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Öğe Amikacin-induced acute renal injury in rats: protective role of melatonin(Wiley, 2003) Parlakpinar, H; Ozer, MK; Sahna, E; Vardi, N; Cigremis, Y; Acet, AIt is well established that some agents such as aminoglycosides generate free oxygen radicals, leading to an increased oxireductase production, which in turn increases tissue toxicity. The aim of this study is to test whether melatonin, the chief secretory product of the pineal gland and a highly effective antioxidant and free radical scavenger, reduces the nephrotoxicity caused by amikacin (AK). Herein, we investigated the physiologic and pharmacological role of melatonin in influencing AK-induced nephrotoxicity. For this, pinealectomized (Px) and sham operated (non-Px) rats were used. Both AK and melatonin were administered to all groups. We investigated the effects of melatonin on AK-induced changes in levels of malondialdehyde (MDA), a lipid peroxidation product, glutathione (GSH), an antioxidant whose levels are influenced by oxidative stress, and blood urea nitrogen (BUN) and serum creatine (Cr) levels. Morphologic changes in the kidney were also examined by using light microscopy. MDA levels were found to be higher in Px than in non-Px AK-treated animals. Melatonin administration to Px rats reduced MDA levels. In relative to non-Px rats, Px animals treated with AK had significantly lower GSH concentrations while melatonin administration elevated GSH levels in the kidney; however, this stimulatory effect of melatonin was not observed in non-Px AK-treated rats. Treatment with AK alone resulted in significantly higher plasma Cr and BUN levels. Repeated administration of melatonin prevented the AK-induced elevation of plasma Cr and BUN levels. Morphologic damage to renal tubules as a result of AK was more severe in the renal cortex than in the medulla. The damage to the kidney induced by AK was reversed by melatonin in the Px rats. In conclusion, these results show that physiologic melatonin concentrations are important in reducing AK-induced renal damage, while pharmacologic concentrations of melatonin did not add to the beneficial effect.Öğe The attenuation of vasospasm by using a SOD mimetic after experimental subarachnoidal haemorrhage in rats(Springer Wien, 2003) Aladag, MA; Turkoz, Y; Sahna, E; Parlakpinar, H; Gul, MBackground. Delayed cerebral vasoconstriction and brain ischemia, are critical problems in the management of a patient affected by rupture of an intracranial aneurysm. Overexpression of Cu-Zn superoxide dismutase (Cu-Zn SOD) can reduce the extent of cerebral vasospasm. We, therefore investigated if vasospasm, can be prevented by a novel, stable, and cell permeable SOD mimetic, MnTBAP [Mn(III) tetrakis (4-benzoic acid) porphyrin] which permeates the biological membranes and scavenges superoxide anions and peroxynitrite. Methods. 28 rats (225-250 g) were divided equally into four groups: group 1: control; group 2: SAH only; group 3: SAH plus placebo; and group 4: SAH plus MnTBAP We used a double haemorrhage method to produce SAH. Starting six hours after SAH, 5 mg/kg MnTBAP (Calbiochem, Darmstadt-Germany; Cat. No 475870)) or an equal volume of 0.9% saline (37degreesC) was administered by intraperitoneal injection twice daily for 5 days to groups 4 and 3 respectively. MnTBAP or 0.9% saline injections were continued up to fifth day after SAH and rats were sacrificied on the fifth day. Brain sections at the level of the pons were examined by light microscopy. Planimetric measurements were made for the cross-sectional areas of the lumen and the vessel wall (intima plus media) of the basilar artery by a micrometer. Finding. Administration of MnTBAP significantly attenuated the vasoconstriction of the basilar artery in group 4 compared with the groups 2 and 3 (p<0.001). Interpretation. These results suggest that this SOD mimetic (MnTBAP) attenuates delayed cerebral vasoconstriction following experimental SAH and that superoxide anions have a role in the pathogenesis of vasospasm after SAH.Öğe Caffeic acid phenethyl ester (CAPE) attenuates cerebral vasospasm after experimental subarachnoidal haemorrhage by increasing brain nitric oxide levels(Pergamon-Elsevier Science Ltd, 2006) Aladag, MA; Turkoz, Y; Ozcan, C; Sahna, E; Parlakpinar, H; Akpolat, N; Cigremis, YBackground: Cerebral vasospasm, a medical complication of aneurysmal subarachnoid hemorrhage (SAH), is associated with high morbidity and mortality rates, even after the aneurysm has been secured surgically or endovascularly. Evidence accumulated during the last decade suggest that scavenging a vasodilator, nitric oxide (NO), by superoxide anions (O-2(-)), and activating a strong vasoconstructor, protein kinase C (PKC), are the two most important mechanisms in the pathogenesis of vasospasm. Our aim in this study was to determine whether caffeic acid phenethyl ester (CAPE), a non-toxic oxygen free radical scavenger, prevents vasospasm in an experimental rat model of SAH. Methods: Twenty eight rats (225-250 g) were divided into four groups equally: group 1, control group group 2, SAH group; group 3, SAH plus placebo group; and group 4, SAH plus CAPE group. We used double haemorrhage method for SAH groups. Starting 6 h after SAH, 10 mu mol/kg CAPE or an equal volume of 0.9% saline were administered by intraperitoneal injection twice daily for 5 days to SAH plus CAPE and SAH plus placebo groups, respectively. CAPE or 0.9% saline injections were continued up to 5th day after SAH. Rats were sacrificed on the 5th day. Brain sections at the level of the pons were examined by light microscopy. Measurements were made for the cross-sectional areas of the lumen and the vessel wall (intimae plus media) of basilar artery by a micrometer. The levels of malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) were measured in rat brain tissue. Results: Administration of CAPE significantly attenuated the vasoconstriction of the basilar artery. There were marked narrowing in the lumens of and thickening in the walls of basilar arteries in the SAH, and the SAH plus placebo compared with CAPE group (p < 0.001). We also observed that CAPE administration significantly decreased the tissue level of MDA, while significantly increased the tissue levels of GSH, NO in the SAH plus CAPE group compared to only SAH group, p < 0.05. Conclusions: Our results indicate that CAPE is effective in attenuating delayed cerebral vasoconstriction following experimental SAH. Our findings also suggest that the elevation of lipid peroxidation and reduction of NO bioavailability, resulting from the generation and the interaction of free radicals, have a significant role in the pathogenesis of vasospasm after SAH. (c) 2005 ISDN. Published by Elsevier Ltd. All rights reserved.Öğe Effect of aminoguanidine on ischemia-reperfusion induced myocardial injury in rats(Springer, 2005) Parlakpinar, H; Ozer, MK; Acet, AMyocardial ischemia-reperfusion (MI/R) has been implicated in the induction of inducible nitric oxide synthase (iNOS) that leads to increase production of nitric oxide (NO). Recently, excessive production of NO has been involved in causing myocardial injury. In our in vivo model, we examined the effects of aminoguanidine (AMG), a known iNOS inhibitor, on percentage infarct size in anaesthetized rats. A total of 14 rats were equally divided into two groups (n = 7 in each group). To produce myocardial necrosis, the left main coronary artery was occluded for 30 min, followed by 120 min of reperfusion, in anesthetized rats. AMG (200 mg kg(-1)) was given intravenously 10 min before occlusion. The volume of infarct size and the risk zone were determined by planimentry of each tracing and multiplying by the slice thickness. Infarct size was normalized by expressing it as a percentage of the area at risk. Hemodynamic parameters were measured via the left carotid artery. Compared to MI/R group, whereas AMG administration elevated mean arterial blood pressure, statistically reduced the myocardial infarct size (21 +/- 1 and 14 +/- 4%, respectively) and infract size/risk zone (53 +/- 3 and 37 +/- 5%, respectively) in rat model of ischemia-reperfusion. In conclusion, this study indicates that iNOS inhibitor, AMG, show reduction in NO's side effect in I/R injury.Öğe Effect of melatonin and atenolol on carbon monoxide cardiotoxicity(Blackwell Publishing, 2006) Mizrak, B; Celbis, O; Parlakpinar, H; Ölmez, EThe aim of this study was to define the characteristics of heart rates and myocardial changes in rats exposed to carbon monoxide (CO), and the effects of reoxygenation, atenolol (a beta-blocker) and melatonin after sublethal CO intoxication. Widespread use of beta-blockers in cardiology practice and growing literature on the positive effect of melatonin in ischaemia reperfusion lead us to question their effects in case of CO intoxication. Rats were exposed to CO. After sublethal intoxication the rats were reoxygenated with ambient air. Subsequently blood values, electrocardiographic recordings and pathological changes were examined for each groups. Five rats died after CO intoxication in the control group: no myocardial changes were seen in light microscopy However, myocardium of seven reoxygenated rats presented contraction bands. Seven reoxygenated rats pretreated with atenotol had a higher number of contraction bands of myocardial cells. Seven reoxygenated rats pretreated with melatonin had more contraction bands than reoxygenated rats. and heart rate recordings of these animals revealed a profund and sustained bradycardia. Thus, melatonin and atenolol appear to have some adverse effects in CO intoxication on the myocardial cells.Öğe Effects of aminoguanidine against renal ischaemia-reperfusion injury in rats(Wiley, 2006) Sahna, E; Parlakpinar, H; Cihan, OF; Turkoz, Y; Acet, AAminoguanidine is an inhibitor of nitric oxide synthase (NOS), with high selectivity for the inducible isoforrn (iNOS). In addition to being all inhibitor of NOS, aminoguanidine also exhibits antioxidant activity. Recent studies suggest that aminoguanidine reduces ischaemia-reperfusion (I/R)-induced damage. However, the role of aminoguanidine, in renal injury associated with I/R remains unknown. This Study was designed to investigate the effects of aminoguanidine on renal I/R injury. There were three groups of eight rats each. I/R was induced by occlusion of the left renal vessels for 60 min, followed by 24 h reperfusion in rats. Malondialdehyde (MDA) levels, a stable metabolite of the free radical-mediated lipid peroxidation cascade, were found to be significantly higher in the I/R group (30.3 +/- 0.1 nmol g(-1) tissue) than in the control group (10 +/- 0.05 nmol g(-1)). Aminoguanidine (100 mg kg(-1)) administration to rats significantly reduced the MDA values. We also demonstrated that I/R leads to structural change but aminoguanidine did not reverse this change. Aminoguanidine, according to the biochemical finding is protective but histopathological findings did not reveal protection against I/R injury in kidney. The effects of aminoguanidine on I/R-induced damage remain a subject for future investigations. Copyright (c) 2004 John Wiley & Soils, Ltd.Öğe Effects of melatonin and caffeic acid phenethyl ester on testicular injury induced by myocardial ischemia/reperfusion in rats(Wiley, 2005) Esrefoglu, M; Gül, M; Parlakpinar, H; Acet, AExperimental 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.Öğe The effects of melatonin on focal cerebral ischemia-reperfusion model(Saudi Med J, 2004) Kavakli, A; Sahna, E; Parlakpinar, H; Yahsi, S; Ogeturk, M; Acet, A[Abstract Not Available]Öğe Effects of pinealectomy and exogenous melatonin on rat hearts(Elsevier Gmbh, 2004) Muzrak, B; Parlakpinar, H; Acet, A; Turkoz, YThe effects of pinealectomy and administration of melatonin, the major secretory product of the pineal gland, which is a direct free radical scavenger and an indirect antioxidant, were studied in rat hearts on the basis of cardiac morphology and biochemical findings. Three groups of Wistar rats were used: one group was the shamoperated control, one group consisted of pinealectomized rats and one group consisted of pinealectomized rats that were treated with melatonin. Serum cholesterol, tissue levels of malondialdehyde (MDA) and reduced glutathione (GSH), and heart weight were determined. Histochemical staining with the Van Gieson, PAS/ Alcian blue at pH 2.5 and Masson's trichrome methods were performed in addition to hematoxylin-eosin staining. Levels of serum cholesterol and tissue MDA, and heart weight were increased in pinealectomized rats whereas GSH levels did not change. Melatonin administration reversed these effects. Microscopically, myocardial fibrosis and myxomatous degeneration of cardiac valves were detected in all pinealectomized rats. It can be concluded that pineatectomy of rats causes morphological changes in rat hearts, and short-term application of metatonin does not reverse these changes. (C) 2003 Elsevier GmbH. All rights reserved.Öğe Efficacy of melatonin as protectant against oxidative stress and structural changes in liver tissue in pinealectomized rats(Urban & Fischer Verlag, 2004) Sahna, E; Parlakpinar, H; Vardi, N; Cigremis, Y; Acet, APrevious observations demonstrated that physiological levels of metatonin, the pineal secretory product, are important in protecting against oxidative stress-induced tissue damage. We investigated the effects of pinealectomy and administration of exogenous melatonin on liver tissue in rats. Pinealectomized (Px) and sham-operated (non-Px) rats were used. We evaluated structural changes, reduced glutathione (GSH) levels and matondialdehyde (MDA) levels. Rats were divided into three groups (10 rats in each group): control. (non-Px), Px+vehicle and Px+metatonin (4 mg/kg given daily intraperitoneally for 10 days). Liver GSH levels were significantly tower in Px rats than in the control group. Melatonin administration significantly increased GSH levels (p<0.05). Px caused a significant increase in MDA levels as compared with the control group and metatonin administration to Px rats significantly reduced MDA levels in the liver (p<0.05). Sinusoidal dilatation to a varying degree developed in all Px rats. Severity of mononuclear cell. infiltration and sinusoidal congestion were tower in Px+melatonin group than in the Px group. These findings suggest that a significant increase in oxidative and structural changes occur in rat livers after pinealectomy, which can be diminished by melatonin treatment. (C) 2004 Published by Elsevier GmbH.Öğe Gentamicin-induced nephrotoxicity and protective effect of caffeic acid phenethyl ester in rats(Wiley, 2005) Vardi, N; Parlakpinar, H; Ozturk, F; Acet, AThe objective of this study was to investigate the beneficial effects of caffeic acid phenethyl ester (CAPE) on gentamicin (GM)-induced nephrotoxicity in Wistar rats. Twenty-one adult Wistar rats were divided into three groups as follows: control group, GM and GM + CAPE group. Control group rats were injected with 5% ethanol, GM group rats were treated with 100 mg/kg GM and GM + CAPE group were pretreated with 10 mu mol/kg CAPE for 2 days, then exposed to GM at the same dose. Drug injections were applied for 12 days. Twenty-four hours after the last injection, rats were killed and kidneys were quicky removed. Tissue malondialdehyde (MDA) measurements and microscopic examination of kidneys were performed. In the GM group, significant increases in MDA levels were observed (P < 0.05). These changes were found to be normalized in the GM + CAPE group. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules were found to be prevented by CAPE pretreatment. In conclusion, CAPE exerted an improvement on GM-induced nephrotoxicity, possibly, at least in part through inhibition of the production of oxygen free radicals that cause lipid peroxidation.Öğe Inhibition of experimental proliferative vitreoretinopathy with protein kinase C inhibitor (chelerythrine chloride) and melatonin(Karger, 2006) Er, H; Turkoz, Y; Mizrak, B; Parlakpinar, HPurpose: To investigate whether a protein kinase C (PKC) inhibitor and melatonin prevent proliferative vitreoretinopathy (PVR). Methods: Twenty pigmented rabbits were used in this study. All rabbits except controls received an intravitreal injection of 0.15 ml (75,000 units) of platelet-rich plasma into their left eye. The animals were divided into four groups: group I was treated with intravitreal injection of 0.15 ml (100 mu mol/ ml) of PKC inhibitor ( chelerythrine chloride), group II received 1 ml (4 mg/kg) of intraperitoneal melatonin for 3 days, group III received nothing (blank group), and group IV (control group) received only 0.5 ml of 1% ethanol intraperitoneally for 3 days. Proliferative changes were graded in a masked fashion by indirect ophthalmoscopy for a 15-day follow-up period. The malondialdehyde (MDA), reduced glutathione (GSH) and total nitrite levels were measured in the itreous humor. Results: The grades of PVR were A and B in group I and II, treated with PKC inhibitor and melatonin, respectively. The PVR grade in the blank group was C-D. The mean MDA level in group I (4.2 +/- 0.9 mu mol/ l) was significantly lower than in the blank group (6.0 +/- 1.0 mu mol/ l; p < 0.05). The mean GSH level in group I (66.3 +/- 8.8 mu mol/ l) was not significantly different from that in the blank group (p > 0.05). The MDA and GSH levels in group II were 3.2 +/- 0.7 and 70.1 +/- 13.3 mu mol/ l, respectively. Both these levels were significantly different from those of the blank group (p < 0.05). The NO levels in both treatment groups were significantly lower than in the blank group (p < 0.001). Conclusion: These findings suggest an inhibitory effect of PKC inhibitor and melatonin on PVR. The inhibition of PVR development was associated with lower MDA and NO levels with higher GSH levels in the treatment groups. Copyright (c) 2006 S. Karger AG, Basel.Öğe Ischemia-reperfusion leads to depletion of glutathione content and augmentation of malondialdehyde production in the rat heart from overproduction of oxidants: Can caffeic acid phenethyl ester (CAPE) protect the heart?(Springer, 2005) Ozer, MK; Parlakpinar, H; Cigremis, Y; Ucar, M; Vardi, N; Acet, ADuring restoration of blood flow of the ischemic heart induced by coronary occlusion, free radicals cause lipid peroxidation with myocardial injury. Lipid peroxidation end-products, such as malondialdehyde (MDA), have been used to assess oxygen free radical-mediated injury of the ischemic-reperfused (I/R) myocardium in rats. This experimental study assessed the preventive effect of caffeic acid phenthyl ester (CAPE), antioxidant, on I/R-induced lipid peroxidation in the rat heart. We are also interested in the role of CAPE on glutathione (GSH) levels, an antioxidant whose levels are influenced by oxidative stress. I/R leads to the depletion of GSH which is the major intracellular nonprotein sulphydryl and plays an important role in the maintenance of cellular proteins and lipid in their functional state and acts primarily to protect these important structures against the threat of oxidation. In addition, we also examined morphologic changes in the heart by using light microscopy. The left coronary artery was occluded for 30 min and then reperfused for 120 min more before the experiment was terminated. CAPE (50 mu M kg(-1)) was administered 10 min prior to ischemia and during occlusion by infusion. At the end of the reperfusion period, rats were sacrificed, and the heart was quickly removed for biochemical determination and histopathological analysis. I/R was accompanied by a significant increase in MDA production and decrease in GSH content in the rat heart. Administration of CAPE reduced MDA production and prevented depletion of GSH content. These beneficial changes in these biochemical parameters were also associated with parallel changes in histopathological appearance. These findings imply that I/R plays a causal role in heart injury due to overproduction of oxygen radicals or insufficient antioxidant and CAPE exert cardioprotective effects probably by the radical scavenging and antioxidant activities.Öğe Melatonin protects against myocardial doxorubicin toxicity in rats: role of physiological concentrations(Wiley, 2003) Sahna, E; Parlakpinar, H; Ozer, MK; Ozturk, F; Ozugurlu, F; Acet, ADoxorubicin (Dox) is a widely used antineoplastic drug. Oxygen radical-induced injury of membrane lipids is considered to be the most important factor responsible for the development of Dox-induced cardiotoxicity. The pineal secretory product, melatonin, is known to be a potent free radical scavenger and its pharmacological concentrations have been shown to reduce Dox-induced cardiac damage. However, the physiological role of melatonin in the prevention of this damage is unknown. We investigated physiological and pharmacological effects of melatonin on Dox-induced changes in the levels of malondialdehyde (MDA), a lipid peroxidation product, and morphological changes in heart. Rats were pinealectomized (Px) or sham-operated ( control) 2 months before the studies. Melatonin was administered [ 4 mg/kg, intraperitoneally (i.p.)] 1 hr before or 24 hr after the administration of a single dose of Dox ( 20 mg/kg, i.p.) and continued for 2 days. The levels of MDA Dox was found to be significantly higher in the Px rats (55.9 +/- 0.6 nmol/g tissue) than intact control animals (42.6 +/- 0.4). Dox administration to Px and non-Px rats significantly increased the MDA levels. Pre- and post-treatment with melatonin in both Px and intact rats significantly reduced MDA levels. Morphological changes parallelled the MDA alterations. These findings strongly suggest that both physiological and pharmacological concentrations of melatonin are important in protecting the heart from Dox-induced damage in rats. It would seem valuable to test melatonin in clinical trials for prevention of possible heart damage associated with Dox.Öğe Myocardial ischemia/reperfusion-induced oxidative renal damage in rats: Protection by caffeic acid phenethyl ester (cape)(Lippincott Williams & Wilkins, 2005) Ozer, MK; Parlakpinar, H; Vardi, N; Cigremis, Y; Ucar, M; Acet, AMyocardial ischemia-reperfusion (MI/R) may induce renal damage. A rat model of M/IR injury was established. The left coronary artery was clamped for 30 min, constituting the ischemic period, and was then released for 120 min, thus constituting the reperfusion period. The purpose of this study was to evaluate the effects of caffeic acid phenethyl ester (CAPE), an antioxidant, on renal dysfunction in rats undergoing MI/R. CAPE (50 mu mol/kg) was administered by infusion 10 min before ischemia and during occlusion. Hemodynamic changes were recorded during the different periods. At the end of the reperfusion period, rats were sacrificed, and the kidneys were quickly removed for biochemical determination and histopathological analysis. MI/R was accompanied by a significant increase in malondialdehyde (MDA) production and decrease in glutathione (GSH) content in the rat kidney. Administration of CAPE reduced MDA production and prevented depletion of GSH content. These beneficial changes in these biochemical parameters were also associated with parallel changes in histopathological appearance. These findings imply that MI/R plays a causal role in kidney injury through overproduction of oxygen radicals or insufficient antioxidant, and CAPE exerts renal-protective effects probably by its radical scavenging and antioxidant activities.Öğe Physiological and pharmacological concentrations of melatonin protect against cisplatin-induced acute renal injury(Blackwell Munksgaard, 2002) Parlakpinar, H; Sahna, E; Ozer, MK; Ozugurlu, F; Vardi, N; Acet, ACisplatin [cis -diaminedichloroplatinum(II), CDDP] is a widely used antineoplastic drug. However, it has major side-effects such as acute tubular necrosis (ATN). There are a number of studies concerning the role of reactive oxygen radical species in the pathophysiology of CDDP-dependent ATN. Several antioxidant agents have been reported to prevent this side-effect but there is no study regarding the protective action of either physiological or pharmacological concentrations of melatonin. Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger and indirect antioxidant. We investigated the effects of melatonin on CDDP-induced changes of renal malondialdehyde (MDA), a lipid peroxidation product, and blood urea nitrogen (BUN) and serum creatine (Cr). The morphological changes in kidney were also examined using light microscopy. The rats were divided into two groups: pinealectomized (Px) and sham-operated (non-Px). Both CDDP and melatonin were administered to all groups. MDA levels were found to be higher in Px than non-Px animals. CDDP administration to Px or non-Px rats increased renal MDA levels and melatonin administration either before or after CDDP injection caused significant decreases in MDA in kidney compared with those in rats treated with CDDP alone. Serum levels of BUN and Cr did not change as a result of any treatment. Morphological tubule damage because of CDDP was more severe in the renal cortex than in the medulla. The damage to the kidney induced by CDDP was reversed by melatonin. The results show that pharmacological and physiological concentrations of melatonin reduce CDDP-induced renal injury.Öğe Potent therapeutic effect of melatonin on aging skin in pinealectomized rats(Wiley, 2005) Esrefoglu, M; Seyhan, M; Gül, M; Parlakpinar, H; Batçioglu, K; Uyumlu, BIt 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.Öğe Protective effect of aminoguanidine against nephrotoxicity induced by amikacin in rats(Springer, 2004) Parlakpinar, H; Koc, M; Polat, A; Vardi, N; Ozer, MK; Turkoz, Y; Acet, AAminoglycoside antibiotics have long been used in antibacterial therapy. Despite their beneficial effects, aminoglycosides have considerable nephrotoxic and ototoxic side effects. It has been reported that reactive oxygen radical species (ROS) play role in the pathophysiology of aminoglycosides-induced nephrotoxicity. Aminoguanidine (AG) is an effective antioxidant and free radical scavenger which has long been known to protect against nephrotoxicity. We investigated the effects of AG on amikacin (AK)-induced changes of renal malondialdehyde (MDA), glutathione (GSH), blood urea nitrogen (BUN), serum creatinine (Cr) and albumin (Alb) which are used to monitor the development of renal tubular damage. Morphological changes in the kidney were also examined using light microscopy. A total of 21 rats were equally divided into three groups which were: (1) injected with saline, (2) injected with AK, and (3) injected with AK + AG, respectively. AK administration to control rats increased renal MDA and decreased GSH levels. AG administration before AK injection caused significant decreases in MDA and increases in GSH levels in kidneys compared to rats treated with AK alone. The serum BUN level increased slightly, Cr and serum Alb did not change as a result of any treatment. AG tended to decrease the level of serum BUN and did not cause any change in Alb or Cr levels. Morphological changes, including glomerular, tubular epithelial alterations and interstitial edema, were clearly observed in AK-treated rats. In addition, AG reversed the morphological damage to the kidney induced by AK. The results show that AG has a protective effect on nephrotoxicity induced by AK and may therefore improve the therapeutic index of AK.Öğe Protective effect of caffeic acid phenethyl ester (CAPE) on myocardial ischemia-reperfusion-induced apoptotic cell death(Elsevier Ireland Ltd, 2005) Parlakpinar, H; Sahna, E; Acet, A; Mizrak, B; Polat, AOcclusion of coronary artery causes cardiomyocyte dysfunction. Reperfusion relieves ischemia by providing cells with metabolites and oxygen, thereby preventing extensive tissue damage. Although reperfusion salvages the myocardium, it also initiates a series of events including myocardial apoptosis and necrosis. The common inducers of apoptosis include reactive oxygen species (ROS). Caffeic acid phenethyl ester (CAPE) is known as an antioxidative, anti-inflammatory effects, may protect myocardial ischemia-reperfusion (MI/R)-induced apoptosis. We have previously reported that CAPE reduced MI/R-induced necrosis. Therefore, this study was focused to investigate protective effect of CAPE on the distinct form of cell death; apoptosis in an in vivo rat model. To produce MI/R, a branch of the descending left coronary artery was occluded for 30 min followed by 2 h reperfusion. ECG changes, blood pressure (BP), and heart rate (HR) were measured before occlusion and continued both occlusion and reperfusion. CAPE (50 mu mol/kg) was given 10 min before ischemia via juguler vein. Extensive formation of DNA strand breaks, the typical biochemical feature of apoptosis, was detected with the use of the terminal deoxynucleotidyl transferase (TdT)-mediated d UTP-biotin nick and labeling (TUNEL) method. Also, cysteine aspartate specific proteinase (caspase)-3 and caspase-9 activities a universal effector of apoptosis, were determined. Trunk blood was extracted to determine the serum contents related to oxidant-antioxidant status. In hemodynamic parameters, there was no significant difference in HR or BP values among any group. CAPE administration had no a significant effect on hemodynamic parameters during ischemia or reperfusion. Control group revealed extensive TUNEL-positive cardiomyocytes especially in free wall of left ventricule, interventiculare septum and nearly apex zone. Intensity of TUNEL-positive cardiomyocytes reduced as a result of CAPE treatment compared to control group in the same sections. Result of the caspase activities was found to correlate with TUNEL evaluation. CAPE also, ameliorated antioxidant status. We propose that CAPE acts in the heart as a potent scavenger of free radicals to prevent the apoptotic effect of I/R. Further studies are needed to elucidate the mechanisms of apoptotic death machinery. (C) 2004 Elsevier Ireland Ltd. All rights reserved.Öğe Protective effect of chelerythrine on gentamicin-induced nephrotoxicity(Wiley, 2006) Parlakpinar, H; Tasdemir, S; Polat, A; Bay-Karabulut, A; Vardi, N; Ucar, M; Yanilmaz, MDespite their beneficial effects, aminoglycosides including gentamicin (GEN) have considerable nephrotoxic side-effects. The toxicity of GEN at the level of the kidney seems to relate to the generation of reactive oxygen species (ROS). ROS have been reported to be involved in the activation of protein kinase C (PKC). The unique structural aspects of PKC cause it to function as a sensor for oxidative stress. It seems likely that the increased NAD(P)H oxidase-derived superoxide (O-2) production is at least in part mediated by PKC. We investigated the effects of chelerythrine, a commonly used PKC inhibitor, on GEN-induced changes of renal malondialdehyde (MDA), nitric oxide (NO) generation, catalase (CAT), superoxide disniutase (SOD), glutathione peroxidase (GSH-Px) activities, glutathione (GSH) content, and serum creatinine (Cr), blood urea nitrogen (BUN) levels. Morphological changes in the kidney were also examined. GEN administration to control rats increased MDA and NO generation but decreased CAT, SOD and GSH-Px activities, and GSH content. Chelerythrine administration with GEN caused significantly decreased MDA, NO generation and increased CAT, SOD and GSH-Px activities, and GSH content when compared with GEN alone. Chelerythrine also significantly decreased serum Cr and BUN levels. Morphological changes in the kidney including tubular necrosis were evaluated qualitatively. Both biochemical findings and histopathological evidence showed that administration of chelerythrine reduced the GEN-induced kidney damage. We propose that chelerythrine acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GEN via the inhibition of a PKC pathway. Copyright (c) 2004 John Wiley & Sons, Ltd.
