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Öğe Does dipyrone produce anxiolytic-like effects in mice?(Cukurova Univ, Fac Medicine, 2019) Topuz, Ruhan Deniz; Gunduz, Ozgur; Dokmeci, Dikmen; Karadag, Cetin Hakan; Ulugol, AhmetPurpose: Paracetamol has been shown to exert anxiolytic-like effects mediated by endocannabinoids via cannabinoid CB1 receptors. Dipyrone is an analgesic with similar effects to paracetamol rather than non-steroidal anti-inflammatory drugs. Involvement of central structures to its effects are long under debate, whereas recent findings suggesting contribution of cannabinoid CB1 receptors to its antinociceptive effect support this argument. Taken together, the purpose of this study was to investigate whether dipyrone possesses anxiolytic-like behavior; contribution of cannabinoid CB1 and CB2 receptors and TRPV1 receptors will be determined in case of observing any effect of dipyrone in anxiety tests. Material and Methods: Balb-c mice effects of dipyrone (150, 300, 600 mg/kg, i.p) were assessed in three-chamber social interaction, open-field, elevated plus-maze and rota rod tests. The cannabinoid CB1 antagonist AM251 (1 mg/kg i.p.), the CB2 antagonist SR 144528 (1 mg/kg i.p.) and the TRPV1 antagonist capsazepine (3 mg/kg i.p) were going to be administered before dipyrone injections if any effect of dipyrone occurs. Results: Dipyrone had no effect at any dose in behavioral tests (three-chamber social interaction, open-field, elevated plus-maze and rota rod tests). Therefore, dipyrone is not tested together with the cannabinoid CB1 and CB2 antagonists and the TRPV1 receptor antagonist. Conclusion: Unlike paracetamol, dipyrone did not possess anxiolytic-like effects in mice. Discrepancies in experimental models and methodologies may be the reason of our results.Öğe Effect of curcumin on ipsilateral and contralateral testes after unilateral testicular torsion in a rat model(Karger, 2008) Basaran, Umit Nusret; Dokmeci, Dikmen; Yalcin, Omer; Inan, Mustafa; Kanter, Mehmet; Aydogdu, Nurettin; Turan, NesrinObjective: The aim of the study was to determine the protective effect of curcumin on testicular ischemia- reperfusion ( I/ R) injury. Materials and Methods: 32 male rats were divided into four groups ( n = 8): group 1: control; group 2: ischemia; group 3: I/ R, and group 4: I/ R+CUR. Curcumin ( 150 mg/ kg, p. o.) was administered before 30 min of reperfusion in group 4. Malondialdehyde ( MDA) levels, Johnsen's testicular biopsy scores, and mean seminiferous tubule diameter measurements were evaluated in testes. In addition, endothelial nitric oxide synthase ( eNOS) and inducible nitric oxide synthase ( iNOS) expressions were evaluated immunohistochemically. Results: MDA levels in control groups were significantly lower than other groups in ipsilateral and contralateral testes. Johnsen's scores in the control group were significantly higher than in other groups. MDA levels and Johnsen's scores in the I/ R+ CUR group were similar to the ischemia and I/ R groups in ipsilateral and contralateral testes. The immunoreactivity of iNOS and eNOS were increased in I/ R ipsilateral testicular groups. After I/ R, iNOS and eNOS expression increased slightly in contralateral groups. Additionally, the curcumin treatment decreased iNOS and eNOS immunoreactivity in ipsilateral and contralateral testes. Conclusion: The results suggest that curcumin did not protect the unilateral nor contralateral testes. This observation may depend on inhibition of iNOS and eNOS due to inhibition of the antioxidant, anti- inflammatory effects of nitric oxide. Copyright (C) 2008 S. Karger AG, Basel.Öğe Endocannabinoid and N-acylethanolamide levels in rat brain and spinal cord following systemic dipyrone and paracetamol administration(Canadian Science Publishing, 2019) Topuz, Ruhan Deniz; Gunduz, Ozgur; Karadag, Cetin Hakan; Dokmeci, Dikmen; Ulugol, AhmetThe cannabinoid system has been suspected to play a role in the mechanisms of action of dipyrone and paracetamol. Our purpose was to measure the local endocannabinoid and N-acylethanolamide levels in the brain and spinal cord of rats following dipyrone and paracetamol administration. Nociception was assessed 1, 5, and 12 h following drug injections in Wistar rats, using tail-flick and hot-plate tests. The antinociceptive effects of dipyrone (150, 300, and 600 mg/kg, i.p.) and paracetamol (30, 100, and 300 mg/kg, i.p.) were observed. After administration of the highest doses of dipyrone and paracetamol, endocannabinoid (N-arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG)) and N-acylethanolamide (palmitoylethanolamide (PEA), oleoylethanolamide (OEA)) levels were measured in the periaqueductal gray (PAG), rostral ventromedial medulla (RVM), and spinal cords of rats using tandem mass spectrometry with liquid chromatography. Increased 2-AG levels were observed in the PAG and the RVM 12 h after paracetamol injection; dipyrone exerted no action on 2-AG levels. Analgesic administrations led to a reduction in AEA levels in the RVM and spinal cord; similar decreases in PEA and OEA levels were observed in the RVM and the spinal cord. Dipyrone and paracetamol administrations appear to exert complicated effects on endocannabinoid and N-acylethanolamide levels in rats.Öğe Methylene blue increases contralateral testicular ischaemia-reperfusion injury after unilateral testicular torsion(Wiley, 2008) Inan, Mustafa; Basaran, Umit N.; Dokmeci, Dikmen; Yalcin, Omer; Aydogdu, Nurettin; Turan, NesrinTesticular ischaemia-reperfusion injury is commonly seen in childhood. Infertility occurs in 25% of patients after unilateral testicular ischaemia. It is has been reported that methylene blue has a positive effect in the reparation of ischaemia-reperfusion injury in different tissues. Therefore, we hypothesized that methylene blue may prevent the hazardous effects of ischaemia-reperfusion injury in testicular tissue after unilateral testicular torsion. Thirty-two prepubertal Wistar-albino rats were divided into four groups. Testicular torsion was created by rotating the right testis 720 degrees in a clockwise direction for 5 h in all groups except for Group C, which was the sham control group. In Group T, bilateral orchiectomy was performed following the torsion period. In Group TD, both testes were removed 5 days after the torsion period. In Group MB, methylene blue (1 mg/kg, i.p.) was administered 40 min before detorsion and once daily over 5 days; then, both testes were harvested. Tissue levels of malondialdehyde (MDA), serum levels of creatine kinase (CK), mean testicular biopsy score (MTBS) and mean seminifer tubule diameter (MSTD) were determined. There was a significant difference in MTBS between Groups T and TD (P < 0.05) in both ipsilateral and contralateral testes. In the contralateral testis, treatment with methylene blue decreased MTBS and MSTD (P < 0.05) and increased MDA levels (P < 0.05). In Group T, mean serum CK concentrations were higher than in any of the other groups (P < 0.05). After 5 h of unilateral testicular torsion and a 5 day reperfusion period, serious tissue damage occurred on both the ipsilateral and contralateral sides. Serum CK concentrations may be an indicator for ischaemia, but not for ischaemia-reperfusion injury. Contrary to our hypothesis, methylene blue increased contralateral testicular damage after unilateral testicular torsion and exacerbated oxidative events.Öğe Oxidative Stress and Testicular Torsion(Springer, 2012) Dokmeci, DikmenTesticular torsion is a medical urologic syndrome that constitutes a surgical emergency affecting newborns, children, and adolescent boys. The main pathophysiological event in testicular torsion is ischemia (torsion) followed by reperfusion (detorsion) of the testis, and multifactorial mechanisms seem to mediate this condition. Testicular damage after ischemia/reperfusion (I/R) is related to the duration of ischemia and to the severity of the torsion. I/R injury is associated with activation of neutrophils, inflammatory cytokines, and adhesion molecules with increased thrombogenicity, release of massive intracellular calcium, and overgeneration of reactive oxygen species and reactive nitrogen species. Although the results are not conclusive and the molecular mechanism by which antioxidants control male fertility have not yet been clearly identified, several antioxidant enzymes and antioxidant drugs have been studied to prevent such I/R injury in testis. Antioxidant therapy may represent a new option within a broader therapeutic strategy in testicular torsion with oxidative stress-mediated infertility.Öğe The Protective Effect of Curcumin on Ionizing Radiation-induced Cataractogenesis in Rats(Galenos Publ House, 2012) Ozgen, Seher Cimen; Dokmeci, Dikmen; Akpolat, Meryem; Karadag, Cetin Hakan; Gunduz, Ozgur; Erbas, Hakan; Benian, OmerObjective: The aim of the study was to determine the protective effect of curcumin against ionizing radiation-induced cataract in the lens of rats. Material and Methods: Rats were divided into six groups. Group 1: Control, Group 2: Dimethyl sulfoxide (DMSO), Group 3: DMSO+curcumin, Group 4: Irradiation, Group 5: Irradiation+DMSO, Group 6: Irradiation+DMSO+curcumin. A 15 Gy total dose was given to 4, 5, 6 groups for radiation damage. Curcumin (100 mg/kg) was dissolved in DMSO and given by intragastric intubation for 28 days. At the end of the experiment, lenses were graded and enucleated. The lenticular activity of the antioxidant enzymes, total antioxidant and glutathione peroxidase (GSH-Px), and the malondialdehyde (MDA) were measured. Results: 100% Cataract was seen in the irradiation group. Cataract rate fell to 40% and was limited at grade 1 and 2 in the curcumin group. In the irradiation group, antioxidant enzyme levels were decreased, MDA levels were increased. There was an increase in antioxidant enzyme levels and a significant decrease in MDA in the group which was given curcumin. Conclusion: Curcumin has antioxidant and radioprotective properties and is likely to be a valuable agent for protection against ionizing radiation. Hence, it may be used as an antioxidant and radioprotector against radiation-induced cataractogenesis.Öğe Protective effect of L-carnitine on testicular ischaemia-reperfusion injury in rats(Wiley, 2007) Dokmeci, Dikmen; Inan, Mustafa; Basaran, Umit Nusret; Yalcin, Omer; Aydogdu, Nurettin; Turan, Fatma Nesrin; Uz, Yesim HulyaTesticular torsion is a urological emergency referred to as acute scrotum', because inappropriate treatment can lead to male subfertility and infertility. A possible cause of testicular damage is the ischaemia-reperfusion (I/R) injury attributed to oxygen free radicals. L-carnitine, a vitamin-like antioxidant, plays a pivotal role in the maturation of spermatozoa within the reproductive tract. The aim of the present paper was to determine the protective effect Of L-carnitine on testicular I/R-induced injury. Thirty-two male rats were divided into 4 groups (n = 8). Testicular torsion was created by rotating the right testis 720 degrees in a clockwise direction. Group 1: sham-operated control; group 2: ischaemia; group 3: I/R; group 4: ischaemia-L-camitine treatment-reperfusion group. L-carnitine (500mg kg(-1), intraperitoneally) was administered before 30 min of detorsion in Group 4. After torsion (5 h) and detorsion (5 h), bilateral orchidectomy was performed. The malondialdehyde (MDA) level was evaluated in testes. Histopathologically, Johnsen's spermatogenesis criteria and mean seminiferous tubule diameter (MSTD) measurements were used. Testicular MDA levels were higher in the torsion group compared to the sham-control group (p < 0.05). Detorsion (reperfusion) caused a further increase in MDA levels (p < 0.05). Pretreatment with L-camitine prevented a further increase in MDA levels (p < 0.05). Histologically, torsion caused some separation among germinal cells in the seminiferous tubules, which became much more prominent in the I/R group but was attenuated with L-carnitine pretreatment. In conclusion, L-carnitine pretreatment may have a protective effect in experimental testicular torsiondetorsion model in rats by its well-known antioxidant potential. Copyright (C) 2006 John Wiley & Sons, Ltd.Öğe Protective Effects of Ibuprofen and L-Carnitine Against Whole Body Gamma Irradiation-Induced Duodenal Mucosal Injury(Galenos Publ House, 2011) Akpolat, Meryem; Topcu-Tarladacalisir, Yeter; Dokmeci, Dikmen; Turan, Fatma Nesrin; Uzal, Mustafa CemObjective: Ibuprofen and L-carnitine have been demonstrated to provide radioprotective activity to the hamster against whole body sublethal irradiation. The purpose of this study is to test those antioxidant drugs, each of which has the capacity of inhibiting mucosal injury, as topical radioprotectants for the intestine. Material and Methods: The male hamsters were divided into the following four groups (n=6): group 1: control group, received saline, 1 ml/100 g by gavage, as placebo. Group 2: irradiated-control group, received whole body irradiation of 8 Gy as a single dose plus physiological saline. The animals in groups 3 and 4 were given a daily dose of 10 mg/kg of ibuprofen and 50 mg/kg of L-carnitine for 15 days respectively, before irradiation with a single dose of 8 Gy. Twenty-four hours after radiation exposure, the hamsters were sacrificed and samples were taken from the duodenum, and the histopatological determinations were carried out. Results: Morphologically, examination of the gamma irradiated duodenum revealed the presence of shortening and thickening of villi and flattening of enterocytes, massive subepithelial lifting. Pretreatment of ibuprofen and L-carnitine with irradiation reduced these histopathological changes. Conclusion: Ibuprofen and L-carnitine administrated by the oral route may be a good radioprotector against small intestinal damage in patients undergoing radiotherapy.Öğe Protective effects of ibuprofen on testicular torsion/detorsion-induced ischemia/reperfusion injury in rats(Springer Heidelberg, 2007) Dokmeci, Dikmen; Kanter, Mehmet; Inan, Mustafa; Aydogdu, Nurettin; Basaran, Umit Nusret; Yalcin, Omer; Turan, Fatma NesrinThe aim of this study was to investigate the protective effect of ibuprofen on testicular torsion/detorsion induced ischemia/reperfusion (I/R) injury. A total of 48 prepubertal male Wistar albino rats were divided into two models: early and late orchiectomy. Testicular torsion was created by rotating the right testis 720 degrees in a clockwise direction. The ischemia period was 5 It and orchiectomy was performed after 5 h of detorsion in the early orchiectomy model (EOM). In the late orchiectomy model (LOM), the ischemia period was 5 It and orchiectomy was performed after 7 days of detorsion. In the EOM, ibuprofen (70 mg/kg, po) was administrated only once, 40 min prior to detorsion. In the LOM, ibuprofen (70 mg/kg, po) was administered 40 min before detorsion, once daily for 7 days. Bilateral orchiectomy was performed in all groups to measure the tissue levels of malondialdehyde (MDA) and to microscopically investigate, light and electrons. The presence of endothelial nitric oxide synthase (eNOS) activity was shown with immunohistochemical studies. Spermatogenesis and mean seminiferous tubule diameter (MSTD) were significantly decreased in ipsilateral and contralateral testis when both early band late I/R groups were compared to the sham groups. Furthermore, ibuprofentreated animals showed an improved histological appearance in both models of testicular torsion. lbuprofen treatment prevented lipid peroxidation resulting in decreased MDA accumulation in the testes of both models. After I/R, eNOS immunoreactivity was increased in the testicular tissues. lbuprofen treatment decreased eNOS immunoreactivity in the germ cells of the tubules in the contralateral testes, but intense eNOS immunoreactivity was shown in the ipsilateral testes of the LOM. Electron microscopy of the testes of rats demonstrated that ibuprofen pretreatment was particularly effective in preventing the mitochondrial degeneration in both Sertoli and spermatid cells in the LOM. Because of its anti -inflammatory and antioxidant effects, ibuprofen pretreatment may have protective effects in the experimental testicular torsion/detorsion model in rats.Öğe Protective effects of L-carnitine and alpha-lipoic acid in rats with adjuvant arthritis(Academic Press Ltd- Elsevier Science Ltd, 2007) Tastekin, Nurettin; Aydogdu, Nurettin; Dokmeci, Dikmen; Usta, Ufuk; Birtane, Murat; Erbas, Hakain; Ture, MevlutFree radicals play an important role in the pathophysiology of adjuvant arthritis. The purpose of this study was to assess the efficacy Of L-carnitine (LC) and alpha-lipoic acid (alpha-LA) which are known to have antioxidant effects, in the treatment of adjuvant arthritis. Arthritis model was created by the administration of complete Freund's adjuvant (CFA) in 32 of 40 male Sprague-Dawley rats. The rats were divided into five groups. Rats in Group I served as controls and received 0.1 ml kg(-1) saline. Group II received only 0.1 ml of CFA and served as the CFA-control for the other groups. Groups III-V, after being injected with CFA, were treated with LC, alpha-LA or diclofenac, respectively. Levels of malondialdehyde (MDA) and glutathione (GSH) were measured in plasma samples. Enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. The paws of rats were evaluated histopathologically to investigate the anti-inflammatory effects. TNF-alpha levels were measured for the evaluation of inflammation. In G roup II plasma MDA increased, levels of glutathione decreased, enzymeactivities of SOD and GPx decreased. Histopathological damage increased in the paws of the rats in this group. MDA levels decreased in Groups III-V when compared with Group II. GSH levels significantly increased in Group III and IV than Group V. SOD activity of Group IV was higher than Group III and V. TNF-alpha levels were significantly lower in Group IV and V. LC and a-LA seemed to have protective effects against oxidative damage in adjuvant arthritis model. (c) 2007 Elsevier Ltd. All rights reserved.Öğe The Role of Hydrogen Sulfide in the Development of Tolerance and Dependence to Morphine in Mice(Karger, 2021) Cetin, Zeynep; Gunduz, Ozgur; Topuz, Ruhan D.; Dokmeci, Dikmen; Karadag, Hakan C.; Ulugol, AhmetObjective: Hydrogen sulfide is an endogenous gaseous mediator that has been indicated to have a role in pain mechanisms. In this study, we aimed to detect brain and spinal cord hydrogen sulfide levels during different phases of tolerance and dependence to morphine and to determine the effects of inhibition of endogenous hydrogen sulfide production on the development of tolerance and dependence. Methods: Morphine tolerance and dependence was developed by subcutaneous injection of morphine (10 mg/kg) twice daily for 12 days. Physical dependence was determined by counting the jumps for 20 min, which is a withdrawal symptom occurring after a single dose of naloxone (5 mg/kg) administered intraperitoneally (i.p.). Propargylglycine (30 mg/kg, i.p.), a cystathionine-gamma-lyase inhibitor, and hydroxylamine (12.5 mg/kg, i.p.), a cystathionine-beta-synthase inhibitor, were used as hydrogen sulfide synthase inhibitors. The tail-flick and hot-plate tests were used to determine the loss of antinociceptive effects of morphine and development of tolerance. Results: It was found that chronic and acute uses of both propargylglycine and hydroxylamine prevented the development of tolerance to morphine, whereas they had no effect on morphine dependence. Chronic and acute administrations of hydrogen sulfide synthase inhibitors did not exert any difference in hydrogen sulfide levels in brain and spinal cords of both morphine-tolerant and -dependent animals. Conclusion: It has been concluded that hydrogen sulfide synthase inhibitors may have utility in preventing morphine tolerance.Öğe Rosiglitazone, an agonist of peroxisome proliferator-activated receptor-gamma, prevents contralateral testicular ischaemia-reperfusion injury in prepubertal rats(Blackwell Publishing, 2007) Inan, Mustafa; Basaran, Umit; Dokmeci, Dikmen; Kanter, Mehmet; Yalcin, Omer; Aydogdu, Nurettin; Turan, Nesrin1. Rosiglitazone plays a positive role in the reparation of ischaemia-reperfusion (I/R) injury in different tissues. Thus, we examined its biochemical and histological effects on the contralateral testes to determine whether exogenous rosiglitazone affords any protection against testicular damage. 2. Forty-eight prepubertal male Wistar-Albino rats were divided into six groups. Testicular torsion was created by rotating the right testis 720 degrees in a clockwise direction for 5 h in all groups except group I, which was the sham-control group. In group II, bilateral orchiectomy was performed following the torsion period. After detorsion both testes were removed in the fifth hour in group III and on the seventh day in group IV. In group V, one-shot rosiglitazone (4 mg/kg) was administered 40 min before detorsion and both testes were removed following the torsion period. In group VI, rosiglitazone was administered (4 mg/kg) 40 min before detorsion and for 7 days, and then both testes were harvested. The tissue levels of malondialdehyde (MDA) were measured and mean testicular biopsy score (MTBS) and mean seminiferous tubule diameter (MSTD) were examined. Immunoexpression of endothelial nitric oxide synthase (eNOS) in testes tissues was investigated by immunohistochemical studies. 3. In the contralateral testis, the MTBS and MSTD values of group VI were significantly higher than those in group IV. Immunohistochemically, mild eNOS immunostaining was present in the germ cells of the contralateral testes in group IV after I/R. In group VI, intense eNOS immunoreactivity was seen in the contralateral testes. 4. Rosiglitazone reduces contralateral testicular damage formed after unilateral testicular torsion and alleviates the oxidative events.
