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The use of cisplatin in chemotherapy may provoke a deteriorating impact in many vital organs, suggesting the need for more selective derivatives and effective protective cotreatments. This study assesses the effects of three novel Pt(IV) complexes containing ethyl-, propyl- and butyl-esters of the ethylenediamine-N, N’-di-S, S- (2,2’-dibenzyl) acetic acid on liver injury markers, redox parameters, and cell morphology of female rat liver tissue in comparison to cisplatin. In addition, the study evaluates the possible protective effects of resveratrol as well. The rats were divided into ten groups and were administered intraperitoneally with a single dose of cisplatin (7.5 mg/kg) or Pt(IV) complexes (10 mg/kg) and/or resveratrol (25 mg/kg). All treatments caused changes in body weight, food intake, and liver/bw ratio. Acute treatment with novel complexes decreased the levels of TB and TP while elevated the activity of ALT, AST, GGT, ALP which subsequently indicated on the liver damage. All three complexes significantly reduced the levels of LPO, O2.−, NO2− and activity of CAT, while increasing the activity of SOD, GSH-Px, GR, GST, and level of GSH, implying that these compounds could provoke redox balance disruption in liver cells. Moreover, according to the histopathological observations, the novel Pt(IV) complexes exerted stronger hepatotoxicity than cisplatin. Possible protective effects of resveratrol were not detected and even combined with examined compounds it abolished the activity of the antioxidative system of the liver cells causing more intense toxicity. Further investigation is required to elucidate the effects of Pt-based drugs and resveratrol in the estradiol-rich environment of female rats as well their influence on male rats’ tissues.

In this study, a series of synthesized 3-(4-substituted benzyl)-5-isopropyl-5-phenylhydantoin derivatives as a potential antiproliferative and antimigratory agents were investigated. The possible antitumor mechanisms of investigated hydantoin derivatives were examined on human breast cancer cell line MDA-MB-231. The cells were treated with different concentrations of compounds (from 0.01 µM to 100 µM) during 24 h and 72 h. The proliferation index, nitric oxide production, apoptosis rate, and migration capacity were measured. The cell invasion potential was examined by measuring the level of MMP-9 and COX-2 gene expression. All tested compounds expressed antiproliferative activity and induced dose- and time-dependent increase in the level of nitrites. The investigated molecules significantly decreased cell survival rate, migration capacity and the expression levels of genes included in the process of tumor invasion. Obtained data suggest that the tested hydantoin derivatives express considerable antitumor activity by reducing cell division rate, elevating apoptosis level, and inhibiting the motility and invasiveness of breast cancer cells. The results obtained in this study indicate that investigated compounds express potential as a novel chemotherapeutic agents against breast cancer growth and progression. Keywords: Hydantoin derivatives, Breast cancer cell line MDA-MB-231, Proliferation, Apoptosis, Cell motility, Nitric oxide

Platinum(IV) complexes offer the potential to overcome cisplatin resistance of cancer cells, with possible improved selectivity. Resveratrol, a natural polyphenol with anticancer and antioxidant capacity, could limit the possible side effects of chemotherapeutics on healthy cells. This study investigates the effects of platinum(IV) complexes containing some esters of the ethylenediamine-N,N'-di-S,S-(2,2'-dibenzyl)acetate acid (H2 -S,S-eddba), and resveratrol on proliferation, migration, and redox balance of breast cancer (MDA-MB-231), choriocarcinoma (JEG-3), and human lung fibroblast (MRC-5) cell line. According to IC50 values, all complexes exhibited a significantly stronger antiproliferative effect on tested cell lines compared to cisplatin. Due to reduced adverse effects on MRC-5 cells, the complex containing ethyl-substituent (10 μM) was selected for further examination with resveratrol (25 μM) cotreatment. Resveratrol enhanced the survival of MRC-5 cells while diminished the viability of both used cancer cell lines when applied combined with selected complex. Furthermore, cotreatment of these two compounds decreased the migratory potential of tested cancer cell lines. The examined platinum(IV) complex was able to induce oxidative stress in all tested cell lines. Resveratrol proved to be efficient in protecting MRC-5 cells from complex-induced oxidative damage, while it significantly amplified antiproliferative, antimigratory, and prooxidative effects of platinum(IV) complex on both examined cancer cell lines. These findings may be valuable in elucidating the mechanism of action of platinum(IV) drugs, which should be further investigated.

Platinum(IV) complexes offer the potential to overcome cisplatin resistance of cancer cells, with possible improved selectivity. Resveratrol, a natural polyphenol with anticancer and antioxidant capacity, could limit the possible side effects of chemotherapeutics on healthy cells. This study investigates the effects of platinum(IV) complexes containing some esters of the ethylenediamine-N,N'-di-S,S-(2,2'-dibenzyl)acetate acid (H

Acetaminophen is widely used as an over-the-counter analgesic and antipyretic drug. The aim of the present study was to investigate the pro-oxidative effects of acetaminophen (300 mg/kg/day i.p.) and antioxidative effects of β-glucan (4 mg/kg/day i.p.) and/or vitamin C (100 mg/kg/day i.p.) on the blood parameters of treated rats. After 3 days of treatment, hematological and parameters of redox status were measured. Exposure of rats to acetaminophen caused significant changes in some hematological parameters and the glutathione redox cycle, leading to an increased concentration of oxidative stress parameters and the formation of lipid peroxidation, while the activities of antioxidant enzymes were decreased. Administration of β-glucan and/or vitamin C reduced lipid peroxidation and restored the levels of examined hematological and oxidative stress parameters and improved the activities of antioxidant enzymes. Obtained results demonstrated that acetaminophen has significant pro-oxidative effects and may disrupt redox balance in blood of rats, while the combination of β-glucan and/or vitamin C amplified the antioxidant defense potential and exhibited a strong hematoprotective activity against acetaminophen-induced toxicity. Therefore, β-glucan and vitamin C co-treatment may be a promising therapeutic option for the treatment of acute acetaminophen hematotoxicity.

The use of cisplatin in chemotherapy may provoke a deteriorating impact in many vital organs, suggesting the need for more selective derivatives and effective protective cotreatments. This study assesses the effects of three novel Pt(IV) complexes containing ethyl-, propyl- and butyl-esters of the ethylenediamine-N, N'-di-S, S- (2,2'-dibenzyl) acetic acid on liver injury markers, redox parameters, and cell morphology of female rat liver tissue in comparison to cisplatin. In addition, the study evaluates the possible protective effects of resveratrol as well. The rats were divided into ten groups and were administered intraperitoneally with a single dose of cisplatin (7.5 mg/kg) or Pt(IV) complexes (10 mg/kg) and/or resveratrol (25 mg/kg). All treatments caused changes in body weight, food intake, and liver/bw ratio. Acute treatment with novel complexes decreased the levels of TB and TP while elevated the activity of ALT, AST, GGT, ALP which subsequently indicated on the liver damage. All three complexes significantly reduced the levels of LPO, O

Fenitrothion is widely used organophosphate pesticide in agriculture and health programs, but besides, it causes several toxic effects. The present study was designed to evaluate the possible protective effects of selenium (0.5 mg/kg b.w.) and vitamin C (100 mg/kg b.w) on altered haematological, biochemical and oxidative stress parameters in the blood of rats orally treated with fenitrothion (20 mg/kg b.w) for 30 days. Fenitrothion caused changes in body weight, food and water intake, and some haematological and biochemical parameters. Fenitrothion altered the glutathione redox status (GSH and GSSG) and decreased activity of antioxidant enzymes (GSH-Px, GST, SOD and CAT), leading to a lipid peroxidation. Selenium and vitamin C, by improving the activity of antioxidants, reduced oxidative stress and a lipid peroxidation, maintaining the values of examined parameters to optimal levels. Therefore, selenium and vitamin C could be useful in providing protection of exposed non-target organisms including people from fenitrothion.

Cadmium (Cd) is a major environmental pollutant, which exerts adverse effects mainly by inducing oxidative stress. Coenzyme Q10(CoQ10) and vitamin E (VE), naturally occurring antioxidants, improve health condition by inactivating free radicals and enhancing antioxidative defence. The aim of our study was to investigate the protective role of CoQ10and/or VE pretreatment against Cd-induced haematotoxicity. Wistar albino rats were intramuscularly injected with CoQ10(20 mg/kg b.w.) and/or VE (20 IU/kg b.w.) or with saline (control group). After 24 h, Cd was injected intraperitoneally (0.4 mg/kg b.w.) and 1 day after, animals were sacrificed. Acute Cd intoxication caused significant changes in haematological and biochemical parameters and altered the glutathione cycle, leading to the formation of lipid peroxidation, while the concentrations and activities of antioxidants (vitamins C and E, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) were decreased. CoQ10and/or VE significantly maintained these values to near-normal levels, afforded additional protection by reducing lipid peroxidation and improved the levels of antioxidants in the blood. Plasma CoQ10and VE levels negatively correlated with oxidative damage parameters while positively correlated with antioxidative defence parameters. Regarding their effects, CoQ10and VE were in synergistic interaction. The present study suggested that CoQ10and VE combination may be beneficial in protecting from Cd-induced haematotoxicity and may be used as a preventive against acute Cd intoxication of exposed people.

Background: Hydantoin and its newly synthesized derivatives have recently become a focus of interest due to their numerous biological activities and newly emerging beneficial effects in different pathological conditions, including cancer. Objective: The aim of this study was to evaluate the possible anti-tumor mechanisms of a series of newly synthesized 3-(4-substituted benzyl)-5-isopropyl-5-phenylhydantoin derivatives in different aspects of cell physiology of human colon cancer cell line, HCT-116. Methods: The increasing concentrations of derivatives (0.01µM up to 100µM) were applied to cells during 24h, 48h, and 72h after which the evaluation of proliferation, apoptosis, oxidative/anti-oxidative status, nitrite production, and migration/invasion potential of treated cells was performed. Results: All tested compounds expressed the dose- and time-dependent anti-proliferative and pro-apoptotic activities against HCT-116 cells. The investigated derivatives induced a decrease in levels of oxidative stress parameters and an increase in levels of nitrite production by treated cells suggesting their significant antioxidative effects. The cell migration index and expression level of tumor invasion-promoting metalloproteinase- 9 (MMP-9) gene were significantly decreased after treatment with the tested hydantoin derivatives implicating their inhibitory role in colon cancer cell motility and invasion processes. The mRNA level of cyclooxygenase-2 (COX-2) gene as a pro-inflammatory gene related to colorectal carcinogenesis was reduced compared to values in the non-treated control cells indicating the significant anti-inflammatory/anti-tumor effects of these compounds. Conclusion: The obtained results show the significant anti-tumor potential of tested derivatives, especially 3- benzyl-5-isopropyl-5-phenylhydantoin and 3-(4-chlorobenzyl)-5-isopropyl-5-phenylhydantoin, suggesting their potential usage in the development of more effective chemotherapies.

Excessive use of organophosphate insecticides, including fenitrothion (FNT) can cause detrimental consequences in non-target organisms. Selenium (Se) and vitamin C (Vit C) possess protective abilities against various toxic compounds due to their antioxidative properties. Accordingly, the aim of the present study was to examine the possible ameliorative effects of Se and Vit C in hepatotoxicity induced by FNT. For the purpose of this study, male Wistar albino rats were divided into control and groups treated with Se (0.5 mg/kg b.w, as Na2SeO3) and Vit C (100 mg/kg b.w), FNT (20 mg/kg b.w) and FNT in cotreatment with Se and Vit C for 30 days. The current data showed a reduction in absolute and relative liver weight after FNT administration. Increased activities of liver enzymes (AST, ALT, ALP, LDH and GGT) indicated liver damage. FNT alone caused significant alterations in biochemical parameters (glucose and total bilirubin). Elevation in LPO level along with decreased activities of antioxidant enzymes (SOD, CAT, GSH-Px) and GSH content reflected the presence of oxidative stress. Coadministration of FNT with Se and Vit C exhibited hepatoprotective role confirmed by reduction of oxidative stress levels and restoration in the values of examined parameters. Because of their beneficial effects, Se and Vit C may be used in reducing injuries caused by pesticides.

Aspartame (ASP) is one of the most widely used nonnutritive sweeteners. This study investigates the chronic effects of ASP on hematological and biochemical parameters, and its effects on the oxidative/antioxidative status in the red blood cells of Wistar albino rats. Rats were provided with ASP (40 mg/kg/daily for six weeks) in drinking water. Increased food and fluid intake was observed in the ASP-treated rats. Total body mass was significantly decreased in the ASP-treated rats. Treatment with ASP caused an increase in the concentrations of glucose, cholesterol, LDL-cholesterol, and in the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as a decrease in the levels of HDL-cholesterol in the serum. A significant decline in the number of white blood cells (WBC) was observed after ASP uptake. Based on the results we conclude that ASP induces oxidative stress, observed as an alteration of the glutathione redox status, which leads to increased concentrations of nitric oxide (NO) and lipid peroxides (LPO) in the red blood cells. Changes in biochemical parameters, lipid metabolism, as well as changes in the levels of oxidative stress markers and the appearance of signs of liver damage indicate that chronic use of ASP can lead to the development of hyperglycemia, hypercholesterolemia and associated diseases. Ministry of Education, Science and Technological Development of Republic of Serbia {[}173041]

Since aspartame (L-aspartyl-L-phenylalanine methyl ester, ASP) is one of the most widely used artificial sweeteners, the aim of the present study was to investigate its effects on serum glucose and lipid levels as well as its effects on oxidative/antioxidative status in erythrocytes of rats. The experiment included two groups of animals: the control group was administered with water only, while the experimental group was orally administered with ASP (40 mg/kg b.w.) daily, for a period of six weeks. When compared with the control group, the group administrated with ASP indicated higher values of serum glucose, cholesterol and triglycerides. Significantly increased concentrations of superoxide anion (O-2(center dot-)), hydrogen peroxide (H2O2), peroxynitrite (ONOO-) and lipid peroxides (LPO) were recorded in the erythrocytes of ASP treated group in comparison to the control group. In the course of chronic ASP administration, the following was observed: the concentration of reduced glutathione (GSH) and the activity of catalase (CAT) increased. Thus, these findings suggest that long-term consumption of ASP leads to hyperglycemia and hyperlipidemia, as well as to oxidative stress in erythrocytes. Ministry of Education, Science and Technological Development of Republic of Serbia {[}173041]

We examined the influence of an Aphanizomenon flos-aquae bloom on the activities of antioxidant enzymes in the livers and gills of three cyprinids, Rutilus rutilus (roach), Blicca bjoerkna (white bream) and Carassius gibelio (Prussian carp) from the Gruza Reservoir (Serbia). We also studied tissue- and species-specific differences in the antioxidant response to the cyanobacterial bloom. The activities of total, copper zinc and manganese containing superoxide dismutases (Tot SOD, CuZn SOD, Mn SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and the biotransformation phase II enzyme glutathione-S-transferase (GST) were determined before and during the cyanobacterial bloom. B. bjoerkna exhibited higher antioxidant response to the cyanobacterial bloom than R. rutilus and C gibelio; liver Tot SOD, CuZn SOD and GST activities increased during the bloom only in this species. Liver Mn SOD activity in all three cyprinids increased during the bloom. A decrease in liver CAT and GSH-Px activities that was detected in all three species may be directly responsible for an enhanced susceptibility of fish to potential oxidative stress caused by the bloom. Tot SOD, CuZn SOD, Mn SOD, GSH-Px, GR and GST activities in gills were also inhibited during the bloom showing that the gills were affected more than the liver. The observed changes in the activities of aforementioned antioxidant enzymes during the cyanobacterial bloom suggest that these parameters could be important biomarkers for ecotoxicological risk in fish that inhabit ecosystems where A. flos-aquae blooms occur. (C) 2013 Elsevier Ltd. All rights reserved. Ministry of Education, Science and Technological Development of the Republic of Serbia {[}173041]

Nicotine is a potential inducer of oxidative stress, through which it can damage numerous biological molecules. The aim of our study was to investigate the prooxidative effects of nicotine and protective (additive or synergistic) effects of quercetin and vitamin C in the blood of experimental animals, to determine whether the combination of these antioxidants might be beneficial for clinical purposes. Wistar albino rats were receiving intraperitoneal nicotine injection (0.75 mg kg-1 per day) or saline (control group) or nicotine plus quercetin (40 mg kg-1 per day) and vitamin C (100 mg kg-1 per day) for three consecutive days. On day 4, we determined their blood lipid profile, liver enzymes, oxidative stress parameters, and antioxidative system parameters. Compared to untreated control, nicotine significantly increased total cholesterol, LDLcholesterol, triglycerides, liver enzymes (alanine transaminase, aspartate transaminase, and lactate dehydrogenase) and oxidative stress parameters (superoxide anion, hydrogen peroxide, and lipid peroxide) and decreased HDL-cholesterol, glutathione, and superoxide dismutase/catalase activity. Quercetin + vitamin C reversed these values significantly compared to the nicotine alone group. Our results confirm that nicotine has significant prooxidative effects that may disrupt the redox balance and show that the quercetin + vitamin C combination supports antioxidant defence mechanisms with strong haematoprotective activity against nicotine-induced toxicity. In practical terms, this means that a diet rich in vitamin C and quercetin could prevent nicotine-induced toxicity and could also be useful in the supportive care of people exposed to nicotine.

We investigated the biochemical and ultrastructural changes in the liver of the freshwater fish, European perch (Perca fluviatilis), in response to Aphanizomenon flos-aquae bloom in the Gruza Reservoir, Serbia. The activities of total manganese- and copper zinc-containing superoxide dismutase (Tot SOD, Mn-SOD, Cu/Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and biotransformation phase II enzyme glutathione-S-transferase (GST), as well as concentrations of total glutathione (GSH) and sulfhydryl (-SH) groups were examined before and during the bloom period. Mn-SOD activity was significantly higher, while the activities of Cu/Zn-SOD, CAT and GSH-Px and the concentration of the -SH groups were significantly lower during the bloom. The ultrastructure of the liver revealed necrotic and apoptotic damage to the hepatocytes during the bloom period. Our work represents the first study to report the influences of an Aphanizomenon flos-aquae bloom in the Gruza Reservoir on antioxidant biomarkers and on histopathological alterations in the liver of the freshwater fish European perch (Perca fluviatilis).

The aim of this study was to investigate the protective role of coenzyme Q(10) (CoQ(10), 20mg/kg) and Vitamin E (Vit E, 20 IU/kg) alone or in combination against cadmium (Cd, 0.4 mg/kg) induced lipid peroxidation and changes in antioxidant defense system in the rat testes. The obtained results showed that Cd increased lipid peroxidation in the testes, suggesting that Cd-induced oxidative stress, while CoQ(10) and Vit E treatment reversed this change to control values. Acute intoxication with Cd was followed by significantly decreased activity of antioxidant enzymes (SOD, CAT, GSH-Px, GR and GST). Vitamins C and E concentrations also significantly declined in Cd-exposed rat testes. Treatment with CoQ(10) and Vit E reversed Cd-induced alterations of antioxidant defense system and significantly prevented Cd-induced testes damage. These results suggest that both CoQ(10) and Vit E function as a potent antioxidant in protection of rats testes against the oxidative stress induced by Cd.

In the present study, we evaluated changes of both oxidative stress marker concentrations in erythrocytes and values of blood pressure, as well as their relation during short-term estradiol therapy in preeclampsia. Serum estradiol concentrations were also recorded. The results of this study showed significant decrease of mean arterial pressure (MAP) values during estradiol therapy, whereas there was no significant change in serum estradiol concentrations. Decreased concentrations of superoxide anion (O(2)(-)), hydrogen peroxide (H(2)O(2)), nitrite (NO(2)(-)), peroxynitrite (ONOO(-)) and lipid peroxide (LPO) were found during estradiol therapy in erythrocytes. No changes were found in the activity of gluthatione-S-transferase (GST). The decrease of MAP values was positively correlated with the reduction of concentrations of O(2)(-), H(2)O(2), NO(2)(-) and ONOO(-) in erythrocytes during estradiol therapy. The obtained results suggest that short-term intramuscular administration of estradiol shows antioxidative effects in erythrocytes and reduces blood pressure in preeclampsia.

The effects of selenium (Se) on antioxidant defense system in liver and kidneys of rats with cadmium (Cd)-induced toxicity were examined. Cd exposure (15 mg Cd/kg b.m./day as CdCl2 for 4 weeks) resulted in increased lipid peroxidation (LP) in both organs (p

Nicotine is a potential inducer of oxidative stress, through which it can damage numerous biological molecules. The aim of our study was to investigate the prooxidative effects of nicotine and protective (additive or synergistic) effects of quercetin and vitamin C in the blood of experimental animals, to determine whether the combination of these antioxidants might be beneficial for clinical purposes. Wistar albino rats were receiving intraperitoneal nicotine injection (0.75 mg kg-1 per day) or saline (control group) or nicotine plus quercetin (40 mg kg-1 per day) and vitamin C (100 mg kg-1 per day) for three consecutive days. On day 4, we determined their blood lipid profile, liver enzymes, oxidative stress parameters, and antioxidative system parameters. Compared to untreated control, nicotine significantly increased total cholesterol, LDL-cholesterol, triglycerides, liver enzymes (alanine transaminase, aspartate transaminase, and lactate dehydrogenase) and oxidative stress parameters (superoxide anion, hydrogen peroxide, and lipid peroxide) and decreased HDL-cholesterol, glutathione, and superoxide dismutase/catalase activity. Quercetin + vitamin C reversed these values significantly compared to the nicotine alone group. Our results confirm that nicotine has significant prooxidative effects that may disrupt the redox balance and show that the quercetin + vitamin C combination supports antioxidant defence mechanisms with strong haematoprotective activity against nicotine-induced toxicity. In practical terms, this means that a diet rich in vitamin C and quercetin could prevent nicotine-induced toxicity and could also be useful in the supportive care of people exposed to nicotine., Nikotin je potencijalni induktor oksidacijskoga stresa, preko kojega može oštetiti brojne biološke molekule. Cilj našega istraživanja bio je ispitati prooksidacijsko djelovanje nikotina i zaštitno (aditivno ili sinergističko) djelovanje kvercetina i vitamina C u krvi eksperimentalnih životinja te utvrditi može li kombinacija tih antioksidansa biti korisna u kliničke svrhe. Wistar albino štakori primali su intraperitonealno injekciju nikotina (0,75 mg kg-1 po danu) ili fiziološke otopine (kontrolna skupina) ili nikotina s kvercetinom (40 mg kg-1 po danu) i vitaminom C (100 mg kg-1 po danu) tri uzastopna dana. Četvrtoga dana odredili smo lipidni profil u krvi, jetrene enzime, parametre oksidacijskoga stresa i antioksidacijskoga sustava. U usporedbi s netretiranom kontrolnom skupinom, nikotin je značajno povećao ukupni kolesterol, LDL-kolesterol, trigliceride, jetrene enzime (alanin transaminaze, aspartat transaminaze i laktat dehidrogenaze) i parametre oksidacijskoga stresa (superoksid anion, vodikov peroksid i lipidne perokside), a smanjio HDL-kolesterol, glutation i aktivnosti superoksid dismutaze/katalaze. Kvercetin i vitamin C značajno su utjecali na te vrijednosti u odnosu na skupinu samo s nikotinom. Naši rezultati potvrdili su značajno prooksidacijsko djelovanje nikotina koje može poremetiti redoks ravnotežu i pokazuje da kombinacija kvercetina i vitamina C podržava antioksidacijske obrambene mehanizme s jakim hematoprotekcijskim aktivnostima protiv nikotinom izazvane toksičnosti. Možemo zaključiti da prehrana bogata kvercetinom i vitaminom C može koristiti kao prevencija nikotinom inducirane toksičnosti te da kombinacija tih dvaju antioksidansa može biti korisna u kliničkom oporavku ljudi izloženih nikotinu.

Reduced migration capacity of trophoblast cells leads to poor placentation and correlates with severe pregnancy disorders such as intrauterine growth restriction and preeclampsia. Neuropeptide Y (NPY) is sympathetic cotransmitter involved in various physiological processes and its levels are significantly increased in preeclamptic pregnancy compared to healthy pregnancy. In this study the prooxidative role of NPY and its effects on migration capacity of human trophoblast cell line JEG-3 were investigated together with the effects of nitric oxide (NO) depletion, a molecule that was shown to play an important role in promoting cell migration. The cells were treated for 24 h (short-term stimulation) and 72 h (long-term stimulation) respectively with 1 nM NPY. Oxidative/antioxidative status and the migration index of cells were measured. The results showed increased concentrations of oxidative stress parameters (O2 •–, H2O2) and molecules of the antioxidant defense system (reduced glutathione and oxidized glutathione), while the levels of intracellular nitrites (indicators of NO) and cell migration index were significantly decreased in trophoblast cells treated with NPY (both at 24 h and 72 h of exposure) compared to the control cells. These results suggest that NPY may significantly contribute to reduced migration capacity of trophoblast cells by generating oxidative stress and reducing the bioavailability of NO. The final publication is available at [http://journals.tubitak.gov.tr/biology/issues/biy-17-41-2/biy-41-2-5-1606-73.pdf] Turkish Journal of Biology (2016)

After enzymic biotransformation, molsidomine (MO) acts via the metabolite 3-morpholmosydnonimine (SIN-1) through spontaneous liberation of nitric oxide (NO) and superoxide (O-2(.-)). The aim of this study was to compare the effects of MO and its active metabolite SIN-1 on the redox status of rat erythrocytes and reticulocytes. Rat erythrocyte as well as reticulocyte-rich red blood cell (RBC) suspensions were aerobically incubated (2h, 37 degrees C) without (control) or in the presence of different concentrations of MO or SIN-1. In rat erythrocytes, biotransformation of MO resulted in the production of NO and nitroxyl (NO-). Endogenous superoxide anion (O-2(.-)) participated in peroxynitrite generation. SIN-1 simultaneously liberated NO and O-2(.-), which formed peroxynitrite (at least in part), but the liberated NO predominantly reacted with haemoglobin, forming methaemoglobin in erythrocytes. In reticulocytes, MO and SIN-1 caused an increase in the levels of both nitrite and 3-nitrotyrosine (an indicator of peroxynitrite), whereas they decreased the level of O-2(.-). In reticulocytes, MO was metabolized into SIN-1 which led to the generation of NO, which reacted with O-2(.-) (endogenous or exogenous) forming reactive nitrogen species. In conclusion, there are two metabolic pathways for MO biotransformation: one causing NO and NO- generation predominantly in erythrocytes and the other, via SINA metabolism, in reticulocytes. The main difference between the action of MO and SIN-1 was that the latter caused oxidative damage in RBCs. Copyright (c) 2006 John Wiley & Sons, Ltd. null

This study examines the responses of antioxidant parameters in the white muscle of four freshwater fish species: Rutilus rutilus (roach), Blicca bjoerkna (white bream), Carassius gibelio (Prussian carp) and Perca fluviatilis (European perch) after exposure to a bloom of Aphanizomenon flos-aquae (Cyanobacteria) in the Gruza Reservoir in Serbia. The set of analyzed biomarkers included the activities of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and biotransformation phase II enzyme glutathione-S-transferase (GST), and the concentrations of total glutathione (GSH) and sulfhydryl (-SH) groups that were measured before and during the bloom. Our results show that SOD activity in C. gibelio and P. fluviatilis, GSH-Px and GST activities in all four fish, GR activity in R. rutilus and C. gibelio and the -SH group concentration in P. fluviatilis markedly decreased during the bloom. The activity of CAT in all four fish and the concentration of GSH in B. bjoerkna and P. fluviatilis significantly increased. The observed changes in nonspecific antioxidant biomarkers in fish muscle (especially CAT, GSH-Px and GST activities) suggest that these parameters could be useful tools in environmental monitoring programs of the freshwater ecosystems where cyanobacterial blooms occur. Ministry of Education, Science and Technological Development of the Republic of Serbia {[}173041]

The aim of this study was to investigate the protective effects of oestradiol (E2, 4 mg kg(-1) b.w.i.p.) against cadmium-induced (Cd, 2 mg kg(-1) b.w. i.p.) blood changes in rats. Cadmium induced a significant decline in haemoglobin, haematocrit, and total erythrocyte, lymphocyte, and thrombocyte count, whereas total leukocytes and granulocytes increased. A significant increase was also observed in serum cholesterol, triglycerides, glucose, AST, and ALT activities, whereas total protein and albumin levels dropped significantly. Administration of E2 in combination with Cd alleviated most of these adverse effects. In terms of oxidative stress, Cd significantly increased oxygen-free radicals (O-2-and H2O2) in neutrophils and lipid peroxidation in erythrocytes, whereas E2 treatment reversed these changes to control values. Acute Cd poisoning significantly lowered antioxidant enzyme (SOD and CAT) activity and the level of non-enzymatic antioxidants (GSH and vitamin E), while increasing in GSSG. Treatments with E2 reversed Cd-induced effects on the antioxidant defences and significantly lowered Cd-induced oxidative damage in erythrocytes. This study suggests that exogenous E2 effectively restores redox balance in rat erythrocytes and counters adverse haematological and biochemical effects of Cd poisoning. It also improves the antioxidant capacity of erythrocytes, acting in synergy with endogenous antioxidants. Ministry of Education, Science and Technological Development of Republic of Serbia {[}173041]

To examine effects of exogenous Cd on the kidney antioxidant defense system (AOS) and the possible protective role of Se against Cd toxicity, male Wistar albino rats (2 months old) were exposed during 30 days to oral intake of 200 ppm Cd (as CdCl2), 0.l ppm Se (as Na-selenite) or to the same doses of Cd / Se, simultaneously. Marked accumulation of Cd (23.44 +/- 0.69 micrograms/g w.m.) and marked alterations of AOS, resulting in kidney injury (renal pseudohypertrophy), were found in Cd-treated rats. Activities of total superoxide dismutase (SOC, EC 1.15.1.1), manganese-containing superoxide dismutase (MnSOD) and selenium-dependent glutathione peroxidase (Se GSH-Px, EG 1.11.1.9) were significantly reduced, whereas that of glutathione-S-transferase (CST, EC 2.5.1.18) and vitamin E (vit E) concentration were significantly increased in the kidneys of Cd-treated rats. Kidney catalase (CAT, EC 1.11.1.6) activity, ascorbic acid (AsA) and red blood cell glutathione (GSH, GSSG) levels were not markedly influenced by CD uptake. In kidneys of Se treated rats, the activities of total SOD, copper-zinc-containing superoxide dismutase (CuZnSOD) and GST were significantly increased Activities of kidney CAT and Se GSH-Px were largely unchanged, whereas significant increases of the kidney AsA and vit E concentrations occurred. In Cd + Se-cotreated rats, the kidney activities of MnSOD, CAT and Se GSH-Px, as well as vit E concentration, were the same as in controls, whereas CuZnSOD and GST activities and concentration of AsA exceeded normal values. These data indicate that Se only partially improves the AOS that is insufficient to prevent Cd-induced nephrotoxicity.

Cisplatin (Cis-diamminedichloroplatinum II, CP) is an important chemotherapeutic agent, useful in the treatment of several cancers, but with several side effects such as nephrotoxicity. The present study investigated the possible protective effect of selenium (Se) against CP-induced oxidative stress in the rat kidneys. Male Wistar albino rats were injected with a single dose of cisplatin (7 mg CP/kg b.m., i.p.) and selenium (6 mg Se/kg b.m, as Na2SeO3, i.p.), alone or in combination. The obtained results showed that CP increased lipid peroxidation (LPO) and decreased reduced glutathione (GSH) concentrations, suggesting the CP-induced oxidative stress, while Se treatment reversed this change to control values. Acute intoxication of rats with CP was followed by statistically significant decreased activity of antioxidant defense enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST). Treatment with Se reversed CP-induced alterations of antioxidant defense enzyme activities and significantly prevented the CP-induced kidney damage. Ministry of Science of Republic of Serbia [173041]

Stimulated erythropoiesis and reticulocytosis can be induced by daily bleeding, or by phenylhydrazine (PHZ) treatment. We compared the in vivo effects of PHZ and bleeding treatment on haematological, energy and redox status parameters in red blood cells (RBC) of rats. The results showed that all followed haematological parameters were significantly lower in bleeding, compared to PHZ-treated rats. PHZ induced even 2.58-fold higher reticulocytosis as compared to bleeding treatment. Although PHZ induced higher reticulocytosis, respiration intensity and energy production was lower than in bleeding-induced reticulocytes. These alterations were the consequence of increased superoxide anion and peroxynitrite concentrations in PHZ-treated rats. Bleeding treatment resulted in increased activity of an antioxidative enzyme, superoxide dismutase. In conclusion, differences in these two experimental models for reticulocytosis may be used as tools for appropriate pharmacological testing of redox-active substances considering energy and redox processes, as well as apoptosis pathways.

Although cisplatin (cisPt) is one of the most often used cytotoxic drugs in the treatment of cancer, its clinical application is associated with nephrotoxicity and a cumulative anemia. In this study, we evaluated posible protective effects of selenium (Se) on hematological and oxidative stress parameters in rats, acutely treated with cisPt. Four groups of Wistar albino rats included control rats, cisPt-treated (7.5 mg/kg of body weight of cisPt, i.p.), Se-treated (6 mg/kg of body weight of Na(2)SeO(4), i.p.), and Se and cisPt co-treated rats. The rats were killed 72 h after treatment; hematological and oxidative stress parameters were followed in red blood cells. The results showed depletion in platelet number induced by high acute doses of cisPt and strong utilization of reduced glutathione, resulting in elevation of GSSG/2 GSH ratio. Se treatment was followed by stimulated erythropoiesis, increased lipid peroxidation, and GSH depletion. Se and cisPt co-treatment were followed by stimulated erythropoiesis and significant recovery of reduced glutathione status when compared with cisPt-treated rats. In conclusion, acute doses of Se and cisPt primarily act as pro-oxidants. CisPt influenced antioxidative properties of exogenous Se and their synergistic effects may partially participate in protection against cisPt-induced toxicity.

The present study was designed to investigate whether oxidative stress occurred to erythrocytes in preeclampsia and was related to disease. Indicative markers of oxidative stress and changes in antioxidant defense system were assayed in the erythrocytes of 22 healthy pregnant and 20 women with preeclampsia. Results of our work indicated high concentration of hydrogen peroxide, nitrite, peroxynitrite and lipid peroxides in preeclampsia compared to healthy pregnant women. Concentration of superoxide anion was lower in preeclamptic women. There were no differences in concentrations of vitamin E, reduced glutathione and oxidized glutathione. Activity of glutathione-S-transferase (GST) was higher while activities of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) were lower in preeclamptic women. There were no differences in glutathione peroxidase (GSH-Px) activity between the two investigated groups. These results suggest that preeclampsia was characterized by oxidative stress and alteration of antioxidative defense system by disbalance in oxidative/antioxidative status of erythrocytes.

Our study investigated the possible protective effects of coenzyme Q 10 (CoQ 10 ) and Vitamin E (Vit E) alone or in combination against cadmium (Cd) induced alterations of antioxidant defense system in the rat heart. Male Wistar rats were injected with a single dose of CdCl 2 (0.4 mg Cd/kg BW i.p.), CoQ 10 (20 mg CoQ 10 /kg BW i.m.) and Vit E (20 IU Vit E/kg BW i.m.), alone or in combination. Acute intoxication of rats with Cd were followed by significantly increased activity of antioxidant defense enzymes (CuZn SOD, GSH-Px, GST and GR), while the activity of Mn SOD was decreased in the heart. The treatment with Cd significantly decreased Vit C and Vit E concentrations. Treatment with CoQ 10 and Vit E reversed Cd-induced alterations of antioxidant defense system. The obtained results support the assumption that CoQ 10 and Vit E functions cooperatively with endogenous antioxidants and diminished toxic effects of Cd in rat heart.

Molsidomine (MO) is an established drug in treatment of coronary heart disease. Considering that MO is a donor of nitric oxide (NO) and a superoxide anion radical (O2*-), which forms peroxynitrite, a very toxic radical, the aim of this study was further elucidation of molecular mechanisms of MO action, particularly effects on prooxidative-antioxidative status of rat erythrocytes.Rat (Wistar albino, male, 250-300 g of b.m.) erythrocyte suspensions were aerobically incubated (120 min, 37 degrees C) without (control) or with MO (0.1, 0.25, 0.5, 1.0 and 1.5 mM). Concentrations of reactive oxygen species, methemoglobin, Heinz bodies, lipid peroxides, vitamins and glutathione, as well as activities of enzymes of the antioxidative defense system (AOS) were evaluated using standard techniques.Molsidomine increases nitrite concentrations (indicating NO+ level), hydroxylamine (indicating NO- level), 3-nitro-tyrosine (indicating ONOO- level) and H2O2, but decreases O2*- level in a dose-dependent manner (changes are statistically significant only with high doses of molsidomine--1.0 and 1.5 mM). These alterations were followed by partial cells damage, increased formation of Heinz bodies, but there were no changes in MetHb and lipid peroxide levels. The defense response of erythrocytes to evident oxidative stress includes increased Vitamin E and Vitamin C concentrations (nonenzymatic components ofAOS), as well as decreased glutathione (reduced and oxidized) levels. Activities ofAOS enzymes remain unchanged.Experimental doses of MO induce oxidative stress in rat erythrocytes. However, the first line of AOS is successful in the cellular defence response.

Chronic exposure of adult rats to dietary intake of cadmium (15 mg CdCl2/day/kg for 30 days) leads to development of anemia and thrombocytosis. Anemia is characterized by significant reticulocytosis (13.1 +/- 1.0%), anysocytosis, poikilocytosis, iron deficiency and marked alterations of antioxidant and metabolic status of red blood cells. Activities of SOD, catalase, GPx and GR were significantly increased in red blood cells of cadmium-treated rats. In treated animals cadmium induced an increase of red cell reduced and oxidized glutathione with no changes of GSSG/GSH ratio. However, significant reduction of lipid peroxidation was found. Plasma levels of tocopherol and ascorbate, as well as activity of glutathione-S-transferase, were all significantly increased in cadmium-treated rats. The energy metabolism of red blood cells was deeply altered in cadmium-treated rats. The levels of ATP, ADP, AMP and TAN were significantly increased while ATP/ADP ratio and adenylate energy charge (AEC) were significantly reduced. The level of 2,3-BPG was somewhat lower, but 2,3-BPG/Hb ratio was considerably higher, in red blood cells of cadmium-treated rats.

The aim of our study was to investigate the possible protective role of coenzyme Q10 (CoQ10) administration on ascorbic acid (AsA), vitamin E (vit E), and lipid peroxide (LP) concentrations in the blood of rats chronically treated with cadmium. Results were compared to those obtained in control animals, as well as to those obtained in animals treated with olive oil. Compared to that of the control animals, the AsA concentration was significantly increased in rats treated with CoQ10 and olive oil, whereas vit E concentration was significantly increased in animals treated with cadmium, CoQ10, or cadmium + CoQ10. A significant decrease in LP concentration was noted in animals treated with cadmium or with cadmium + CoQ10o, whereas a significant increase was seen in animals treated with olive oil. Compared to that of the animals treated with olive oil, the ascorbic acid concentration was significantly decreased in rats treated with cadmium or with cadmium + CoQ10, whereas vit E concentration was significantly increased in animals treated with cadmium, CoQ10, or cadmium + CoQ10. LP concentration was significantly decreased in rats treated with cadmium, CoQ10, or cadmium + CoQ10. Our study showed that CoQ10 administration in rats chronically exposed to exogenous cadmium exerts beneficial effects on the nonenzymatic components of the antioxidant defense system, such as AsA and vit E, resulting in a decreased concentration of LP in the blood.