Hilal Özgüneş

Antioxidant effects of N-acetylcysteine and succimer in red blood cells from lead-exposed rats

This study examined whether lead-induced alterations in selected parameters that are indicative of oxidative stress accompany the toxic effects of lead in red blood cells (RBCs) in vivo. It also explored the possibility that treatment with N-acetylcysteine (NAC) or succimer (meso-2,3-dimercaptosuccinic acid) was capable of reversing parameters indicative of lead-induced oxidative stress. Fisher 344 rats were given 2000 ppm lead acetate in their drinking water for 5 weeks. The lead was then removed and the animals were given NAC (800 mg/kg/day) or succimer (90 mg/kg/day) in their drinking water for 1 week, after which the RBCs were harvested. Animals not given lead and those given lead, but not NAC or succimer, served as negative and positive controls, respectively. At the end of the experiment, blood-lead levels were 35 +/- 4 microg/dl in lead-treated animals, which were reduced to 2.5 +/- 1 microg/dl by treatment with succimer and to 25 +/- 3 microg/dl by treatment with NAC. Lead-exposed animals demonstrated signs of anemia as evidenced by anisocytosis, poikilocytosis, and alterations in hemoglobin, hematocrit, and mean corpuscular volume. Lipid peroxidation, as evidenced by increased malondialdehyde (MDA) content, as well as decreases in reduced glutathione (GSH) and increases in catalase and glucose 6-phosphate dehydrogenase (G6PD) activity were noted in RBCs from lead-treated rats, suggesting that the lead induced oxidative stress. In addition, a significant reduction in blood delta-aminolevulinic acid dehydratase (ALAD) activity suggested that accumulation and autooxidation of delta-aminolevulinic acid might contribute to lead-induced oxidative stress. Treatment with either NAC or succimer reversed lead-induced alterations in MDA and GSH content, but only succimer appeared to partially restore ALAD activity. These results provide in vivo evidence supporting the hypothesis that lead induces oxidative stress in RBCs, which is reversible by treatment with a thiol antioxidant (NAC), as well as a chelating agent (succimer).

Antioxidant Role of α-lipoic Acid in Lead Toxicity

The assumption of oxidative stress as a mechanism in lead toxicity suggests that antioxidants might play a role in the treatment of lead poisoning. The present study was designed to investigate the efficacy of lipoic acid (LA) in rebalancing the increased prooxidant/antioxidant ratio in lead-exposed Chinese hamster ovary (CHO) cells and Fischer 344 rats. Furthermore, LAs ability to decrease lead levels in the blood and tissues of lead-treated rats was examined. LA administration resulted in a significant improvement in the thiol capacity of cells via increasing glutathione levels and reducing malondialdehyde levels in the lead-exposed cells and animals, indicating a strong antioxidant shift on lead-induced oxidative stress. Furthermore, administration of LA after lead treatment significantly decreased catalase and red blood cell glucose-6-phosphate dehydrogenase activity. In vitro administration of LA to cultures of CHO cells significantly increased cell survival, that was inhibited by lead treatment in a concentration- dependent manner. Administration of LA was not effective in decreasing blood or tissue lead levels compared to a well-known chelator, succimer, that was able to reduce them to control levels. Hence, LA seems to be a good candidate for therapeutic intervention of lead poisoning, in combination with a chelator, rather than as a sole agent.

Preventive effect of aminoguanidine compared to vitamin E and C on cisplatin-induced nephrotoxicity in rats.

In this study, the antioxidant effect of aminoguanidine on nephrotoxicity of a single dose of cisplatin is investigated and compared with the effects of well-known antioxidants vitamin C and E combination. Tubular damage and perivascular inflammation were observed in kidney samples of the cisplatin-administered groups. Aminoguanidine and vitamin C-E combination are found to be capable of preventing these effects of cisplatin. Liver tissues of all groups were intact. Cisplatin-induced oxidative stress was evidenced by significant decrease in glutathione and significant increase in malondialdehyde levels in kidney samples. Antioxidants with cisplatin decreased malondialdehyde levels. Antioxidants with cisplatin prevented the decrease in liver glutathione levels. The nephrotoxicity was confirmed biochemically by significant elevation of serum urea and creatinine levels. Both vitamin C-E combination and aminoguanidine prevented the increase in serum urea levels according to the cisplatin group.

Oxidative protein damage with carbonyl levels and nitrotyrosine expression after chemotherapy in bone marrow transplantation patients.

Protein oxidation is defined as the covalent modification of a protein, induced either directly by reactive oxygen species/reactive nitrogen species or indirectly by reaction with secondary by-products of oxidative stress. Protein carbonyls are the most commonly measured products of protein oxidation. Additionally, nitrotyrosine is a product of tyrosine nitration mediated by reactive nitrogen species such as peroxynitrite anion and nitrogen dioxide. Samples were collected before the preparative regimen (10 days before transplantation; day –10), on transplantation day (day 0), and after transplantation (days 7, 14, and 28) from 16 pediatric allogeneic hematopoietic stem cell transplantation (HSCT) patients. The erythrocyte 3-nitrotyrosine expression was shown to be significantly increased after chemotherapy. In accordance, the mean plasma carbonyl levels on days 14 and 28 were significantly higher than on the other days. High-dose chemotherapy applied in the preparative regimen of HSCT may be responsible for this long-term oxidation of plasma proteins. These results show that high-dose chemotherapy resulted in protein oxidation both in plasma and in erythrocytes in HSCT patients.

Serum and parotid saliva testosterone, calcium, magnesium, and zinc levels in males, with and without periodontitis

Fourteen male patients with periodontitis and 10 patients free of periodontitis were included in the study. The concentrations of testosterone (T), calcium (Ca), magnesium (Mg), and zinc (Zn) were measured in serum and parotid saliva. Patients with periodontitis had increased Ca and decreased Zn serum levels, and they had decreased Ca and increased T levels in parotid saliva. Furthermore, there was a low correlation between parotid saliva T and Mg levels in the patients with periodontitis (r=0.61,n=14,t=2.663,p<0.005), and there is an inverse relationship between serum and parotid saliva Mg levels (r=−0.58,n=14,t=2.468,p<0.05).

Serum protein and zinc levels in patients with thoracic empyema.

The element Zn is the metal component or activator of many important enzymes. The tissue concentrations and activities of Zn metalloenzymes direct the rate of protein and nucleic acid syntheses, thereby influencing tissue growth and reperative processes. Most of the serum Zn is normally bound to circulating proteins. Low serum Zn concentrations might result from depletion of Zn-binding proteins. Serum protein and Zn concentrations have been reported to be depressed in patients with acute and chronic diseases. We compare the serum protein and Zn values of patients with thoracic empyema (n=20) with those of a control group (n=20). The values obtained in the empyema group were significantly lower than those in the control group before the study. Test group administered 220 mg zinc sulfate (ZnSO4. 7H2O) over 20 d and there was a significant increase in the values for serum protein and Zn after the oral administration of the zinc sulfate.

Effect of bleaching on mercury release from amalgam fillings and antioxidant enzyme activities: a pilot study.

OBJECTIVE The aim of this pilot clinical study was to determine the mercury release from amalgam fillings and antioxidant enzyme activities (Superoxide Dismutase [SOD] and Catalase[CAT] ) in body fluids after exposure to two different vital tooth bleaching systems. MATERIAL AND METHODS Twenty eight subjects with an average age of 25.6 years (18-41) having at least two but not more than four Class II amalgam fillings on each quadrant arch in the mouth participated in the study. Baseline concentrations of mercury levels in whole blood, urine, and saliva were measured by a Vapor Generation Accessory connected to an Atomic Absorption Spectrometer. Erythrocyte enzymes, SOD, and CAT activities in blood were determined kinetically. Subjects were randomly assigned to two groups of 14 volunteers. Group 1 was treated with an at-home bleaching system (Opalescence PF 35% Carbamide Peroxide, Ultradent), and Group 2 was treated with a chemically activated office bleaching system (Opalescence Xtra Boost 38% Hydrogen Peroxide, Ultradent) according to the manufacturers recommendations. Twenty-four hours after bleaching treatments, concentrations of mercury and enzymes were remeasured. RESULTS There were no significant differences on mercury levels in blood, urine, and saliva before and after bleaching treatments (p > 0.05). No differences were also found in the level of antioxidant enzyme activities (SOD and CAT) before and after treatments (p > 0.05). Mercury release did not affect the enzyme activities (p > 0.05). CONCLUSION Bleaching treatments either office or home did not affect the amount of mercury released from amalgam fillings in blood, urine, and saliva and the antioxidant-enzyme activities in blood. CLINICAL SIGNIFICANCE Bleaching treatments with the systems tested in this pilot study have no deleterious effect on the mercury release from amalgam fillings and antioxidant enzymes in body fluids.

Antioxidant secondary metabolites from Geranium lasiopus Boiss. & Heldr.

Chromatographic studies on the EtOAc soluble portion of the MeOH extract of Geranium lasiopus led to the isolation of eight flavonoids (kaempferol (1), quercetin (2), quercetin 3-O-β-glucopyranoside (3), quercetin 3-O-β-galactopyranoside (4), kaempferol 3-O-α-rhamnopyranosyl-(1 → 6)-β-glucopyranoside (5), quercetin 3-O-α-rhamnopyranosyl-(1 → 6)-β-glucopyranoside (6), kaempferol 3-O-α-rhamnopyranosyl-(1 → 2)-β-glucopyranoside (7) and quercetin 3-O-α-rhamnopyranosyl-(1 → 2)-β-glucopyranoside (8)), two simple phenolic compounds (gallic acid (9) and its methyl ester (10)) and a hydrolysable tannin (pusilagin (11)). The structures of the compounds were elucidated by 1- and 2-dimensional NMR techniques (1H, 13C, COSY, HMBC, HMQC) and ESI-TOF-MS spectrometry. Inhibitory effects on H2O2-induced lipid peroxidation in human red blood cells of the different extracts of G. lasiopus, as well as isolated compounds, were investigated. All tested compounds showed comparable or higher activity than that of ascorbic acid and trolox.

Cofactor metals and antioxidant enzymes in cisplatin-treated rats: effect of antioxidant intervention.

Abstract We explored the association between the activities of antioxidant enzymes and their metallic cofactors in rats treated with cisplatin. The antioxidant effects of aminoguanidine, and a combination of vitamins E and C were investigated. Plasma platin was significantly lower than liver and kidney. Cisplatin treatment caused significant increase in plasma Se-glutathione peroxidase activity. Activities of Se-glutathione peroxidase, glutathione S-transferase, catalase and Cu,Zn-superoxide dismutase have been found to be significantly decreased in liver and kidney compared to controls. Zn levels in these organs were diminished upon cisplatin treatment, while levels of Cu were unaffected. Interestingly, levels of iron, the cofactor of catalase, were found to be significantly increased in liver and kidney. Intervention with aminoguanidine or vitamins was generally prevented cisplatin-caused changes in the activity of enzymes and in the tissue levels of cofactor metals. These observations suggest that relation between activities of enzymes and levels of cofactor metals is multifactorial.

SİSPLATİN TOKSİSİTESİ: OKSİDATİF STRESİN ÖNEMİ VE ANTİOKSİDANLARIN ETKİSİ

Sisplatin (CP) cesitli kanserlerin tedavisinde yaygin olarak kullanilan kematerapotik ajanlardan biridir, ancak, nefrotoksisisite, hepatotoksisite, ototoksisite gibi cesitli kullanimini kisitlayan yan etkilere sahiptir. Bazi calismalar, CP uygulamasi ile serbest radikal olusumunun ve dolayisiyla oksidatif hasarin arttigini gostermistir. Bu bulgular, oksidatif stresin CP toksisitesinde onemli bir rol oynadigina isaret etmektedir. Diger yandan, bircok calisma antioksidan ajanlarin CP toksisitesini onlenebilecegini gostermistir. Bu derlemede, CP toksisitesinde oksidatif stresin onemi ve antioksidanlar ile CP toksisitesinin onlenmesi ile ilgili calismalara yer verilmistir.