Meral Keyer-Uysal

Marmara University, İstanbul, Istanbul, Turkey

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Publications (18)39.85 Total impact

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    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.
    No preview · Article · Jun 2011 · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics
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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
    Full-text · Article · Jan 2009 · Marmara Medical Journal
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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.
    Full-text · Article · May 2008 · Journal of Surgical Research

  • No preview · Article · Jan 2008
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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.
    No preview · Article · May 2005 · Life Sciences
  • Jale Balkan · Göksel Sener · Uğur Cevikbaş · Meral Keyer-Uysal · Müjdat Uysal
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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.
    No preview · Article · Oct 2004 · International Journal for Vitamin and Nutrition Research
  • Göksel Sener · Jale Balkan · Ugur Cevikbaş · Meral Keyer-Uysal · Müjdat Uysal
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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.
    No preview · Article · May 2004 · Journal of Pineal Research
  • J. Akbuga · C. Aral · S. Özbas-Turan · L. Kabasakal · M. Keyer-Uysal
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    ABSTRACT: This study investigates the effect of the topology of the encapsulated plasmid DNA on its in vitro transfection efficiency, using two different plasmids [large pMK3 (7.2 kb) and small pUC18 (2.69 kb)]. DNA-chitosan microspheres containing a mixture of a supercoiled (sc) and an open circular (oc) form, of a linear form, were prepared using a complex coacervation process. Microsphere properties such as size and in vitro release pattern were evaluated. Topology of the plasmid DNA was assessed by using agarose gel electrophoresis. The mean size of the microspheres was about 3.4-3.7 μm. The in vitro release of plasmid DNA from chitosan microspheres indicated a sustained release characteristic. For the in vitro transfection study, the mouse fibroblast cell line (L-strain) was used. Transfection of encapsulated sc + oc forms mixture and linearised form were compared, the results showed that an encapsulated sc + oc mixture has higher level β-galactosidase expression. For the in vivo transfection study, free and encapsulated forms were injected into the anterior tibialis muscle of the rats. At time intervals, biopsies were performed and β-galactosidase activity was measured spectrophotometrically using ONPG (o-nitrophenyl-β-D-galactopyranoside) as a substrate. Chitosan microspheres prepared with the mixture of supercoiled and open circular forms showed a higher β-galactosidase expression and the proportion of supercoiled to open circular forms in the mixture had no effect on the transfection efficiency of chitosan microspheres. The importance of plasmid DNA size was not clear in these experiments because similar transfection data were obtained with two different sizes of plasmids.
    No preview · Article · Mar 2003 · S.T.P. Pharma Sciences
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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.
    Full-text · Article · Jan 2003 · Journal of Pharmacy and Pharmaceutical Sciences
  • G. Şener · M. Keyer-Uysal · H. Neşe Doǧan · S. Rollas
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    ABSTRACT: The aim of the study was to investigate the antioxidant effect of 2-(3-acetyloxy-2-naphthyl)-4-acetyl-5-phenyl-1,3,4-oxadiazoline (OXA) in mice brain and liver. In this study we also compared the antioxidant and anticonvulsive effets of OXA with that of valproat (VPA), an antiepileptic drug. OXA (100 mg.kg-1) and valproat (150 mg.kg-1) were administered i.p. to mice 4 hours and 1 hour respectively prior pentylenetetrazol (PTZ) injection. Animals were sacrificed after tonic and clonic convulsion and brain and liver tissues were immediately removed to analyse for lipid peroxidation (LPO) and glutathione (GSH) levels. Both OXA and VPA significantly decreased LPO levels in brain and liver which were elevated after PTZ administration. PTZ administration caused depletion of GSH in both brain and liver, however OXA and VPA treatment reversed the GSH levels to control. The results indicated that OXA and VPA protected brain and liver tissue against oxidative damage seen at the time of seizures.
    No preview · Article · Jan 2003 · Acta Pharmaceutica Turcica
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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.
    No preview · Article · Sep 2002 · Burns
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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.
    No preview · Article · Jun 2002 · Life Sciences
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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.
    No preview · Article · Apr 2002 · Journal of Pineal Research
  • G Sener · Akgün U · H Satiroğlu · U Topaloğlu · M Keyer-Uysal
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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.
    No preview · Article · Mar 2001 · Fundamental and Clinical Pharmacology
  • G. Şener · H. Şatiroglu · L. Kabasakal · S. Arbak · S. Öner · F. Ercan · M. Keyer-Uysal
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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.
    No preview · Article · Nov 2000 · Fundamental and Clinical Pharmacology
  • C. Aral · S. Özbas-Turan · L. Kabasakal · M. Keyer-Uysal · J. Akbuga
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    ABSTRACT: Gene therapy strategies depend on efficient devices for the delivery of nucleic acid into target cells. In this study, DNA-chitosan microspheres were investigated from a pharmaceutical standpoint and the effects of different factors such as plasmid size, chitosan concentration and plasmid addition techniques, on the characterization and in vivo transfection of microspheres were studied. Different doses of DNA-chitosan microspheres were also tested for their gene expression properties. Large and small plasmids (pMK3 and pUC18, respectively) were used to study the importance of plasmid size to in vitro DNA release and transfection properties. Naked and encapsulated plasmids were injected into the muscle of the rats and their β-galactosidase production was measured. According to our data, the effect of plasmid size and chitosan concentration on transfection efficacy was not clear. However, the DNA dose injected in rats was of importance to β-galactosidase production. The highest levels of β-galactosidase expression were obtained with low-dose DNA-chitosan microspheres. The injection of naked plasmid DNA to rats resulted in negligible expression. On the other hand, the structural and functional integrity of encapsulated plasmid DNA remained unchanged during the study.
    No preview · Article · Jan 2000 · S.T.P. Pharma Sciences
  • H.N. Dogan · A. Duran · S. Rollas · G. Sener · Y. Armutak · M. Keyer-Uysal
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    ABSTRACT: We have synthesized new compounds, which have the structures of 3-hydroxy-2-naphthoic acid (substitutedmethylene)-hydrazides and 2-(3-acetyloxy-2-naphthyl)-4-acetyl-5-substituted-1,3,4-oxadiazolines to establish their anticonvulsant activities. Twelve compounds were original. Hydrazones were obtained by condensation of 3-hydroxy-2-naphthoic acid hydrazide with appropriate aldehydes. Cyclization of the hydrazones in the presence of acetic anhydride gave oxadiazolines. The structures of these substances were confirmed their sharp melting points, elementary analysis, UV,1H-NMR and mass spectral methods. When evaluated for anticonvulsant activities in mice, the protection afforded by oxadiozolines against pentylenetetrazole-induced convulsions ranged from 0 to 60%.
    No preview · Article · Jan 1998
  • Müjdat Uysal · Meral Keyer-Uysal · Necla Koçak-Toker · Gülçin Aykaç
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    ABSTRACT: Rat liver and brain lipid peroxide and glutathione levels were determined after chronic ethanol treatment. Although hepatic lipid peroxidation was significantly stimulated, we have failed to observe any change in brain lipid peroxide and glutathione levels of rats chronically treated with ethanol.
    No preview · Article · Oct 1986 · Drug and Alcohol Dependence