioxidant and free radical scavenger. The present study was first aimed to determine the morphometric and biochemical changes caused by long-term pinealectomy in order to investigate the role of melatonin as skin architecture. Secondly, the effect of exogenous melatonin administration on these changes was determined. Rats were pinealectomized or sham operated (control) for 6 months. Half of the pinealectomized rats were treated with 4 mg/kg melatonin during the last month of the experiment. Pinealectomy resulted in important morphometric and biochemical changes in the back, abdominal and thoracic skin. The thickness of epidermis and dermis and the number of dermal papillae and hair follicles were reduced. Melatonin administration to pinealectomized rats significantly improved these alterations in all body areas (P < 0.005). On the contrary, in pinealectomized rats the levels of antioxidant enzymes, catalase and glutathione peroxidase were decreased. Melatonin restored the levels of these enzymes. The pinealectomy-induced increases in lipid peroxidation in the abdominal and thoracic skin were significantly reduced by melatonin treatment (P < 0.005 and 0.01 respectively). These results suggest that melatonin is highly efficient anti-aging factor and, as melatonin levels decrease with age, melatonin treatment may reduce age-related skin changes.

Published
2005
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9. Effects of melatonin and caffeic acid phenethyl ester on testicular injury induced by myocardial ischemia/reperfusion in rats.

Author

Eşrefoğlu M, Gül M, Parlakpinar H, and Acet A

Subjects
Animals, Atrophy, Blood Pressure drug effects, Free Radicals metabolism, Male, Malondialdehyde metabolism, Myocardial Reperfusion Injury pathology, Myocardium pathology, Nitric Oxide metabolism, Oxidative Stress drug effects, Rats, Rats, Wistar, Testicular Diseases pathology, Testis pathology, Antioxidants pharmacology, Caffeic Acids pharmacology, Melatonin pharmacology, Myocardial Reperfusion Injury complications, Phenylethyl Alcohol analogs & derivatives, Phenylethyl Alcohol pharmacology, Testicular Diseases etiology, Testicular Diseases prevention & control
Abstract

Experimental studies indicate that ischemia/reperfusion (I/R) causes remote organ injury although the molecular mechanism has not been clearly defined. In this report, the role of oxidative injury on testicular damage following myocardial I/R injury and the effects of antioxidant agents, melatonin and caffeic acid phenethyl ester (CAPE), on testicular injury were investigated. As far as we know, this is the first report demonstrating that myocardial I/R induces damage to the testes. Thirty-two male Wistar rats were randomly divided into four groups: sham operation (SO), I/R + vehicle, I/R + melatonin, and I/R + caffeic acid phenethyl ester. To produce cardiac damage, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Serum nitric oxide (NO) and malondialdehyde (MDA) levels and morphological changes were examined. I/R was accompanied by a significant increase in serum MDA and NO levels, whereas, melatonin and CAPE administration significantly reduced these values. Melatonin was more efficient in reducing MDA levels than CAPE (P < 0.05). I/R induced myocardial damage, manifested as the histopathological evidence of intracellular vacuolization, interstitial edema, neutrophil infiltration and coagulative necrosis. I/R + vehicle group showed many histological alterations such as focal tubular atrophy, and degeneration and disorganization of the seminiferous epithelium in testes. The number of atrophic tubules and degenerating cells was significantly higher in I/R + vehicle group than that of SO group. Melatonin and CAPE significantly reduced the number of degenerating cells; additionally, melatonin reduced the number of atrophic tubules (P < 0.05). Our results indicate that myocardial I/R induces severe testicular damage and antioxidant agents, especially melatonin, have protective effects on testicular injury after myocardial I/R. Our data emphasize that oxygen-based reactants may play a central role in remote organ injury.

Published
2005
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11. Melatonin is effective in reducing stress-induced organ damage in Wistar albino rats.

Author

EŞREFOĞLU, Mukaddes, AKINCI, Ayşin, ELBE, Hülya, TAŞLIDERE, Elif, ÇETİN, Aslı, and ATEŞ, Burhan

Subjects
*MELATONIN, *PHYSIOLOGICAL stress, *PROLAPSE of bodily organs, *LABORATORY rats, *ANTIOXIDANTS, *CHEMICAL scavengers, *PREVENTION, *THERAPEUTICS
Abstract

In the present study, we tried to investigate the effects of melatonin, a novel antioxidant and a potent free radical scavenger, in stress-induced cerebral, cerebellar, cardiac, and hepatic oxidative damage using microscopic and biochemical analysis. A total of 32 male Wistar albino rats were divided into control, stress, stress + saline, and stress + melatonin groups. The rats from the stress groups were exposed to high stress conditions of starvation, immobilization, and cold exposure. The rats from the stress + melatonin group received melatonin daily at 20 mg/kg body weight intraperitoneally for 7 days. At the end of the experiment, the brain, cerebellum, heart, and liver were rapidly removed. The main histopathological damage scores (MHDSs) of the stress and stress + saline groups were higher than those of control group for all of the organs. The MHDSs of melatonin-administered group were lower than those of stress and stress + saline groups. The main tissue superoxide dismutase activities of the stress + melatonin group were even higher than those of the control group in the cerebellum and liver, and main tissue catalase activities of the stress + melatonin group were even higher than those of control group in all of the organs. As a conclusion, we found melatonin very effective in reducing stress-induced organ damage by inhibiting lipid peroxidation and supporting the cellular antioxidant defense system. [ABSTRACT FROM AUTHOR]

Published
2014
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12. Cardioprotective potential of melatonin, quercetin and resveratrol in an experimental model of diabetes

Author

Nuray Bostancieri, Mukaddes Esrefoglu, Hulya Elbe, Nigar Vardi, and EŞREFOĞLU, MUKADDES

Subjects
0301 basic medicine, Histology, Antioxidant, endocrine system diseases, medicine.medical_treatment, Resveratrol, Pharmacology, Antioxidants, Diabetes Mellitus, Experimental, Melatonin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Diabetes mellitus, Diabetic cardiomyopathy, medicine, Animals, Rats, Wistar, chemistry.chemical_classification, Reactive oxygen species, 030102 biochemistry & molecular biology, business.industry, General Medicine, Models, Theoretical, medicine.disease, Streptozotocin, official publication of the Biological Stain Commission, ss.1-6, 2021 [Bostancıeri N., Elbe H., Eşrefoğlu M., Vardı N., -Cardioprotective potential of melatonin, quercetin and resveratrol in an experimental model of diabetes.-, Biotechnic & histochemistry], Rats, Oxidative Stress, Medical Laboratory Technology, chemistry, 030220 oncology & carcinogenesis, Quercetin, business, medicine.drug
Abstract

Oxygen radicals participate in the pathogenesis of heart damage. Diabetes accelerates the formation of reactive oxygen species (ROS). We investigated the effects of the antioxidants, melatonin, quercetin and resveratrol, on cardiomyopathy and apoptosis in rats with streptozotocin (STZ) induced diabetes mellitus (DM). Rats were divided into five groups of seven: control, DM, DM + melatonin, DM + quercetin and DM + resveratrol. All treatments were begun with a single dose of STZ to induce diabetes and experimental treatments were continued daily for 30 days. Morphologic and apoptotic changes were analyzed by histological assessment. The heart tissue of the control group exhibited normal histology, whereas the heart tissue of the DM group exhibited vacuolization, necrosis, congestion, infiltration and myofibril loss. The DM group exhibited significantly increased apoptosis compared to the control group. Differences in anti-apoptotic effects were statistically significant for all three antioxidant treatment groups; the anti-apoptotic effects of quercetin and resveratrol were similar. Melatonin, resveratrol and quercetin exhibited protective effects against diabetic heart damage.

Published
2021

13. Effects of melatonin on both testicular regeneration and recovery of spermatogenesis in busulfan-treated rats

Author

E Taslidere, M Esrefoglu, OE Tok, B Taslidere, H Bulut, EŞREFOĞLU, MUKADDES, TAŞLIDERE, BAHADIR, and BULUT, HURI

Subjects
PHARMACOLOGY & TOXICOLOGY, Temel Bilimler, Basic Pharmaceutics Sciences, Life Sciences, Life Sciences (LIFE), Sağlık Bilimleri, Pharmacology and Therapeutics, Genel Farmakoloji, Toksikoloji ve Eczacılık, Temel Eczacılık Bilimleri, Yaşam Bilimleri (LIFE), Yaşam Bilimleri, Health Sciences, Farmakoloji ve Toksikoloji, Testis, FARMAKOLOJİ VE ECZACILIK, Rat, General Pharmacology, Toxicology and Pharmaceutics, Natural Sciences, Spermatogenesis, Eczacılık, PHARMACOLOGY & PHARMACY, Busulfan, Melatonin
Abstract

© 2022, Faculdade de Ciencias Farmaceuticas (Biblioteca). All rights reserved.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.

Published
2022

14. Therapeutic effects of melatonin and quercetin in improvement of hepatic steatosis in rats through supression of oxidative damage

Author

Elif Taslidere, Burhan Ates, Olgu Enis Tok, Mehmet Serif Aydin, Mukaddes Esrefoglu, Hulya Elbe, Asli Cetin, EŞREFOĞLU, MUKADDES, TAŞLIDERE, ELİF, and TOK, OLGU ENİS

Subjects
Liver Cirrhosis, 0301 basic medicine, Economics and Econometrics, medicine.medical_specialty, Cirrhosis, Necrosis, Hemorrhage, CCL4, Antioxidants, Melatonin, 03 medical and health sciences, chemistry.chemical_compound, Non-alcoholic Fatty Liver Disease, Fibrosis, Internal medicine, Materials Chemistry, Media Technology, Animals, Medicine, Rats, Wistar, Carbon Tetrachloride, Inflammation, business.industry, Forestry, medicine.disease, digestive system diseases, Rats, Oxidative Stress, 030104 developmental biology, Endocrinology, Liver, chemistry, Female, Quercetin, Steatohepatitis, Steatosis, medicine.symptom, business, medicine.drug
Abstract

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 CCI4 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 CCI4+Quercetin and CCI4+Mel groups versus CCI4 group. CAT activity of CCI4+Mel group was higher than that of CCI4 and CCI4+Quercetin groups. The mean tissue GSH level of CCI4+Mel group versus CCI4 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).

Published
2017

15. Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats

Author

Hulya Elbe, Burhan Ates, Saim Yologlu, Mukaddes Esrefoglu, Cagatay Taskapan, Nigar Vardi, and EŞREFOĞLU, MUKADDES

Subjects
Blood Glucose, Male, medicine.medical_specialty, Health, Toxicology and Mutagenesis, Blood sugar, Resveratrol, Kidney, Toxicology, Antioxidants, Blood Urea Nitrogen, Diabetes Mellitus, Experimental, Melatonin, Diabetic nephropathy, chemistry.chemical_compound, Malondialdehyde, Internal medicine, Stilbenes, medicine, Animals, Diabetic Nephropathies, Rats, Wistar, Blood urea nitrogen, ELBE H., VARDI N., Esrefoglu M., ATES B., YOLOGLU S., TASKAPAN C., -Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats.-, Human & experimental toxicology, cilt.34, ss.100-13, 2015, Superoxide Dismutase, General Medicine, Catalase, Streptozotocin, medicine.disease, Glutathione, Endocrinology, chemistry, Creatinine, Quercetin, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract

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-β1 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 damage

Published
2014

16. Melatonin is more effective than ascorbic acid and β-carotene in improvement of gastric mucosal damage induced by intensive stress

Author

Akinci, Aysin, Esrefoglu, Mukaddes, Cetin, Asli, Ates, Burhan, and EŞREFOĞLU, MUKADDES

Subjects
stress, Experimental Research, β-carotene, ascorbic acid, melatonin, AMS, cilt.11, ss.1129-36, 2015 [AKINCI A., Esrefoglu M., CETIN A., ATES B., -Melatonin is more effective than ascorbic acid and β-carotene in improvement of gastric mucosal damage induced by intensive stress.-, Archives of medical science]
Abstract

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.

Published
2015

17. Protective effects of melatonin and quercetin on experimental lung injury induced by carbon tetrachloride in rats

Author

Hulya Elbe, Elif Taslidere, Burhan Ates, Asli Cetin, Mukaddes Esrefoglu, TAŞLIDERE, ELİF, and EŞREFOĞLU, MUKADDES

Subjects
Pulmonary and Respiratory Medicine, Pulmonary Fibrosis, Clinical Biochemistry, Acute Lung Injury, Pulmonary Edema, Lung injury, Pharmacology, medicine.disease_cause, digestive system, Antioxidants, Melatonin, chemistry.chemical_compound, Malondialdehyde, parasitic diseases, medicine, Animals, Rats, Wistar, Molecular Biology, Carbon Tetrachloride, Lung, biology, Glutathione, Pneumonia, Catalase, digestive system diseases, Rats, Disease Models, Animal, Biochemistry, chemistry, Carbon tetrachloride, biology.protein, Female, Quercetin, Oxidative stress, medicine.drug
Abstract

Exposure to carbon tetrachloride (CCl4), a well-known toxicant, causes tissue damage by inducing oxidative stress via formation of free radicals. The fundamental structure of the organs of rats and humans is similar, so administration of CCl4 to rats is an accepted experimental model to produce oxidative damage to various tissues including pulmonary tissue. In this study, we evaluated the protective capacity of melatonin and quercetin against CCl4-induced oxidative lung damage in rats.Rats were divided into five groups each containing seven rats as follows: Control group, Olive oil group CCl4 group, CCl4+Melatonin, and CCl4+Quercetin group. The tissue samples were processed by routine histological and biochemical procedures. Sections were stained with Hematoxylin-eosin and Masson's trichrome. Histopathologic damage score was calculated. Malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) activities were assayed.The lung sections of control groups showed normal histological characteristics. Fibrosis, interstitial hemorrhage, epithelial desquamation in bronchiole and alveoli, intra-alveolar edema, leukocyte, and macrophage infiltration were observed in lung sections of rats exposed to CCl4 alone. The findings were reduced in the treatments groups. The MDA level in the CCI4 group were significantly higher than in the other groups (p.001), and the CAT and GSH levels in the CCI4+Mel and CCI4+Quer groups were significantly higher than in the CCI4 group (p.05).In conclusion, we suggest that agents with antioxidant properties such as melatonin and quercetin may have positive effects in the treatment of pulmonary diseases characterized by especially edema, inflammation, and fibrosis.

Published
2014

18. Not only melatonin but also caffeic acid phenethyl ester protects kidneys against aging-related oxidative damage in Sprague Dawley rats

Author

Mustafa Iraz, Mukaddes Esrefoglu, Burhan Ates, Mehmet Gul, and EŞREFOĞLU, MUKADDES

Subjects
Male, medicine.medical_specialty, Aging, Eşrefoğlu M., IRAZ M., ATES B., GÜL M., -Not only melatonin but also caffeic acid phenethyl ester protects kidneys against aging-related oxidative damage in Sprague Dawley rats.-, Ultrastructural pathology, cilt.36, ss.244-51, 2012, medicine.disease_cause, Kidney, Antioxidants, Pathology and Forensic Medicine, Superoxide dismutase, Melatonin, Rats, Sprague-Dawley, chemistry.chemical_compound, Caffeic Acids, Structural Biology, Internal medicine, medicine, Animals, Caffeic acid phenethyl ester, chemistry.chemical_classification, biology, Glutathione peroxidase, Kidney metabolism, Glutathione, Phenylethyl Alcohol, Malondialdehyde, Rats, Oxidative Stress, Endocrinology, chemistry, Cytoprotection, biology.protein, Oxidative stress, medicine.drug
Abstract

Microscopic features and antioxidant status of kidneys of young, old, and caffeic acid phenethyl ester (CAPE) and melatonin administered old Sprague Dawley rats were evaluated. Aging-related tubular and glomerular changes were evident. The most prominent tubular alterations were massive vacuole formation, mitochondrial degeneration, and lysosome accumulation. Mean tissue malondialdehyde (MDA) level was increased, mean tissue superoxide dismutase (SOD), catalase (CAT) (p < .001), and glutathione peroxidase (GPx) activities (p < .05), and total glutathione (GSH) level were decreased in old animals. Melatonin significantly reduced tissue MDA levels (p < .005), but increased tissue SOD (p < .001), CAT, and GPx activities (p < .05), and GSH levels (p < .005) in old animals. CAPE also significantly reduced tissue MDA levels (p < .005), but increased tissue SOD (p < .05), CAT (p < .005), GPx activities, and GSH levels (p < .001) in old rats. Mean tissue MDA levels of melatonin and CAPE-administered rats were even lower than those of young rats (p < .05). In conclusion, tubular and glomerular structures and tissue antioxidant enzyme activities were very well preserved in CAPE and melatonin-administered rats.

Published
2012

19. Melatonin and CAPE are able to prevent the liver from oxidative damage in rats: an ultrastructural and biochemical study

Author

Mustafa Iraz, Burhan Ates, Mehmet Gul, Mukaddes Esrefoglu, and EŞREFOĞLU, MUKADDES

Subjects
Male, medicine.medical_specialty, Antioxidant, medicine.medical_treatment, medicine.disease_cause, an ultrastructural and biochemical study.-, Ultrastructural pathology, cilt.36, ss.171-8, 2012 [Esrefoglu M., IRAZ M., ATES B., GÜL M., -Melatonin and CAPE are able to prevent the liver from oxidative damage in rats], Antioxidants, Pathology and Forensic Medicine, Melatonin, Rats, Sprague-Dawley, chemistry.chemical_compound, Caffeic Acids, Structural Biology, Internal medicine, Malondialdehyde, medicine, Animals, Caffeic acid phenethyl ester, chemistry.chemical_classification, Glutathione Peroxidase, biology, Glutathione peroxidase, Liver Diseases, Age Factors, Glutathione, Phenylethyl Alcohol, Catalase, Rats, Oxidative Stress, Endocrinology, chemistry, Liver, biology.protein, Oxidative stress, medicine.drug
Abstract

The liver continuously produces free radicals and reactive oxygen species (ROS) as part of metabolic process. These free radicals are neutralized by an elaborate antioxidant defense system consisting of enzymes and numerous nonenzymatic antioxidants like flavonoids. In this study, we have evaluated effects of melatonin and caffeic acid phenethyl ester (CAPE) to young and aged rat liver. Aging-related hepatic changes examined by light and electron microscopy and biochemical methods. Melatonin and CAPE decreased tissue malondialdehyde (MDA) levels in aged rats. Melatonin elevated tissue glutathione peroxidase (GSH-Px) activity and tGSH level, whereas CAPE elevated tissue catalase activity in aged rats. This study demonstrates that both melatonin and CAPE are beneficial in delaying age-related hepatocellular changes. Melatonin and CAPE supplementation in older ages may support liver to protect itself from various damaging agents including infectious agents and toxins.

Published
2012

20. Wistar Albino sıçanlarda strese bağlı mukoza hasarının tedavisinde maydanoz. beta karoten, melatonin, askorbik asit ve lansoprazolün etkilerinin karşılaştırmalı olarak incelenmesi

Author

Akinci, Ayşin, Eşrefoğlu, Mukaddes, and Histoloji ve Embriyoloji Anabilim Dalı

Subjects
Beta carotene, Parsley, Oxidative stress, Histology and Embryology, Stomach, Ascorbic acid, Histoloji ve Embriyoloji, Anti-ulcer agents, Cold stress, Melatonin, Rats
Abstract

Pek çok hastalığa zemin hazırlayan önemli bir faktör olan stresin neden olduğu hastalıklardan birisi de gastrik ülserdir. Mekanizması tam olarak aydınlatılmamış olan stres ülserinin patogenezinin multifaktöriyel olduğu kabul edilmektedir. Oksijen radikalleri mukoza hasarının patogenezinde rol aldıkları bilinen bileşiklerdir. Çeşitli stres modellerinin reaktif oksijen türleri (ROS) oluşumunu hızlandırdığı gösterilmiştir. Bu çalışmanın amacı, sıçanlarda açlık, soğuk stres ve hareketsizlik stresi ile oluşturulan gastrik hasarı engellemede antioksidan özellikleri bilinen maydanozun (Petroselinum crispum), melatoninin, beta-karotenin, askorbik asitin ve bir proton pompa inhibitörü olan lansoprazolün etkinliklerini karşılaştırmalı olarak araştırmaktır.Çalışmada 72 adet Wistar albino erkek sıçan 9 gruba ayrıldı: Grup 1: Kontrol, Grup 2: Stres, Grup 3: Stres+normal diyet (7 gün), Grup 4: Stres+serum fizyolojik (0,5 ml/ ip/ 7 gün), Grup 5: Stres+maydanoz (28 g/kg/ diyete ek olarak 7 gün), Grup 6: Stres+melatonin (20mg/ kg/ ip/ 7 gün), Grup 7: Stres+beta-carotene (5 mg/ kg/ gavaj/ 7 gün), Grup 8: Stres+askorbik asit (5 mg/ kg/ ip/ 7 gün) ve Grup 9: Stres+lansoprazol (0,5 mg/ kg/ gavaj/ 7 gün). Denekler 72 saat açlığı takiben +4 derecede 8 saat süreyle hareketsiz kılınarak strese maruz bırakıldılar. Doku örnekleri %10'luk nötral formalinde fikse edildi ve parafine gömüldü. Kesitler hematoksilen-eozin, PAS-Alsiyan mavisi ve Masson'nun trikrom boyası ile boyandı. Histopatolojik hasar indeksi, malondialdehit (MDA) ve glutatyon (GSH) seviyeleri, süperoksit dismutaz (SOD), katalaz (CAT) ve glutatyon peroksidaz (GSH-Px) aktiviteleri ölçüldü.Ortalama histopatolojik hasar skoru kontrol grubunda 1.5 ± 0.22 iken, stres uygulanan grupta 7.0 ± 0.57 idi (P < 0,005). Stres grubunda mukoza bütünlüğünün bozulduğu, epitelin yassılaştığı, lümene döküldüğü, bez yapısının bozulduğu, mukus tabakasının inceldiği ve dejenere alanlarda genellikle homojen bir materyalin biriktiği izlendi. Lümende çok miktarda hücresel artık görüldü. Stres grubu hariç tüm gruplarda histopatolojik skor düştü. Kontrol grubu ile stres grubu arasında doku MDA seviyesi ve CAT aktivitesinde istatistiksel olarak anlamlı fark bulundu (sırasıyla P< 0.005, P< 0.05). Stres grubunda GSH seviyesi ve SOD ve GSH-Px aktiviteleri düşüktü. Maydanoz uygulamasından sonra histopatolojik skor ve MDA seviyesi düşerken (P< 0.05), SOD (P< 0.05) ve CAT aktiviteleri ile GSH seviyesi (P< 0.05) arttı. Lansoprazol histopatolojik skorda (P< 0.005) ve MDA seviyesinde (P< 0.05) düşüşe, GSH seviyesinde ve SOD ve CAT aktivitelerinde artışa yol açtı. Melatonin histopatolojik skorda (P< 0.005) ve MDA seviyesinde (P< 0.05) düşüşe, GSH seviyesinde ve GSH-Px ve SOD (P< 0.05) aktivitelerinde artışa yol açtı. Askorbik asit histopatolojik skorda (P< 0.05) ve MDA seviyesinde (P< 0.05) düşüşe, GSH seviyesinde (P< 0.05) ve SOD (P< 0.05) ve GSH-Px aktivitelerinde artışa neden oldu. Beta-karoten uygulaması ise histopatolojik skorda (P< 0.05) ve MDA seviyesinde (P< 0.005) düşüşle, GSH seviyesinde ve SOD ve GSH-Px aktivitelerinde artışla sonuçlandı.Uyguladığımız tüm tedavi edici ajanların strese bağlı olarak ortaya çıkan gastrik hasarın giderilmesinde hücresel antioksidan savunma sistemini destekleyerek yararlı olduğu düşüncesindeyiz.Anahtar kelimler: Askorbik asit, beta karoten, lansoprazol, maydanoz, melatonin, mide, oksidatif stres, sıçan, soğuk stres. Gastric ulcer is one of the diseases caused by stress that is an important underlying factor for many diseases. The pathogenesis of stress-induced ulcer is to be considered multifactorial since its mechanism is not clear yet. Oxygen radicals have been known to be involved in the pathogenesis of gastric mucosal injury. Several stress ulcer models have been shown to increase the production of free oxygen radicals. The aim of the present study was to assess the antioxidative effects of parsley (Petroselinum crispum), melatonin, beta-carotene, ascorbic acid and, lansoprazole , a proton pomp inhibitor on stress-induced gastric mucosal injury.In the present study 72 Wistar albino male rats were divided into nine groups: Group 1: Control, Group 2: Stress, Group 3: Stress+ normal diet (7 days), Group 4: Stress+ saline (0,5 ml/ ip/ 7 days), Group 5: Stress+parsley (diet with extra 28 g/kg/7 days), Group 6: Stress+ melatonin (20 mg/ kg/ ip/ 7 days), Group 7: Stress+beta-carotene (5 mg/ kg /gavage/ 7 days), Group 8: Stress+ascorbic acid (15mg/ kg/ ip/ 7 days) and Group 9: Stress+lansoprazole (0,5 mg/ kg/ gavage/ 7 days). Stress ulcer was induced by the cold-restraint and immobilization method for 8 hours at 4°C after a starvation period of 72 hours. Tissue samples were fixed in %10 neutral buffered formalin and were embedded in parafin. Sections were stained with hematoxylin-eosin, Periodic acid Schiff-Alcian blue and Masson?s trichrom. Histopathologic damage score, malondialdehyde (MDA) and glutathione (GSH) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were assayed.Main histopathological damage score in control group was 1.5 ± 0.22, in stress group 7.0 ± 0.57 (P < 0,005). In stress group, mucosal integrity was damaged, epithelium was flattened and spilled into the gastric lumen, glandular structure was destroyed, the thickness of mucous layer was diminished and a homogenous material was accumulated within the degenaration area. High amount of debris was observed within the lumen. Histopathological damage score was decreased in all of the groups except stress group. MDA level and CAT activity were significantly different between control and stress groups (P< 0.005, P< 0.05; respectively). Parsley administration resulted in decreases in histopathological damage score and MDA level (P< 0.05) and increases in GSH level (P< 0.05) and SOD and CAT (P< 0.05) activities. Lansoprazole decreased histopathological damage score (P< 0.005) and MDA level (P

Published
2010

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