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ABSTRACT: 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 Na(2)SeO(3), 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.
International Journal of Molecular Sciences 01/2012; 13(2):1790-803. · 2.60 Impact Factor
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ABSTRACT: 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.
Biological trace element research 09/2011; 142(3):660-70. · 1.92 Impact Factor
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ABSTRACT: 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.
Acta Biologica Hungarica 06/2011; 62(2):122-32. · 0.59 Impact Factor
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ABSTRACT: 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.
Reproductive Toxicology 11/2009; 29(2):231-6. · 3.23 Impact Factor
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ABSTRACT: 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.
Reproductive Toxicology 11/2009; 29(2):191-7. · 3.23 Impact Factor
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ABSTRACT: This article is dedicated to the memory of Radoslav V. Žikić, Professor of General Physiology and Ecotoxicology at Faculty of Science, University of Kragujevac, who died in October 2008. The article consists of two parts. In the first part, a brief review of Žikić's scientific work is presented. The second part is the list of major scientific papers published during his life. In this way, we want to express our appreciation for his contribution to the development of the physiology of antioxidant defense system in Serbia, as well as his contribution to the development of Faculty of Science in Kragujevac.
UDC 929 Žikić V. R. 01/2009; 31:133-138591.
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ABSTRACT: 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.
Reproductive Toxicology 03/2008; 25(2):213-8. · 3.23 Impact Factor
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ABSTRACT: 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) (0.4mg Cd/kg BW i.p.), CoQ(10) (20mg CoQ(10)/kg BW i.m.) and Vit E (20IU 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.
Environmental Toxicology and Pharmacology 09/2006; 22(2):219-24. · 1.47 Impact Factor
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ABSTRACT: After enzymic biotransformation, molsidomine (MO) acts via the metabolite 3-morpholinosydnonimine (SIN-1) through spontaneous liberation of nitric oxide (NO) and superoxide (O). 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 (2 h, 37°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) participated in peroxynitrite generation. SIN-1 simultaneously liberated NO and O, 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. In reticulocytes, MO was metabolized into SIN-1 which led to the generation of NO, which reacted with O (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 SIN-1 metabolism, in reticulocytes. The main difference between the action of MO and SIN-1 was that the latter caused oxidative damage in RBCs. Copyright © 2006 John Wiley & Sons, Ltd.
Cell Biochemistry and Function 01/2006; 25(3):251 - 258. · 1.77 Impact Factor
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ABSTRACT: 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.
Medicinski pregled 02/2003; 56 Suppl 1:73-7.
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ABSTRACT: After enzymic biotransformation, molsidomine (MO) acts via the metabolite 3-morpholinosydnonimine (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 (2 h, 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 SIN-1 metabolism, in reticulocytes. The main difference between the action of MO and SIN-1 was that the latter caused oxidative damage in RBCs.
Cell Biochemistry and Function 25(3):251-8. · 1.77 Impact Factor
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ABSTRACT: 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.
Reproductive Toxicology.
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ABSTRACT: 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 (O2−), hydrogen peroxide (H2O2), nitrite (NO2−), 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 O2−, H2O2, NO2− 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.
Reproductive Toxicology.
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ABSTRACT: The aim of this study was to investigate the protective role of coenzyme Q10 (CoQ10, 20 mg/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 CoQ10 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 CoQ10 and Vit E reversed Cd-induced alterations of antioxidant defense system and significantly prevented Cd-induced testes damage. These results suggest that both CoQ10 and Vit E function as a potent antioxidant in protection of rats testes against the oxidative stress induced by Cd.
Reproductive Toxicology.
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ABSTRACT: Our study investigated the possible protective effects of coenzyme Q10 (CoQ10) 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 CdCl2 (0.4 mg Cd/kg BW i.p.), CoQ10 (20 mg CoQ10/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 CoQ10 and Vit E reversed Cd-induced alterations of antioxidant defense system. The obtained results support the assumption that CoQ10 and Vit E functions cooperatively with endogenous antioxidants and diminished toxic effects of Cd in rat heart.
Environmental Toxicology and Pharmacology.
