Browsing by Author "Savic-Radojevic, A. (16246037100)"

Despite evidence that essential hypertension (EH) is a state of increased oxidative stress, the data on oxidative protein modifications is lacking. Besides, the role of extracellular antioxidant enzymes in EH has not been systematically studied. Study was performed in 45 subjects with EH and 25 normotensive controls. Patients were divided into three groups according to the 2003 ESH/ESC guidelines (grade 1-3). Plasma protein reactive carbonyl derivatives (RCD) and SH-groups (as byproducts of oxidative protein damage) as well as antioxidant enzyme activities superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase were studied spectrophotometrically and correlated with blood pressure (BP). RCD levels were increased in EH patients compared to controls and correlated significantly with both systolic blood pressure (SBP) (r = 0.495, P<0.01) and diastolic blood pressure (DBP) (r = 0.534, P<0.01). Plasma SH-groups content was significantly lower in all patients with EH, with no correlation with BP. SOD and catalase activity in patients with grade 1 EH were similar to that of controls. Patients with grade 2 and 3 of EH had lower SOD and catalase activity. However, significant correlation with SBP and DBP was observed for catalase only (r=0.331; P<0.05 and r=22;0.365; P<0.05, respectively). EH patients exhibited higher plasma GPX activity compared to those in controls, and it correlated with SBP (r = 0.328; P<0.05). The results presented show that increased oxidative protein damage is present in all grades of EH. In mild hypertension extracellular antioxidant enzyme activities are not decreased, suggesting they are probably not critical in early EH, but could be important in moderate to severe EH. © 2006 Nature Publishing Group All rights reserved.

Objectives. To perform a systematic functional investigation of different glutathione S-transferase (GST) classes, including GST class Theta (GSTT) member GSTT1-1, in transitional cell carcinoma (TCC) and the surrounding normal uroepithelium of the same individuals. Recently, it was suggested that GSTT1-1 might be an important risk modulator for TCC. Methods. Tumor samples and surrounding normal uroepithelium were obtained from 24 patients with TCC of urinary bladder. The following substrates with differential specificities were used: 1-chloro-2,4-dinitrobenzene for overall GST activity; 7-chloro-4- nitrobenzo-2-oxa-1,3-diazole for GST Alpha; 1,2-dichloro-4-nitro-benzene for GST Mu; 4-vinylpyridine for GST Pi 1-1(GSTP1-1); and 1,2-epoxy-3-(p-nitrophenoxy) propane for GSTT1-1. Results. GSTP1-1 and GSTT1-1 activities were demonstrated in all uroepithelial and TCC samples, and GST Mu activity was detectable in 11 of 24 patients. In the tumor specimens, significant upregulation of all expressed GST subtypes was observed. The mean GSTP1-1 and GSTT1-1 level in TCC was increased 2-fold and 3.6-fold, respectively, compared with the mean level in the normal uroepithelium (P <0.001). Tumor GSTT1-1 activities correlated statistically significantly with the tumor stage (P <0.05). Conclusions. In tumors and adjacent normal uroepithelium of patients with TCC, three major cytosolic GST classes, Mu, Pi, and Theta, were expressed. Although the GST isoenzyme pattern in TCC was similar to that of the corresponding normal uroepithelium, during cancer progression a clear tendency toward an increase in all the GST subtypes expressed was noted. For the first time, distinct GSTT1-1 activity levels were demonstrated in human uroepithelium, as well as its pronounced upregulation in TCC. © 2005 Elsevier Inc.

To get more insight into molecular mechanisms underlying oxidative stress and its link with insulin resistance, oxidative stress parameters, as well as, antioxidant enzyme activities were studied in young, non-obese women with polycystic ovary syndrome (PCOS). Study was performed in 34 PCOS women and 23 age and body mass index (BMI)-matched healthy controls. Plasma nitrotyrosine and malondialdehyde (MDA), representative byproducts of protein and lipid oxidative damage, were determined by enzyme immunoassay. Antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPX) were studied spectrophotometrically. Insulin resistance was calculated using homeostasis assessment model (HOMA-IR). Plasma nitrotyrosine and MDA were increased, but only nitrotyrosine was signifi cantly higher (p < 0.05) in PCOS women compared to controls. Uric acid (surrogate marker of × antine oxidase) was also signifi cantly elevated in PCOS (p < 0.05). Both plasma SOD and GPX activity showed no statistically significant difference between PCOS and controls. Indices of insulin resistance (insulin and HOMAIR) were significantly higher in PCOS group and positively correlated with level of MDA (r = 0.397 and r = 0.523, respectively; p < 0.05) as well as GPX activity (r = 0.531 and r = 0.358, respectively; p < 0.05). Our results indicate that insulin resistance could be responsible for the existence of subtle form of oxidative stress in young, nonobese PCOS women. Hence, presence of insulin resistance, hyperinsulinemia and oxidative damage are likely to accelerate slow development of cardiovascular disease in PCOS. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

To get more insight into molecular mechanisms underlying oxidative stress and its link with insulin resistance, oxidative stress parameters, as well as, antioxidant enzyme activities were studied in young, non-obese women with polycystic ovary syndrome (PCOS). Study was performed in 34 PCOS women and 23 age and body mass index (BMI)-matched healthy controls. Plasma nitrotyrosine and malondialdehyde (MDA), representative byproducts of protein and lipid oxidative damage, were determined by enzyme immunoassay. Antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPX) were studied spectrophotometrically. Insulin resistance was calculated using homeostasis assessment model (HOMA-IR). Plasma nitrotyrosine and MDA were increased, but only nitrotyrosine was signifi cantly higher (p < 0.05) in PCOS women compared to controls. Uric acid (surrogate marker of × antine oxidase) was also signifi cantly elevated in PCOS (p < 0.05). Both plasma SOD and GPX activity showed no statistically significant difference between PCOS and controls. Indices of insulin resistance (insulin and HOMAIR) were significantly higher in PCOS group and positively correlated with level of MDA (r = 0.397 and r = 0.523, respectively; p < 0.05) as well as GPX activity (r = 0.531 and r = 0.358, respectively; p < 0.05). Our results indicate that insulin resistance could be responsible for the existence of subtle form of oxidative stress in young, nonobese PCOS women. Hence, presence of insulin resistance, hyperinsulinemia and oxidative damage are likely to accelerate slow development of cardiovascular disease in PCOS. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Novel glutathione S-transferase (GST) isoenzymes, which do not bind to the glutathione (GSH) affinity column, were recently identified in dog kidney and dog renal cell lines. In humans, similar affinity flow-through GST has been previously found only in the urinary bladder. To ascertain whether these affinity flow-through GST isoenzymes also exist in the human kidney, we separated GST isoenzymes from five kidney samples on the basis of their affinity to GSH affinity resin. GSTs were further purified by anion exchange chromatography and chromatofocusing and characterized with specific substrates. Our results show that the human kidney has both affinity flow-through GST isoenzymes and those which bind tightly to the GSH affinity column. Purification of affinity-bound GST resulted in a rich profile of different isoenzymes with balanced expression of both anionic and cationic forms. Affinity flow-through GST was represented by one isoenzyme (pI-7.9) in all kidney samples tested, but one kidney specimen also contained another GST isoenzyme (pI-7.0). Our results for the first time show the presence of GST isoenzymes that do not bind to GSH-affinity resin in the human kidney. Although the assessment of similarity between the human kidney and urinary bladder affinity flow-through GST requires further elucidation, it can be speculated that these particular GSTs may play an important role in providing protection against the common carcinogens.