Snežana D. Marković

Cadmium-induced lipid peroxidation and changes in antioxidant defense system in the rat testes: protective role of coenzyme Q10 and Vitamin E.

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.

Antioxidant, Antimicrobial and Antiproliferative Activities of Five Lichen Species

The antioxidative, antimicrobial and antiproliferative potentials of the methanol extracts of the lichen species Parmelia sulcata, Flavoparmelia caperata, Evernia prunastri, Hypogymnia physodes and Cladonia foliacea were evaluated. The total phenolic content of the tested extracts varied from 78.12 to 141.59 mg of gallic acid equivalent (GA)/g of extract and the total flavonoid content from 20.14 to 44.43 mg of rutin equivalent (Ru)/g of extract. The antioxidant capacities of the lichen extracts were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals scavenging. Hypogymnia physodes with the highest phenolic content showed the strongest DPPH radical scavenging effect. Further, the antimicrobial potential of the lichen extracts was determined by a microdilution method on 29 microorganisms, including 15 strains of bacteria, 10 species of filamentous fungi and 4 yeast species. A high antimicrobial activity of all the tested extracts was observed with more potent inhibitory effects on the growth of Gram (+) bacteria. The highest antimicrobial activity among lichens was demonstrated by Hypogymnia physodes and Cladonia foliacea. Finally, the antiproliferative activity of the lichen extracts was explored on the colon cancer adenocarcinoma cell line HCT-116 by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) viability assay and acridine orange/ethidium bromide staining. The methanol extracts of Hypogymnia physodes and Cladonia foliacea showed a better cytotoxic activity than the other extracts. All lichen species showed the ability to induce apoptosis of HCT-116 cells.

Oxidative stress and changes in antioxidative defense system in erythrocytes of preeclampsia in women.

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.

Antiproliferative and proapoptotic activities of methanolic extracts from Ligustrum vulgare L. as an individual treatment and in combination with palladium complex.

The aim of this study is to examine the growth inhibitory effects of methanolic leaf and fruit extracts of L. vulgare on HCT-116 cells over different time periods and their synergistic effect with a Pd(apox) complex. The antiproliferative activity of plant extracts alone or in combination with the Pd(apox) complex was determined using MTT cell viability assay, where the IC50 value was used as a parameter of cytotoxicity. Results show that antiproliferative effects of L. vulgare extracts increase with extension of exposure time, with decreasing IC50 values, except for 72 h where the IC50 values for methanolic leaf extract were lower than for the fruit extract. The Pd(apox) complex alone had a weak antiproliferative effect, but combination with L. vulgare extracts caused stronger effects with lower IC50 values than with L. vulgare extracts alone. The type of cell death was explored by fluorescence microscopy using the acridin orange/ethidium bromide method. Treatments with plant extracts caused typical apoptotic morphological changes in HCT-116 cells and co-treatments with Pd(apox) complex caused higher levels of apoptotic cells than treatment with plant extracts alone. The results indicate that L. vulgare is a considerable source of natural bioactive substances with antiproliferative activity on HCT-116 cells and which have a substantial synergistic effect with the Pd(apox) complex.

Combined effects of coenzyme Q10 and Vitamin E in cadmium induced alterations of antioxidant defense system in the rat heart

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.

Chemical composition, cytotoxic and antioxidative activities of ethanolic extracts of propolis on HCT-116 cell line.

BACKGROUND Propolis is a complex resinous sticky substance that honeybees collect from buds and exudates of various plants. Owing to its versatile biological and pharmacological activities, propolis is widely used in medicines, cosmetics and foods. The aim of this study was to evaluate the cytotoxic and antioxidative effects of various ethanolic extracts of propolis (EEPs) on human colon cancer cell line HCT-116 and compare them with their composition determined by HPLC-DAD. RESULTS The most abundant flavonoids in all samples were chrysin, pinocembrin and galangin (12.697-40.811 µg mg⁻¹), while the main phenolic acids were caffeic acid, ferulic acid and isoferulic acid. Dose- and time-dependent inhibition of growth of HCT-116 cells was observed for all propolis samples, with IC₅₀ values ranging from 26.33 to 143.09 µg mL⁻¹. Differences in cytotoxic activity of propolis samples were associated with differences in their composition. All EEP samples reduced both superoxide anion radical and nitrite levels and also had strong DPPH-scavenging activity. CONCLUSION All tested propolis samples had pronounced cytotoxic and antioxidative activities.

Vanillic Mannich bases: synthesis and screening of biological activity. Mechanistic insight into the reaction with 4-chloroaniline

One-step multi-component Mannich reaction of vanillin, aromatic amines (aniline and 4-chloroaniline), and cyclohexanone was successfully catalyzed by three chloroacetate ethanolamine based ionic liquids: diethanolammonium chloroacetate, and newly synthesized ethanolammoniumchloroacetate and N,N-diethylethanolammoniumchloroacetate. These reactions were performed in ethanol at room temperature. Mechanistic aspects of the reaction with 4-chloroaniline were considered by using density functional theory. The yield of obtained Mannich bases (MB-Cl and newly synthesized MB-H) was very good, while diastereoselectivity was excellent. These compounds were evaluated for their in vitro antioxidative activity by DPPH free radical scavenging assay. It was shown that both bases exhibit high activity against DPPH. In vitro cytotoxic and antioxidative effects of MB-Cl and MB-H against human breast carcinoma MDA-MB-231 and human colon carcinoma HCT-116 cell lines were also determined. The investigated Mannich bases show moderate or very weak cytotoxic effect on HCT-116 cells, while no cytotoxic effect was observed in the case of MDA-MB-231 cells. On the other hand, the tested substances induced oxidative stress in the treated cancer cell lines.

In Vitro Cytotoxic Activity of Origanum vulgare L. on HCT-116 and MDA-MB-231 Cell Lines.

In the present investigation, we examined the cytotoxic effect of methanolic extract from Origanum vulgare on HCT-116 and MDA-MB-231 cell line in vitro. In order to determine the cytotoxic effects we used an MTT viability assay. The results showed that cell growth is significantly lower in extract treated cells compared to untreated control. The effect of inhibition of cell growth was higher in the treatment of HCT-116 cell line than in MDA-MB-231. Based on the results it is determined that O. vulgare is a significant source of biologically active substances that have cytotoxic and antiproliferative activity in vitro.

The antioxidative effect of estradiol therapy on erythrocytes in women with preeclampsia.

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.

Chelate N,O-palladium(II) complexes: synthesis, characterization and biological activity

Four trans chelate N,O-palladium(II) complexes were synthetized starting from salicylaldehyde anil Schiff bases, as ligands. Their structures were elucidated using experimental and theoretical tools. The structures of the theoretically possible cis isomers are examined using the DFT method. The biological activity, in vitro cytotoxic and prooxidative effects against human breast carcinoma MDA-MB-231, human colon carcinoma HCT-116, and human fibroblast healthy MRC-5 cell lines of investigated compounds were determined. Schiff bases show a moderate or weak cytotoxic effect. On the other hand, complexes Pd-1 and Pd-6 show a significant cytotoxic effect on all three cell lines, with IC50 values in the range of 0.6 to 17.1 μM on HCT-116 cells, 7.2 to 55.6 μM on MDA-MB-231 cells and 34.5 to 48.1 μM on MRC-5 cells. Also, Pd-1 and Pd-6 induce extreme oxidative stress in the all treated cell lines. At this stage of investigation, Pd-1 and Pd-6 showed no selectivity towards cancer cells, i.e. they were also cytotoxic to MRC-5 cells to a similar extent. Taking into account these facts, it could be further investigated how the most active substances impact on the type of cell death (apoptotic and/or necrotic pathways).