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Öğe Beneficial effects of melatonin on acetylsalicylic acid induced liver damage in rats(2017) Sarıhan, Mehmet Ediz; Parlakpınar, Hakan; Polat, Alaattin; Vardı, Nigar; Özhan, Onural; Acet, Hacı AhmetAbstract: We investigated the effects of acute high doses of acetylsalicylic acid (ASA) on liver tissue and the protective and therapeutic effects of melatonin on ASA related damage. Forty rats were randomly divided into five groups of eight: group 1, control; group 2, administered 200 mg/kg ASA; group 3, administered 5 mg/kg melatonin 45 min before ASA; group 4, administered 5 mg/kg melatonin 45 min after ASA; group 5, administered 5 mg/kg melatonin. We measured malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), myeloperoxidase (MPO) aspartate aminotransferase (AST) and alanine transaminase (ALT) in the liver. ASA treatment significantly increased MDA and MPO production, whereas it significantly decreased levels of SOD, CAT, GPx and GSH in the liver. Melatonin significantly decreased MDA and MPO production, whereas it caused increased levels of antioxidants. AST and ALT levels were higher after ASA treatment, whereas these levels were reduced significantly after melatonin administration. Our histopathological findings, including apoptosis, were consistent with the biochemical results. Melatonin exhibits beneficial effects against high dose ASA induced hepatotoxicityÖğe The Effect of Caffeic Acid Phenethyl Ester (CAPE) Against Cholestatic Liver Injury in Rats(Academic Press Inc Elsevier Science, 2010) Coban, Sacid; Yildiz, Fahrettin; Terzi, Alpaslan; Al, Behcet; Ozgor, Dincer; Ara, Cengiz; Polat, AlaattinObjectives. Caffeic acid phenethyl ester (CAPE) has been subjected to considerable investigations that have revealed its antioxidant and anti-inflammatory activities in different conditions. But there is not a previous investigation about its effect on cholestatic liver injury. The aim of this study was to investigate the effect of CAPE in rat liver against cholestatic liver injury induced by bile duct ligation. Methods. Swiss-albino rats were recruited in the study as follows; Group 1 rats subjected to simple laparotomy known as the sham group; Group 2 rats subjected to bile duct ligation (BDL); Group 3 bile duct ligated rats treated with CAPE. The third group received CAPE (10 mu mol/kg) intraperitoneally daily throughout 14 d. Results. Data showed a decrease in gamma glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase levels (ALT) of the CAPE treated rats, compared with BDL group (P < 0.001, P < 0.01, and P < 0.02, respectively). In the CAPE treated rats, tissue levels of malondialdehyde (MDA) and myeloperoxidase (MPO) were significantly lower than that of the BDL group (P < 0.001). The levels of glutathione (GSH) in CAPE treated rats were significantly higher than that of BDL group (P < 0.001). In CAPE treated group, the levels of interleukin-1alpha (IL-1 alpha) and interleukin-6 (IL-6) were significantly lower than that of BDL group (P < 0.03, P < 0.02, respectively). Administration of CAPE in the rats with biliary obstruction resulted in inhibition of necro-inflammation. Conclusion. These results suggest that treatment of CAPE maintains antioxidant defenses, reduces oxidative liver injury, cytokine damage, and necro-inflammation in bile duct ligated rats. Thus, CAPE seems to be a promising agent for the attenuation of cholestatic liver injury. (C) 2010 Elsevier Inc. All rights reserved.Öğe Effects of Benzo(a)pyrene and Ethanol on Morphology and Antioxidant Status and Transaminases in Rat Liver(2014) Emre, Mehmet Hanifi; Aktay, Göknur; Polat, Alaattin; Öztürk, FeralAbstract: Ethanol and benzo(a)pyrene cause an increase in lipid peroxidation either by producing the reactive oxygen species or decreasing the level of endogenous antioxidant enzymes that leads to cellular damage and cellular dysfunction. The aim of this study was to investigate both physiological and histological changes in liver tissue after administration of benzo(a)pyrene and ethanol. Male Sprague Dawley rats were divided into four groups. First group (control group). Second group treated with benzo(a)pyrene [B(a)P], third group treated with benzo(a)pyrene[B(a)P] plus ethanol (EtOH) and fourth group was given ethanol(EtOH). Superoxide dismutase (SOD), alanin aminotransferase (ALT), aspartat aminotransferase (AST), gamma-glutamyl transferase (GGT), glutathione (GSH), malondialdehyde (MDA) levels as well as histological examination were evaluated to demonstrate the liver response following administration of [B(a)P] and (EtOH) separately and together. SOD activities of the liver tissue in the experimental groups were decreased when compared to the first group. Activities of ALT, AST and GGT of the liver tissue in all experimental groups were found significantly higher than that of the first group. GSH levels of the liver tissue of the experimental groups were lower than the first group especially in fourth group. When we compared MDA levels among study groups, MDA levels of experimental groups were found significantly higher than the first group. Exposure [B(a)P] to resulted in hepatocellular changes in the periportal area and inflammatory cell infiltration . On the other hand, liver tissue in third group and fourth group, which was treated with [B(a)P] plus EtOH and EtOH alone respectively, showed seldom inflammatory cell infiltrations. [B(a)P] and EtOH administration alone or together discretely determined changes in the GSH, MDA levels and SOD ALT, AST and GGT enzyme activities in the liver tissues. Additionally, we noted [B(a)P] induced hepatocellular changes in the periportal area.Öğe Protective effect of low dose of melatonin against cholestatic oxidative stress after common bile duct ligation in rats(Baishideng Publ Grp Co Ltd, 2005) Esrefoglu, Mukaddes; Gul, Mehmet; Emre, Memet Hanifi; Polat, Alaattin; Selimoglu, Mukadder AyseAIM: To investigate the role of oxidative injury and the effect of exogenous melatonin administration on liver damage induced by bile duct ligation (BDL), and second, to evaluate the role of nitric oxide (NO), a free oxygen radical, in oxidative injury. METHODS: Thirty-two Sprague-Dawley rats were assigned to four groups: sham operation (SO), BDL, BDL+melatonin, and BDL+vehicle. Cholestasis was achieved by double ligature of the common bile duct. Melatonin was injected intraperitoneally 500 mu g/(kg.d) for 8 d. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA), and reduced GSH. Total nitrite (NO(X)) concentrations were determined in hepatic homogenates. Histopathological examination was performed using a histological scoring system. RESULTS: The histopathological changes including portal inflammation, necrosis, apoptosis, focal inflammation and fibrosis were severe in the BDL and BDL+vehicle groups. There were numerous large areas of coagulation necrosis. Histological Activity Index scores of these groups were significantly higher than that of the SO group. Treatment with melatonin reduced these alterations significantly. The degree of necro-inflammation and fibrosis showed significant difference between the BDL and BDL+melatonin groups. BDL was accompanied by a significant increase in MDA and NO(X), and a significant decrease in GSH levels. Mean +/- SE values of MDA, GSH and NO(X) levels of SO group were 147.47 +/- 6.69, 0.88 +/- 0.33 mu mol/g and 180.70 +/- 6.58 nm/g, respectively. The values of BDL group were 200.14 +/- 21.30, 0.65 +/- 0.02 mu mol/g, and 400.46 +/- 48.89 nm/g, respectively, whereas the values of BDL+melatonin group were 115.93 +/- 6.8, 0.74 +/- 0.02 mu mol/g, and 290.38 +/- 32.32 nm/g, respectively. Melatonin treatment was associated with a significant recovery of MDA, GSH and NO(X) levels. CONCLUSION: We have concluded that oxidative stress is associated with the pathogenesis of cholestatic liver damage and NO contributes to oxidative damage. Melatonin, even at low dose, is an efficient agent in reducing negative parameters of cholestasis. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.Öğe The protective role of molsidomine on the cisplatin Induced ototoxicity(Indian Journal of Otolaryngology and Head & Neck Surgery, 2014) Toplu, Yüksel; Parlakpınar, Hakan; Sapmaz, Emrah; Karataş, Erkan; Polat, Alaattin; Kızılay, AhmetThis experimental study was designed to investigate the protective effects of molsidomine (MOL) on against cisplatin-induced ototoxicity (CIO). To examine this effect, distortion product otoacoustic emissions (DPOAEs) measurements and serum levels of oxidative and antioxidant status [including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPX), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI)] were evaluated. Thirty-two female wistar albino rats were divided into four groups including; control (Group K), cisplatin (Group C), cisplatin plus MOL group (Group CM), and MOL group (Group M). DPOAEs measurements between 0.9961 and 8.0003 Hz as DP-gram and input/output (I/O) functions were performed in the same (left) ear of all rats on days 0, 1st, 5th and 12th. Prior to death, the last DPOAEs measurements and blood samples were taken. In the C group, statistically significant DPOAE amplitude reductions were detected at 2.5195, 3.1758, 3.9961, 5.0391, 6.3516 and 8.0039 Hz frequencies (p\0.05) between 0th and 1st, 0th and 5th and 0th and 12th days’ measurements (p\0.05). Serum level of MDA, TAC and OSI levels were significantly higher in the C group versus K group (p\0.05). In the CM group, there were no significant differences at all frequencies between 0th and other days’ measurements (p[0.05) and the serum levels of all biochemical parameters were shifted toward normal values, similar to the K group (p\0.05). No significant differences were detected in the either M or K group’s measurements. According to these results, cisplatin-related ototoxicity has been significantly prevented by MOL.Öğe The Protective Role of Molsidomine on the Cisplatin-Induced Ototoxicity(Springer India, 2014) Toplu, Yuksel; Parlakpinar, Hakan; Sapmaz, Emrah; Karatas, Erkan; Polat, Alaattin; Kizilay, AhmetThis experimental study was designed to investigate the protective effects of molsidomine (MOL) on against cisplatin-induced ototoxicity (CIO). To examine this effect, distortion product otoacoustic emissions (DPOAEs) measurements and serum levels of oxidative and antioxidant status [including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPX), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI)] were evaluated. Thirty-two female wistar albino rats were divided into four groups including; control (Group K), cisplatin (Group C), cisplatin plus MOL group (Group CM), and MOL group (Group M). DPOAEs measurements between 0.9961 and 8.0003 Hz as DP-gram and input/output (I/O) functions were performed in the same (left) ear of all rats on days 0, 1st, 5th and 12th. Prior to death, the last DPOAEs measurements and blood samples were taken. In the C group, statistically significant DPOAE amplitude reductions were detected at 2.5195, 3.1758, 3.9961, 5.0391, 6.3516 and 8.0039 Hz frequencies (p < 0.05) between 0th and 1st, 0th and 5th and 0th and 12th days' measurements (p < 0.05). Serum level of MDA, TAC and OSI levels were significantly higher in the C group versus K group (p < 0.05). In the CM group, there were no significant differences at all frequencies between 0th and other days' measurements (p[0.05) and the serum levels of all biochemical parameters were shifted toward normal values, similar to the K group (p < 0.05). No significant differences were detected in the either M or K group's measurements. According to these results, cis-platin-related ototoxicity has been significantly prevented by MOL.Öğe The Value of Tc-99m Mibi for Differential Diagnosis of Biliary Atresia and Hepatitis in Rats(2016) Koksal, İsmail; Kekilli, Ersoy; Köroğlu, Reyhan; Bati, Fatih; Polat, Alaattin; Karaman, AbdurrahmanAbstract: Cholestatic diseases in neonates which characterized by deterioration of bile passage to intestine. We investigated the usability of Tc-99m MIBI as a hepatobiliary scintigraphy radiopharmaceutical for diferential diagnosis of biliary atresia and hepatitis in experimental model. A total of 20 males Wistar albino rats who had weights ranging from 200-350 g were included in this study. Rats were randomly divided into 4 groups. Control group, sham operated group, biliary atresia group and chemical hepatitis group (with carbon tetrachloride) were created, respectively. Blood flow phases, consantration and early excreation phases was performed after an intravenous injection through the internal jugular vein of 37 MBq Tc-99m MIBI using a gamma camera. Dual late static images were obtained at the same position at 15, 30, 60, 90 and 120 min after injection. In control group, radiopharmaceutical passage into the small intestine was seen between 45 and 60 min and evidently seen between 120 and 150 min as large hyperactive focus on midline or non-linear (snaky) radiopharmaceutical accumulation at the level of kidney. In biliary atresia group, radiopharmaceutical concentration was seen normal in liver but passage into the small intestine was not seen all rats. In carbon tetrachloride group, blood flow, concentration and early excretion scintigraphic images did not differ from control group and radiopharmaceutical passage into the small intestine was seen between 45 and 60 min. Although radiopharmaceuticals passage into the intestine was not shown in all rats of biliary atresia group. We suggest that Tc-99m MIBI as a radiopharmaceutical of hepatobiliary scintigraphy would be the contribution of the differential diagnosis of biliary atresia and hepatitis in humans