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Hyperlipidaemia is a recognised risk factor for cardiovascular disease. In this study, the antihyperlipidaemic properties of spirulina (Arthrospira platensis, strain S2 from Serbia) were tested in adult Wistar rats before and after induction of hypercholesterolaemia by a high-fat diet (HFD) to compare the preventive with the curative effect. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT) and aspartate transaminase (AST) levels were measured in the blood samples. The chemical composition (lipids, proteins and cholesterol) and the content of bile acids in the faeces of the animals were also analysed. Feeding rats with an atherogenic diet for 10 weeks led to the successful development of hyperlipidaemia, as serum TC and LDL-C levels as well as lipids, cholesterol and bile acids in the animals’ faeces were significantly increased. Pre- and post-treatment with spirulina led to a reduction in serum LDL, TC and ALT levels. Administration of spirulina resulted in both a significant increase in primary bile acids excretion and a decrease in bile acids metabolism, with pre-treatment being more effective than post-treatment in some cases. These results suggest that increased excretion of bile acids as well as an effect on the gut microbiota may be the mechanism responsible for the anti-hyperlipidaemic activity of the tested spirulina strain.

The European corn borer (Ostrinia nubilalis, Hbn.), enters diapause, a strategy characterized by arrest of development and reproduction, reduction of metabolic rate and the emergence of increased resistance to challenging seasonal conditions as low sub-zero winter temperatures. The aim of this study was to investigate the potential role of inorganic elements in the ecophysiology of O. nubilalis, analysing their content in the whole body, hemolymph and fat body, both metabolically active, non-diapausing and overwintering diapausing larvae by ICP-OES spectrometer following the US EPA method 200.7:2001. O nubilalis as many phytophagous lepidopteran species maintain a very low extracellular sodium concentration and has potassium as dominant cation in hemolymph of their larvae. Changes in hemolymph and the whole body sodium content occur already at the onset of diapause (when the mean environmental temperatures are still high above 0 ºC) and remain stable during the time course of diapause when larvae of this species cope with sub-zero temperatures, it seems that sodium content regulation is rather a part of diapausing program than the direct effect of exposure to low temperatures. Compared to non-diapausing O. nubilalis larvae, potassium levels are much higher in the whole body and fat body of diapausing larvae and substantially increase approaching the end of diapause. The concentration of Ca, Mg, P and S differed in the whole body, hemolymph and fat body between non-diapausing and diapausing larvae without a unique trend during diapause, except an increase in their contents at the end of diapause.

All processes involved in metal homeostasis must be coordinated to provide sufficient, but not toxic, concentrations of important bioelements, and to minimize detrimental effects of toxic metals. Our previous studies dealing with the exposure of O. nubilalis non-diapausing larvae to dietary Cd demonstrated that exposure to higher concentrations of Cd caused delay in the development of larvae, induced oxidative stress and also induced defense mechanisms against the toxic effects of Cd. The aim of the present study was to evaluate how acute and chronic exposure of O. nubilalis larvae to increased concentrations of dietary Cd affected the balance of important bioelements. The concentration of bioelements was analyzed in larvae (after short-term exposure) and pupae (after long-term exposure). The short-term exposure of final instar larvae (L5) to Cd did not affect significantly the concentration of any of the analyzed bioelements, while the long-term exposure of developing larvae to higher concentrations of Cd caused increase in the concentrations of Ca, Mg and Na in pupae. The bioaccumulation factor, calculated for bioelements after long-term exposure to Cd, was higher for the most bioelements in groups fed with diet containing higher concentrations of Cd, except K which displayed the opposite trend. Pearson correlation coefficient showed positive correlations between Cd and Ca, Mg, Na, Fe, Cu and Zn, while negative correlation was observed between Cd and K. The results indicate that impact on the balance of important bioelements might be one of the mechanisms of cadmium toxicity and certainly raise numerous questions for future research.

Evidentne klimatske promene dovode do izmena ne samo u smislu zapremine već i raspodele padavina, pa su posledično sve češće smene perioda ekstremnih vodnih deficita i suficita. Vodni deficit i suficit utiču na rast i razvoj biljaka tako što dovode do inhibicije fotosinteze, oksidativnih oštećenja ćelijskih komponenti te promena u respiraciji. Cilj ove disertacije je bio da se utvrde efekti vodnog suficita i deficita na fiziološke, oksidativne i antioksidativne parametre kod dva hibrida kukuruza (ZP 555 i ZP 606). Vodnom suficitu su podvrgnute biljke u trajanju od 6, 24, 72 i 144 sati, a vodnom deficitu u trajanju od 8 i 15 dana, sa odgovarajućim kontrolnim biljkama. Listovi kontrolnih i tretiranih biljaka su korišteni za određivanje sledećih parametara: fizioloških (relativnog sadržaja vode (RWC), koncentracije fotosintetičkih pigmenata, solubilnih proteina, slobodnog prolina), oksidativnih (koncentracije malondialdehida – MDA i H2O2) i antiokdiativnih (neenzimskih - koncentracija polifenola, i enzimskih komponenti - aktivnosti antioksidativnih enzima: superoksid dismutase (SOD, EC 1.15.1.1), katalaze (CAT, EC 1.11.1.6), askorbat peroksidaze (APX, EC 1.11.1.11) i peroksidaza Klase III (POX, EC 1.11.1.7)). Rezultati dobijeni izlaganjem biljaka vodnom suficitu i deficitu su pokazali različit odgovor hibrida na poplavu i sušu i značajne interhibridne razlike kada je u odgovor na poplavu ili sušu. Promene u procesu fotosinteze su detektovane kroz promene koncentracije fotosintetičkih pigmenata. Pri uslovima vodnog suficita izmeren je porast koncentracije hlorofila a i b, te karotenoida kod hibrida ZP 555. Sa druge strane, smanjena koncentracija hlorofila b i karotenoida izmerena je kod hibrida ZP 606 nakon 24 sata vodnog suficita. Hibrid su imali istovetan odgovor na vodni deficit, gde je detektovano smanjenje koncentracije hlorofila a i karotenoida te povećanje koncentracije hlorofila b. Kao posledica vodnog suficita detektovana je i povećana koncentracij, Plants are continuously challenged by the rising incidence of drought and flooding as a consequence of global warming. These stresses may cause severe depression in the plant’s growth by inhibiting photosynthesis, inducing oxidative cell damage, and cell respiration changes. The present work aimed to study the effect of flooding and drought stress on physiological, oxidative, and antioxidative parameters in leaves of two maize hybrids (ZP 555 and ZP 606). Maize plants`leaves at the stage of three fully developed leaves were harvested after 6, 24, 72, and 144 hours of applied flooding stress and after 8 and 15 days after applied drought stress. Leaves from experimental plants and control plants were used for the determination of physiological (relative water content (RWC), the content of photosynthetic pigments and soluble proteins, proline), oxidative stress parameters (the content of malondialdehyde (MDA) and H2O2), as well as antioxidants (the total polyphenols content (Phe), and activity of antioxidative enzymes [catalase (CAT, EC 1.11.1.6), superoxide dismutase (SOD, EC 1.15.1.1), ascorbate peroxidases (APX, EC 1.11.1.11), and Class III peroxidases (POX, EC 1.11.1.7)]). Results indicated that drought and flooding stress-induced time-dependent changes of measured parameters and those hybrids differ in stress response. Changes in photosynthesis can be seen thought modifications in photosynthetic pigments concentration. An increase in the concentration of chlorophylls and carotenoids have been noted during flooding in ZP 555 hybrids. On the other hand, flooding stress decreased the chlorophyll b and carotenoid concentrations in ZP 606 hybrids. A decrease in the concentration of chlorophyll a and carotenoids and an increase in chlorophyll b concentration were a response of both examined hybrids on drought stress. Also, intensive protein synthesis was noted in both hybrids during flooding. More intensive oxidative stress levels were correlated with an i

Uzimajući u obzir klimatske promjene koje podrazumijevaju smanjenje količine padavina i porast temperatura, suša je postala globalni problem za koji se smatra da će biti aktuelan još dugo vremena u budućnosti. Osim problema koje stvara u brojnim životnim sferama, suša je jedan od najozbiljnijih faktora koji negativno utiče na poljoprivredu, s obzirom da nedovoljno vodosnabdijevanje negativno utiče na rast i razvoj biljaka. U uslovima suše povećana produkcija reaktivnih vrsta kiseonika može da izazove pomjeranje ravnoteže u ćelijskim oksidoredukcionim reakcijama u smjeru oksidacije te da dovede do nastanka oksidativnog stresa. Posljedice oksidativnog stresa su strukturna i funkcionalna oštećenja ćelijskih komponenti koja dovode do poremećaja u metabolizmu i funkcionisanju ćelije.Veoma važnu ulogu u toleranciji biljaka na stres izazvan sušom ima antioksidativni sistem zaštite koji neizbježno uključuje enzime superoksid dismutazu, katalazu, peroksidaze Klase III i askorbat peroksidazu, ali takođe i niskomolekularne antioksidante poput askorbata, glutationa, fenola i karotenoida. Posljednjih godina se naglo povećao interes za korištenje ekološki opravdanih i neinvazivnih sredstava kojima se unaprijeđuje problem vodosnabdijevanja biljaka, a velika pažnja je posvećena primjeni prirodnih aluminosilikata, od kojih je najpoznatiji zeolit. Iako nisu mnogobrojni, postoje radovi koji upućuju da ovaj prirodni mineral može značajno da doprinese poboljšanju vodnog režima biljaka zbog osobine vezivanja te uravnoteženog otpuštanja vode. U ovoj doktorskoj disertaciji predmet istraživanja je uključio dvije biljne vrste različite po tipu fotosintetičkog metabolizma i adaptivnim strategijama na prilagođavanje na sušu, a to su paradajz (Solanum lycopersicum L.) i kukuruz (Zea mays L.). Fokus istraživanja bio je ispitivanje mogućnosti primjene zeolita u svrhu sprječavanja ili ublažavanja posljedica stresa izazvanog sušom kod biljaka paradajza i kukuruza, ali i ispitivanje mogućeg različit, Taking into account climate change, which implies a precipitation decreasing and temperatures rising, drought has become a global problem that is considered to be relevant for a long time to come. In addition to the problems it creates in many spheres of life, drought is one of the most serious factors that negatively affects agriculture, given that insufficient water supply disrupts the growth and development of plants. The production of reactive oxygen species in drought conditions can cause an inbalance of cellular redox homeostasis in the direction of oxidation and lead to the formation of oxidative stress. The consequences of oxidative stress are structural and functional damages of cellular compartments which leads to disturbance of metabolism and cell function. A very important role in plant tolerance to drought stress has the antioxidant protection systems that inevitably include theenzymes superoxide dismutase, catalase, Class III peroxidases and ascorbate peroxidase, but also low molecular weight antioxidants such as ascorbate, glutathione phenol and carotenoids. In recent years, there has been a sharp increase in interest in the use of environmentally sound and non- invasive means to improve the water supply of plants, and much attention has been paid to the use of natural aluminosilicates, the most famous of which is zeolite. Although not numerous, there are studies that suggest that this natural mineral can significantly contribute to the improvement of the water regime of plants due to the binding properties and balanced release of water. In this PhD thesis, the subject of research included two plant species different in type of photosynthetic metabolism and adaptive drought adaptation strategies, namely tomatoes (Solanum lycopersicum L.) and maize (Zea mays L.). The focus of research was to examine the possibility of using zeolite to prevent or mitigate the effects of drought stress in tomato and maize plants, but also to examine the possible diff

Tumori predstavljaju drugi vodeći uzrok smrti u svetu (posle kardiovaskularnih bolesti) i procena je da će učestalost pojave tumora u budućnosti porasti. Hemioterapija je jedna od najčešće korišćenih metoda lečenja tumora koju često prate sporedni sistemski štetni efekti. S obzirom da lečenje tumora jednim terapeutskim agensom često rezultuje ograničenim kliničkim ishodom, kombinovane terapije mogu sinergistički podići nivo antitumorske aktivnosti, dok sniženjem doze svakog pojedinačnog agensa se mogu umanjiti štetni efekti. Istovremena aplikacija različitih terapeutskih agenasa zahteva dostavnu platformu kako bi se omogućila normalizacija farmakokinetike i farmakodinamike agenasa. Fulerenol C60(OH)24 predstavljaju pogodnu platformu za dostavu lekova zbog svojih fizičko-hemijskih i bioloških karakteristika. U vodenom rastvoru fulerenol se nalazi u obliku negativno naelektrisanih polianjonskih nanočestica koje poseduju veliku površinu i imaju mogućnost vezivanja pozitivno naelektrisanih hemioterapeutika kao što je doksorubicin (DOX), kao i pozitivnih jona metala, u ovom slučaju Fe2+. Osnovna biološka karakteristika fulerenola je da ima ulogu antioksidativnog agensa. U ovom radu iskorišćene su fizičkohemijske osobine fulerenolskih nanočestica (FNP), DOX-a i Fe2+ u cilju formiranja stabilnih nanokompozita FNP/DOX i FNP/Fe2+. Nanokompoziti su okarakterisani različitim fizičkohemijskim metodama, pri čemu je ustanovljeno da su čestice nanokompozita FNP/DOX veličine između 20 i 58 nm, naelektrisanja od -6 mV, čestice nanokompozita FNP/Fe2+ veličine između 11 i 60 nm, naelektrisanja od -30.8 mV, i diskoidalne morfologije. Oba nanokompozita imaju dobru stabilnost u vodenom rastvoru, što ih čini biokompatibilnim i pogodnim za primenu u biomedicini. FNP dekorisan DOX-om, u obliku nanokompozita FNP/DOX, omogućava značajno obimniji unos DOXa u ćelije i smanjuje procenat ćelija u G2M fazi ćelijskog ciklusa, u odnosu na samostalnu primenu DOX-a, kod malignih ćelijskih linija dojk, Tumors are the second leading cause of death in the world (following cardiovascular diseases) and it is estimated that the incidence of tumors will increase in the future. Chemotherapy is one of the most common methods of tumor treatment which is often accompanied by systemic side effects. Treatment of tumors with one therapeutic agent often results in limited clinical outcome. Combination therapy, using a variety of agents and modalities of action, can synergistically increase thelevel of antitumor activity, lowering the dose of each single agent and thus reduce adverse side effects. The simultaneous application of various therapeutic agents requires a delivery platform to enable normalization of agents’ pharmacokinetics and pharmacodynamics. Because of its physico-chemical and biological activities,fullerenol C60(OH)24 represents a suitable platform for drug delivery. In the aqueous solution fullerenol is in the form of negatively charged polianionic nanoparticles (FNP) that possess a large surface area and have the ability of binding positively charged chemotherapeutic drug, such as doxorubicin (DOX), as well as positively charged metal ions, particularly Fe 2+ . The main biological activity of fullerenol is manifested through its antioxidant activity. In this study we used physico-chemical properties of fullerenol, doxorubicin and iron (Fe2+ ) in order to form stable fullerenol/doxorubicin (FNP/DOX) nanocomposite and fulerenol/iron (FNP/Fe 2+) nanocomposite. The nanocomposites were characterized by different physical- chemical methods which showed that FNP/DOX has particle size between 20 nm and 58 nm and charge of -6 mV, while FNP/Fe 2+ has particle size between 11 nm and 60 nm and charge of -30.8 mV. Both nanocomposites revealed discoidal morphology. The nanocomposites have also displeyed good stability in aqueous systems, which makethem biocompatible and suitable for use in biomedical applications. FNP decorated with DOX, in the form of FNP/DOX nanocomposite

Medonosna pčela (Apis mellifera Linnaeus, 1758) je široko rasprostranjena vrsta iz grupe socijalnih insekata, glavni oprašivač mnogih divljih biljaka i poljoprivrednih kultura. Pored njene primarne uloge u oprašivanju, koristi se i za dobijanje pčelinjih proizvoda, pre svega meda, voska i propolisa, čime se dodatno naglašava njen privredni značaj. Uzimajući u obzir značaj medonosne pčele, a sa druge strane aktuelan problem pada broja kolonija, postoji potreba za razumevanje uzroka i procenu rizika koji leže u osnovi ovog kompleksnog problema. Stoga, istraživanja u ovoj doktorskoj disertaciji obuhvataju praćenje biohemijskih i fizioloških parametara kod medonosne pčele kao pokazatelja stanja pčelinjih zajednica tokom letnjeg i zimskog perioda na staništima sa različitim antropogenim uticajem. U prvoj fazi istraživanja su izvedeni akutni laboratorijski testovi izlaganja medonosne pčele subletalnim dozama pesticida, tiakloprida i klotianidina, a dobijeni rezultati su ukazali na narušenu neurotransmisiju, na izmene u aktivnosti antioksidativnih enzima i redoks statusa u ćeliji, kao i na imunosupresiju. U drugoj fazi istraživanja su analizirane kolonije medonosne pčele sa različitih lokaliteta na području AP Vojvodine, sa primenom stacionarnog i migratornog tipa pčelarenja, tokom letnjeg i zimskog perioda, a dobijeni rezultati su ukazali na značajne razlike u biohemijskom odgovoru medonosne pčele u zavisnosti od starosti pčela, sezone godine i tipa pčelinjaka. Na osnovu rezultata prethodne dve faze istraživanja, izvršen je odabir uzoraka, kao i izbor parametara za treću fazu istraživanja, gde je praćeno stanje medonosne pčele iz stacionalnih pčelinjih zajednica, tokom letnjeg aktivnog perioda, kao i početkom i krajem zimskog perioda mirovanja pčela, sa tri lokaliteta u Republici Srbiji sa različitim stepenom urbanizacije i industrijalizacije: Beograd kao urbano, Susek kao ruralno i Zajača kao industrijsko područje. Dobijeni rezultati su ukaza, The honey bee (Apis mellifera Linnaeus, 1758) is a‚widespread social insect species and the main pollinator of various wild plants and agricultural crops.In addition to its primary role in pollination, the honey bee is also used for obtaining honeybee products, mostly honey, wax, and propolis, with a significant role in the economy. Number of honey bee colonies is declining, thus necessitating the assessment of underlying reasons and risks. Therefore, in this doctoral dissertation, biochemical and physiological parameters in the honey bee were monitored as indicators of the colonies’ condition during the summer and winter period in habitats with different anthropogenic impacts. In the first phase of the research, acute laboratory tests of honey bee exposure to sublethal doses of pesticides (thiacloprid and clothianidin) were performed and the obtained results indicated impaired neurotransmission, changes in the activity of antioxidant enzymes, and redox status in the cell, as well as immunosuppression. In the second phase of the research, honey bee colonies from different localities in the area of AP Vojvodina were analyzed, using the stationary and migratory types of beekeeping, during the summer and winter period, and the obtained results indicated significant differences in the biochemical response of the honey bee depending on the age of the bees, the season of the year, and the type of apiary. Based on the results of the previous two phases of the research, the selection of samples was performed, as well as the selection of parameters for analysis within the third phase of the research, where the condition of honey bees from stationary bee communities was monitored during the summer active period, as well as the beginning and end of winter dormancy of bees, from three localities in the Republic of Serbia with diffe