Meral Keyer-Uysal

Marmara University, İstanbul, Istanbul, Turkey

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Publications (14)32.62 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: In this study, the effects of melatonin or beta-glucan treatments on tumor growth, pro-oxidant, and antioxidant status in tumor tissue were investigated in Dunning 3327 MatLyLu prostatic adenocarcinoma model. Prostate cancer (PCa) was induced by single intradermal injection of 2 x 10(4) MatLyLu cells into the right hind leg of Copenhagen rats. Melatonin (10 mg/kg/daily; IP) or beta-glucan (50 mg/kg/daily; orally) treatments applied alone and together continued for 39 days. Melatonin or beta-glucan treatments alone or together inhibited tumor growth and decreased malondialdehyde (MDA) levels in tumor tissues of Dunning rats. However, there were no significant differences in tumor volumes and MDA levels among treatment groups. Melatonin and melatonin + beta-glucan treatments elevated glutathione (GSH) levels and superoxide dismutase, glutathione peroxidase, and glutathione transferase activities in tumor tissues. However, beta-glucan treatment did not influence GSH levels and antioxidant enzyme activities in tumor tissue of Dunning rats. These results indicate that melatonin and beta-glucan treatments alone or together inhibit tumor progression and oxidative stress in tumor tissues of rats with Dunning PCa.
    Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 01/2011; 19(6):259-63. · 1.63 Impact Factor
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    ABSTRACT: Objective: In the present study, we investigated the putative protective effect of melatonin and amlodipine against ischemia/reperfusion (I/R)-induced brain damage. Material and Methods: Wistar albino rats were subjected to 15 min of bilateral carotid artery occlusion followed by 24 h of reperfusion. Melatonin and amlodipine were administered in doses of either 10mg/kg ip or 50µg/rat icv just before reperfusion. After neurological examination the rats were decapitated. In the brain tissue samples, malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) and Na+-K+-ATPase activities, and luminol lucigenin chemiluminescence (CL) were determined. Brain edema was evaluated by the wet-dry weight method, and blood brain barrier (BBB) permeability was evaluated by the Evans Blue (EB) extravasation. Results: The neurological deficit was significantly improved in the melatonin and amlodipine groups when compared with the vehicle-treated groups. Ischemia/reperfusion caused a significant decrease in the brain GSH and Na+-K+-ATPase activity, which was accompanied with significant increases in the MDA level, MPO activity, and CL levels of the brain tissues. On the other hand, both melatonin and amlodipine treatment reversed all these biochemical indices as well as brain water content alterations induced by I/R. Conclusion: These findings suggest that both melatonin and amlodipine effectively modulate neuro-behavioural and neurochemical changes in global ischemia, most probably by virtue of their antioxidant properties. Keywords: melatonin; amlodipine; brain; ischemia / reperfusion, lipid peroxidation
    Marmara Medical Journal 01/2009; 22:34-44.
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    ABSTRACT: Sepsis is associated with enhanced generation of reactive oxygen species, which leads to multiple organ dysfunctions. Based on the potent antioxidant effects of silymarin, we investigated the putative protective role of silymarin against sepsis-induced oxidative damage in lung and brain tissues. Sepsis was induced by cecal ligation and perforation (CLP). Sham and CLP groups received either vehicle or silymarin (50 mg/kg, p.o.) or 150 mg/kg i.p. N-acetylcysteine (NAC) for 10 days prior and immediately after the operation. Six hours after the surgery, rats were decapitated and blood was collected for the measurement of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta [IL-1 beta], and IL-6) levels, lactate dehydrogenase activity, and total antioxidant capacity. Lung and brain samples were taken for the measurement of malondialdehyde and glutathione levels, myeloperoxidase activity, thromboplastic activity, and also for histological assessment. Formation of reactive oxygen species in tissue samples was monitored by using chemiluminescence technique with luminol and lusigenin probe. Sepsis increased serum TNF-alpha, IL-1 beta, IL-6 levels, and lactate dehydrogenase activity and decreased total antioxidant capacity. On the other hand, tissue glutathione levels were decreased while malondialdehyde levels and myeloperoxidase activity were increased in both the lung and the brain tissues due to CLP. Furthermore, luminol and lucigenin chemiluminescence were significantly increased in the CLP group, indicating the presence of the oxidative damage. Silymarine and NAC treatment reversed these biochemical parameters and preserved tissue morphology as evidenced by histological evaluation. Silymarin, like NAC, reduced sepsis-induced remote organ injury, at least in part, through its ability to balance oxidant-antioxidant status, to inhibit neutrophil infiltration, and to regulate the release of inflammatory mediators.
    Journal of Surgical Research 05/2008; 145(2):214-22. · 2.02 Impact Factor
  • Journal of Surgery Research. 01/2008; 145(2):214-22.
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    ABSTRACT: The aim of this study was to assess the antioxidant and antifibrotic effects of chronic administration of aqueous garlic extract on liver fibrosis induced by biliary obstruction in rats. Liver fibrosis was induced in male Wistar albino rats by bile duct ligation and scission (BDL). Aqueous garlic extract (AGE, 1 ml/kg, i.p., corresponding to 250 mg/kg) or saline was administered for 28 days. At the end of the experiment, rats were killed by decapitation. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were determined to assess liver functions and tissue damage, respectively. Tumor necrosis factor-alpha (TNF-alpha) was also assayed in serum samples. Liver tissues were taken for determination of the free radicals, renal malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Hepatic collagen content, as a fibrosis marker was also determined. Serum AST, ALT, LDH, and TNF- alpha levels were elevated in the BDL group as compared to control group, while this increase was significantly decreased by AGE treatment. Hepatic GSH levels, significantly depressed by BDL, were elevated back to control levels in AGE-treated BDL group. Increases in tissue free radical and MDA levels and MPO activity due to BDL were reduced back to control levels by AGE treatment. Similarly, increased hepatic collagen content in the BDL rats was reduced to the level of the control group with AGE treatment. Since AGE administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic structure and function, it seems likely that AGE with its antioxidant and antifibrotic properties, may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction.
    Life Sciences 05/2005; 76(22):2593-606. · 2.56 Impact Factor
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    ABSTRACT: We examined the effect of melatonin in prooxidant and antioxidant state in the liver of C57BL/6J mice fed on a high cholesterol (HC) diet. Mice were fed with normal mice chow containing 1.5% cholesterol and 0.5% cholic acid for 4 months without and with melatonin (10 mg/L in drinking water) treatment. HC diet was observed to increase malondialdehyde (MDA) and diene conjugate (DC) levels in the liver. This diet lowered glutathione (GSH), alpha-tocopherol, and total ascorbic acid levels as well as glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities in the liver, but hepatic superoxide dismutase (SOD) activity remained unchanged. Although melatonin treatment did not affect these parameters in mice fed a normal diet, it reduced hepatic MDA and DC levels in mice fed an HC diet. Hepatic alpha-tocopherol and ascorbic acid levels increased, but hepatic GSH levels remained unchanged in the melatonin-treated HC group as compared to the HC group. Melatonin treatment was found to increase liver GSH-Px and GST activities in mice fed an HC diet. However, SOD activity did not alter in the liver of hypercholesterolemic mice following melatonin treatment. In addition, the histopathological lesions observed in the cholesterol-plus-melatonin group were less severe than those seen in the cholesterol group. According to these observations, we can say that melatonin treatment has an ameliorating effect on the disturbances in prooxidant and antioxidant balance and histopathological lesions in the liver of mice following cholesterol feeding.
    International Journal for Vitamin and Nutrition Research 10/2004; 74(5):349-54. · 1.27 Impact Factor
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    ABSTRACT: We examined the hypolipidemic and antioxidative effects of melatonin in plasma, liver and aorta of C57BL/6J mice fed on a high cholesterol (HC) diet. Mice were fed normal mice chow containing 1.5% cholesterol and 0.5% cholic acid for 4 months with or without melatonin (10 mg/L in drinking water) treatment. HC diet was observed to increase cholesterol, triglyceride and diene conjugate (DC) levels in plasma and liver. There was a tendency towards an increase in cholesterol level in the aorta following HC diet. In addition, aortic DC levels were higher than those of control group. No fatty streaks or plaques developed in the aorta of mice following HC diet, but in some sections, derangement of the endothelial layer was detected. Melatonin treatment was found to reduce plasma, liver cholesterol and DC levels as well as liver triglyceride levels in hypercholesterolemic mice. Aortic cholesterol and DC levels were also reduced in hypercholesterolemic mice when given melatonin, although not statistically significant. There were no differences in aortic histopathological findings of mice fed on a HC diet with and without melatonin treatment. In conclusion, our results indicate that melatonin reduces HC diet-induced cholesterol accumulation and prooxidant state in the plasma, liver and probably in the aorta.
    Journal of Pineal Research 05/2004; 36(3):212-6. · 7.30 Impact Factor
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    ABSTRACT: The aims of this study are to encapsulate two different plasmid DNAs (pGL2 and pMK3) in the same microsphere structure and to investigate in vivo transfection characteristics of chitosan microspheres. Furthermore, the effect of formulation factors, such as chitosan concentration and plasmid DNA amount on in vitro properties of microspheres were studied. Double plasmid-loaded chitosan microspheres were prepared by complex coacervation. Release studies were done in phosphate buffered saline at 37 degrees C and released plasmid DNA was determined spectrophotometrically. Integrity of plasmid DNAs was checked by agarose gel electrophoresis. For in vivo transfection studies, microspheres were injected into the muscle of the mice and expression of proteins (beta-galactosidase and luciferase) was measured. High encapsulation efficiency was obtained with chitosan microspheres (90%). The size of particles was about 1.15 - 1.28 m. No dependence was observed between the size and formulation variables (chitosan concentration and the amount of plasmid). After encapsulation process, integrity of two plasmids did not change. Plasmid DNAs were continuously released from chitosan microspheres. Chitosan concentrations and plasmid amounts affected in vitro release properties. After intramuscular injection of double plasmids loaded microspheres into muscle of the mice, co-expression was obtained. High beta-galactosidase and luciferase productions were determined with these microspheres after a long post-transfection period (12 weeks). Our results showed that two plasmids could be encapsulated in chitosan microspheres without affecting their structural and functional integrity. Thus, sustained and high protein production was obtained with these microspheres.
    Journal of Pharmacy and Pharmaceutical Sciences 01/2003; 6(1):27-32. · 2.20 Impact Factor
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    ABSTRACT: Animal models of burn injury indicate oxygen radicals as causative agents in the local wound response, as well as in the development of burn shock and distant organ injury. This study was designed to determine the possible protective effect of melatonin treatment against oxidative damage in the liver, lung and intestine induced by burn injury. Under ether anaesthesia, the shaved dorsum of rats was exposed to a 90 degrees C bath for 10s to induce burn injury. Rats were decapitated either 3 or 24h after burn injury. Melatonin was administered i.p. immediately after burn injury. In the 24h burn group, melatonin injections were repeated for two more occasions. In the sham group the same protocol was applied except that the dorsum was dipped in a 25 degrees C water bath for 10s. Liver, lung and intestine tissues were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and protein oxidation (PO). Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, significant increases in MDA and PO levels, and MPO activity at postburn 3 and 24h. Treatment of rats with melatonin (10mg/kg) significantly elevated the reduced GSH levels while it decreased MDA and PO levels as well as MPO activity.
    Burns 09/2002; 28(5):419-25. · 1.80 Impact Factor
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    ABSTRACT: Animal models of thermal trauma implicate oxygen radicals as causative agents in local wound response and distant organ injury following burn. This study was designed to determine the effect of melatonin treatment on levels of glutathione (GSH), malondialdehyde (MDA), protein oxidation (PO) and myeloperoxidase (MPO) activity in the kidney tissues of rats with thermal injury. Under ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C bath for 10 s to induce burn injury. Rats were decapitated either 3 h or 24 h after burn injury. Melatonin was administered i.p. immediately after burn injury. In the 24-h burn group melatonin injections were repeated for two more occasions. In the sham group the same protocol was applied except that the dorsum was dipped in a 25 degrees C water bath for 10 s. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, and significant increases in MDA and PO levels, and MPO activity at post-burn 3 and 24 hours. Treatment of rats with melatonin (10 mg/kg) significantly elevated the reduced GSH levels while it decreased MDA and PO levels as well as MPO activity.
    Life Sciences 06/2002; 70(25):2977-85. · 2.56 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Animal models of thermal trauma implicate oxygen radicals as causative agents in local wound response and distant organ injury following burn . This study was designed to determine the effect of melatonin treatment on levels of glutathione (GSH), malondialdehyde (MDA), protein oxidation (PO) and myeloperoxidase (MPO) activity in the kidney tissues of rats with thermal injury. Under ether anaesthesia, shaved dorsum of the rats was exposed to 90 °C bath for 10 s to induce burn injury. Rats were decapitated either 3 h or 24 h after burn injury. Melatonin was administered i.p. immediately after burn injury. In the 24-h burn group melatonin injections were repeated for two more occasions. In the sham group the same protocol was applied except that the dorsum was dipped in a 25 °C water bath for 10 s. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, and significant increases in MDA and PO levels, and MPO activity at post-burn 3 and 24 hours. Treatment of rats with melatonin (10 mg/kg) significantly elevated the reduced GSH levels while it decreased MDA and PO levels as well as MPO activity.
    Life Sciences. 05/2002;
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    ABSTRACT: Oxygen free radicals are considered to be important components involved in the pathophysiological tissue alterations observed during ischemia-reperfusion (I/R). In this study, we investigated the putative protective effects of melatonin treatment on renal I/R injury. Wistar albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 1, 3, 6, 24, 48 hr or 1 wk of reperfusion. Melatonin (10 mg/kg, s.c.) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion periods, rats were decapitated. Kidney samples were taken for histological examination or the determination of renal malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and protein oxidation (PO). Serum creatinine and blood urea nitrogen (BUN) concentrations were measured for the evaluation of renal function. The results revealed that I/R induced nephrotoxicity, as evidenced by increases in BUN and creatinine levels at each time point, was reversed by melatonin treatment. The decrease in GSH and increases in MDA, MPO and PO induced by I/R indicated that renal injury involves free radical formation. As melatonin administration reversed these oxidant responses, improved renal function and microscopic damage, it seems likely that melatonin protects kidney tissue against oxidative damage.
    Journal of Pineal Research 04/2002; 32(2):120-6. · 7.30 Impact Factor
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    ABSTRACT: The small intestine is highly sensitive to oxygen free radical-induced injury. Post-ischemic intestinal tissue damage appears to be due to the formation of oxygen radicals. Free radical initiated lipid peroxidation (LP) following intestinal ischemia/reperfusion (I/R) may disrupt mucosal integrity. Indirectly, the radicals trigger the accumulation of neutrophils within the affected tissue, initiating inflammatory processes that lead to severe mucosal lesions. In the present study we investigated the effect of pentoxifylline (PTX), a potent inhibitor of tumour necrosis factor production, on I/R induced intestinal injury. Wistar albino rats were divided into four groups: (1) Sham operation (S); (2) Sham operation + PTX (50 mg/kg i.v.) (S + PTX); (3) 1 h ischemia + 2 h reperfusion (I/R); and (4) I/R + PTX. Animals were sacrificed at the end of the reperfusion period and ileum samples were obtained. Malondialdehyde (MDA) levels, an end product of LP, glutathione (GSH) levels, a key antioxidant, and myeloperoxidase (MPO) activity (an index of polymorphonuclear neutrophils) stimulation, were determined in ileum homogenates. The results of the present study indicate that ischemia/reperfusion results in a significant increase in MDA content and MPO activity with a significant decrease in GSH content. Treatment with PTX returns these biomarkers to control values. A mechanism of this protective effect may involve inhibition of neutrophil oxidative burst.
    Fundamental and Clinical Pharmacology 03/2001; 15(1):19-22. · 1.99 Impact Factor
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    ABSTRACT: Abstract— Regarding the mechanisms of cisplatin (CP) nephrotoxicity, several hypotheses have been put forward, among which oxidative stress (including depletion of glutathione and production of lipid peroxide) is noticeable. This investigation elucidates the role of the antioxidant system in CP-induced nephrotoxicity and the nephroprotection by melatonin. Balb/c mice were injected i.p. with: 1) vehicle control; 2) a single dose of 6.5 mg/kg cisplatin, CP group; 3) melatonin in a dose of 10 mg/kg for 5 days after CP injection, CP-M group; 4) melatonin (10 mg/kg) for 5 days before and after CP injection, M-CP-M group; 5) melatonin in a dose of 10 mg/kg for 5 days, M group. Mice were sacrificed 5 days after CP injection to determine blood urea nitrogen (BUN) and serum creatinine. Renal lipid peroxidation (LP) and glutathione (GSH) levels were evaluated in kidney homogenates. Cisplatin administration resulted in increased LP, BUN and serum creatinine levels and decreased GSH levels, whereas melatonin reversed these effects. Morphological kidney damage was apparent in the CP group. Mentioned degeneration was moderate in the CP-M group, whereas morphological findings of the M-CP-M group implied a well preserved kidney tissue. When M was administered alone, it didn't cause any significant change in biochemical parameters. Both C and M groups exhibited similar biochemical and morphological findings in light and transmission electron microscope observation. In conclusion, the present study suggests that melatonin may be of therapeutic benefit when used with CP.
    Fundamental and Clinical Pharmacology 11/2000; 14(6):553 - 560. · 1.99 Impact Factor

Publication Stats

175 Citations
32 Downloads
662 Views
32.62 Total Impact Points

Institutions

  • 2000–2011
    • Marmara University
      • • Faculty of Pharmacy
      • • Department of Pharmacology
      • • Department of Medical Pharmacology
      İstanbul, Istanbul, Turkey
  • 2009
    • İstanbul Bilgi Üniversitesi
      İstanbul, Istanbul, Turkey
  • 2004
    • Istanbul University
      • Department of Family Medicine (Istanbul Medical Faculty)
      İstanbul, Istanbul, Turkey