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Background/Aim. Exposure of living organisms to γ-radiation results in the overproduction of free radicals. The aim of the study was to test if the subacute administration of micronized zeolite (MZC) accomplishes radioprotective role based on the evaluation of the status of oxidative stress (OS) in the brain and 8-hydroxyguanosine (8-OH-dG) in the plasma of the rats exposed to the single γ-ray irradiation of 2 and/or 10 Gray (Gy). Methods. Wistar rats were on a four-week normal or 5% MZC supplemented diet and afterward exposed to the single γ-ray irradiation of 2 and 10 Gy. Groups of rats were: a) on a normal diet (the control group, and 2Gy and 10Gy groups); b) on 5% MZC supplemented diet (the control group – MZC, MZC + 2Gy, and MZC + 10Gy groups). We measured malondialdehyde (MDA), glutathione (GSH) total, and activity of total super-oxide dismutase (tSOD) and manganese superoxide dismutase (MnSOD) in vulnerable brain regions (cerebellum, hippocampus, and cerebral cortex) and 8-OH-dG in plasma. Results. Lower MDA was found in the MZC+2Gy and MZC+10Gy groups compared to the 2Gy and 10Gy groups. Activity od total SOD was higher in the MZC+10Gy group than in the 10Gy one. GSH was the highest in the 10Gy group. Compared to the control group, 8-OH-dG was extremely higher in groups radiated with 10 Gy regardless of a diet, but slightly lower in the MZC+2Gy and 2Gy groups. Conclusion. Subacute MZC pretreatment accomplished partial radioprotective effect in irradiated rats compared to non-irradiated rats, based on suppressed SOD activity at 2 Gy, and reduced brain MDA when exposed to 2 Gy and 10 Gy., Background/Aim. Exposure of living organisms to γradiation results in the overproduction of free radicals. The aim of the study was to test if the subacute administration of micronized zeolite (MZC) accomplishes radioprotective role based on the evaluation of the status of oxidative stress (OS) in the brain and 8-hydroxyguanosine (8-OH-dG) in the plasma of the rats exposed to the single γ-ray irradiation of 2 and/or 10 Gray (Gy). Methods. Wistar rats were on a four-week normal or 5% MZC supplemented diet and afterward exposed to the single γ-ray irradiation of 2 and 10 Gy. Groups of rats were: a) on a normal diet (the control group, and 2Gy and 10Gy groups); b) on 5% MZC supplemented diet (the control group – MZC, MZC + 2Gy, and MZC + 10Gy groups). We measured malondialdehyde (MDA), glutathione (GSH) total, and activity of total superoxide dismutase (tSOD) and manganese superoxide dismutase (MnSOD) in vulnerable brain regions (cerebellum, hippocampus, and cerebral cortex) and 8-OH-dG in plasma. Results. Lower MDA was found in the MZC+2Gy and MZC+10Gy groups compared to the 2Gy and 10Gy groups. Activity od total SOD was higher in the MZC+10Gy group than in the 10Gy one. GSH was the highest in the 10Gy group. Compared to the control group, 8-OH-dG was extremely higher in groups radiated with 10 Gy regardless of a diet, but slightly lower in the MZC+2Gy and 2Gy groups. Conclusion. Subacute MZC pretreatment accomplished partial radioprotective effect in irradiated rats compared to non-irradiated rats, based on suppressed SOD activity at 2 Gy, and reduced brain MDA when exposed to 2 Gy and 10 Gy.

Dental caries and periodontitis are among the most common health conditions that are currently recognized as growing socio-economic problems relating to their increasing prevalence, negative socio-economic impact, and harmful effects on systemic health. So far, the exact effects of caries and standard restorative materials on periodontal inflammatory and oxidative status are not established. The present study aimed to investigate the effect of caries and its restoration using standard temporary and permanent filling materials on a panel of 16 inflammatory and oxidative markers in gingival crevicular fluid (GCF) of periodontally healthy individuals, 7 (D7) and 30 (D30) days post-restoration, while the intact teeth represented the control. One hundred ninety systemically and periodontally healthy patients with occlusal caries underwent standard cavity preparation and restorations with one of six standard temporary or permanent restorative material according to indication and randomization scheme. Interleukin (IL)-2, IFN- g, IL-12, IL-17A, IL-13, IL-9, IL-10, IL-6, IL-5, IL-4, IL-22, TNF-a, IL1- b, thiobarbituric acid reactive substances, superoxide dismutase, and reduced form of glutathione were measured in GCF samples by flowcytometry and spectrophotometry in aid of commercial diagnostic assays. Caries affected teeth exhibited significantly increased IL-1 b, IL-17, IL- 22, and TBARS and decreased IL-9 concentrations compared to healthy controls. Treatment generally resulted in an increased antioxidant capacity with exception of zinc-polycarboxylate cement showing distinctive inflammatory pattern. Comparison of inflammatory and oxidative profiles in temporary and permanent restorations showed material-specific patterning which was particularly expressed in temporary materials plausibly related to greater caries extension. Caries affected teeth exhibited a balanced inflammatory pattern in GCF, with a general tendency of homeostatic re-establishment following treatment.

Background/Aim. Recent studies indicate that adipokines have an important role in bone physiology and pathology. Recent data indicate that adipokine leptin functions as a regulator of bone growth at multiple levels, systemically and locally. So far, it has been shown that leptin influences bone volume and bone mineral density in a population with metabolic and/or hormonal abnormality. Data concerning leptin values in non-obese children with fractures are scarce. Methods. This study included 93 non-obese children with long bone fractures (LBF), 14 children with short bone fractures (SBF), and 19 healthy children. Leptin concentration was determined in two blood samples (day 0 and day 21) and analyzed according to gender, fracture type, anatomical localization of the fracture, fracture topography, callus formation, and the healing outcome. Results. Children with LBF demonstrated significantly increased leptin levels compared to the control group (both day 0/day 21). In the control group, girls had significantly more leptin than boys. Leptin value was significantly influenced by anatomical localization since boys and girls with humerus fracture and girls with femur fracture had the highest average leptin concentration in the initial sample. Boys with incomplete callus formation had the highest leptin concentration (both day 0/day 21), significantly elevated compared to boys' samples in the control group, boys' samples with an intermediary and well-formed callus, and also increased compared to the initial samples of girls with incomplete callus. Better callus formation in girls was associated with an increment of leptin concentrations in the second over the initial sample. Girls with partially and satisfactorily formed callus had significantly increased leptin concentration in the second sample (day 21) compared to the boys' group. Conclusion. Leptin concentration was significantly increased (both samples) in children with LBF compared to children with SBF and correspon, Uvod/Cilj.Novijestudije pokazuju da adipokini imaju važnu ulogu u fiziologiji i patologiji kostiju. Takođe, najnoviji podaci pokazuju da adipokin leptin funkcioniše kao regulator rasta kostiju sistemski i lokalno. Pokazano je da leptin utiče na volumen kostiju i mineralnu gustinu kostiju u populaciji sa metaboličkom i/ili hormonskom abnormalnošću. Podaci o vrednostima leptina kod negojazne dece sa frakturama su oskudni. Metode. U ovu studijubil a su uključena93 negojazna deteta sa prelomima dugih kostiju (LBF), 14 dece sa prelomima malih kostiju (SBF) i 19 zdrave dece. Koncentracija leptina određena je u 2 uzorka krvi (0. danai 21 . dana) i analizirana prema polu, tipu frakture, lokalizaciji anatomske frakture, topografiji frakture, formiranju kalusa i ishodu zarastanja.Rezultati.Deca sa LBF imala su značajnopovećane nivoeleptina u poređenju sa kontrolnom grupom u oba uzorka krvi ( 0. dana/21 . dana). U kontrolnoj grupi devojčice su imale značajno više nivoe leptina od dečaka. Na vrednost leptina značajno je uticala anatomska lokalizacija, jer su dečaci i devojčice sa prelomom humerusa i devojčice sa prelomom femura imali najveću prosečnu koncentraciju leptina u početnom uzorku. Dečaci sa nepotpuno for miranim kalusom imali su najveću koncentraciju leptina (u oba uzorka, 0. dana/21. dana),značajno višuu odnosu na kontrolne uzorke dečaka, uzorke dečaka s intermedijarnim i dobro formiranim kalusom, a takođe višu u odnosu na koncentracije leptina u početnim uzorcima djevojčica s nepotpunim kalusom. Bolje formiranje kalusa kod devojčica je bilo povezano sa poveć anjem koncentracije leptina u drugom (21. dan) u odnosu na početni uzorak(0. dan). Devojčice sa delimično i zadovoljavajuće formiranim kalusom imale su značajno višu koncentraciju leptina u drugom uzorku (21. dan ) u odnosu na grupu dečaka. Zaključak. Koncentracija leptina je značajno povećana (u oba uzorkakrvi ) kod dece sa LBF u poređenju sa decom sa SBF i odgovarajućim kontrolama. Koncentracija leptina je zav

The initial steps in preclinical drug developing research concern the synthesis of new compounds for specific therapeutic use which needs to be confirmed by in vitro and then in vivo testing. Nine thiazolidinone derivatives (numerically labeled 1-9) classified as follows: 1,3-thiazole-based compounds (1 and 2); 1,3,4-thiadiazole based compounds (3 and 4); substituted 5-benzylideno-2-adamantylthiazol[3,2-b] [1,2,4] triazol-6(5H) ones (5-8); and an ethylaminothiazole-based chalcone (9), were tested for antioxidant activity (AOA) by using three in vitro assays: DPPH (1,1-diphenyl-2-picrylhydrazyl scavenging capacity test); FRAP (ferric reducing antioxidant power test); and TBARS (thiobarbituric acid reactive substances test). Compounds 1-4 and 9 in particular are newly synthesized compounds. Also, traditional antioxidants Vitamins E and C and alpha-lipoic acid (alpha-LA) were tested. The results of DPPH testing: Vitamin C 94.35%, Vitamin E 2.99% and alpha-LA 1.57%; compounds: 4 33.98%; 2 18.73%; 1 15.62%; 5 6.59%; 3 4.99%; 6-9 demonstrated almost no AOA. The results of TBARS testing (% of LPO inhibition): Vitamin C 62.32%; Vitamin E 36.29%; alpha-LA 51.36%; compounds: 1 62.11%; 5 66.71%; 9 60.93%; 4, 6 and 7 demonstrated similar to 50%; 3 and 8 displayed similar to 38%; 2 23.51%. By FRAP method, Vitamins E and C showed equal AOA, similar to 100%, unlike alpha-LA (no AOA), and AOA of the tested compounds (expressed as a fraction of the AOA of Vitamin C) were: 2 and 4-75%; 8, 3 and 1-45%; 5-7 and 9-27%. Different red-ox reaction principles between these assays dictate different AOA outcomes for a single compound. Vitamin C appeared to be the superior antioxidant out of the traditional antioxidants; and compound 4 was superior to other tested thiazolidinone derivatives. Vitamin C appeared to be the superior antioxidant out of the traditional antioxidants; and compound 4 was superior to other tested thiazolidinone derivatives. Phenyl-functionalized benzylidene, amino-carbo

Cortical theta burst stimulation (TBS) structured as intermittent (iTBS) and continuous (cTBS)could prevent the progression of the experimental autoimmune encephalomyelitis (EAE). The interplayof brain antioxidant defense systems against free radicals (FRs) overproduction induced by EAE,as well as during iTBS or cTBS, have not been entirely investigated. This study aimed to examinewhether oxidative-nitrogen stress (ONS) is one of the underlying pathophysiological mechanisms ofEAE, which may be changed in terms of health improvement by iTBS or cTBS. Dark Agouti strainfemale rats were tested for the effects of EAE and TBS. The rats were randomly divided into the controlgroup, rats specifically immunized for EAE and nonspecifically immuno-stimulated with CompleteFreund’s adjuvant. TBS or sham TBS was applied to EAE rats from 14th–24th post-immunizationday. Superoxide dismutase activity, levels of superoxide anion (O2•–), lipid peroxidation, glutathione(GSH), nicotinamide adenine dinucleotide phosphate (NADPH), and thioredoxin reductase (TrxR)activity were analyzed in rat spinal cords homogenates. The severity of EAE clinical coincided withthe climax of ONS. The most critical result refers to TrxR, which immensely responded against theapplied stressors of the central nervous system (CNS), including immunization and TBS. We foundthat the compensatory neuroprotective role of TrxR upregulation is a positive feedback mechanismthat reduces the harmfulness of ONS. iTBS and cTBS both modulate the biochemical environmentagainst ONS at a distance from the area of stimulation, alleviating symptoms of EAE. The results ofour study increase the understanding of FRs’ interplay and the role of Trx/TrxR in ONS-associatedneuroinflammatory diseases, such as EAE. Also, our results might help the development of new ideasfor designing more effective medical treatment, combining neuropsychological with noninvasiveneurostimulation–neuromodulation techniques to patients living with MS.

Biocompatibility of dental materials (DM) can be evaluated by gingival crevicular fluid (GCF) oxidative stress (OS) status. The goal of the study was to ascertain influence of dental caries degree, teeth position, and type and amount of applied DM on GCF OS profile. For this purpose, we tested six DMs that were sealed in one session: amalgam (Amg), composites: Tetric EvoCeram and Beautifil (BF), phosphate cement-zinc phosphate and polycarboxylate cements zinc polycarboxylate cements, and glass ionomer cement (GIC). The study included 88 dental outpatients. Follow-up was scheduled at 7th and 30th day. Oxidative stress parameters (malondialdehyde (MDA) and glutathione (GSH) levels and total superoxide dismutase (tSOD) activity) were measured before (0th day) and after the treatment (7th and 30th day) in GCF. Control teeth were mirror-positioned healthy teeth. The DM accomplished the following effects (listed in descending order): increase of GSH in GCF was realized by ZPoC > BF > GIC > Amg; tSOD activity increase by ZPoC > BF > Amg; and MDA decrease by ZPoC > ZPhC > Amg > TEC. Dental caries provokes insignificant rise of OS in GCF. ZPoC and ZPhC showed the highest antioxidant effect, contrary to GIC. Restorations with antioxidant properties may reduce gum diseases initiated by caries lesion, what is of great clinical relevance in dentistry.

The aim of our study was to test the effect of subacutely applied micronized zeolite [micronized clinoptilolite (MZC)] on brain status of iron (Fe), reactive oxygen and nitrogen species (ROS, RNS), and radioprotective role against brain oxidative/nitrosative stress (OS/NS) initiated by single ionizing radiation of 2 or 10Gray (Gy). Wistar rats on normal (n=18) and 5% MZC supplemented diet (n=18), during 4 weeks, were internally subdivided into 3 subgroups (6 rats in each subgroup), with one of subgroup remaining as a control, and the other two subjected to single ionizing radiation of 2Gy or 10Gy. Thus, we had groups on normal diet: C – controls, 2Gy and 10Gy; and on 5% MZC supplemented diet: MZC, MZC+2Gy and MZC+10Gy. Concentrations of nitrates (a final RNS metabolite) and superoxide anion radical (O2 •-) (an initial ROS) were measured in homogenates of selective vulnerable brain regions (cerebellum, hippocampus and forebrain cortex), while Fe was determined in whole brain of rats. Results documented a significant drop of Fe in MZC and MZC+2Gy/10Gy groups; decrease of O2 •- and nitrate in MZC group; almost equal drop of O2 •- , in 2Gy and MZC+2Gy groups; and nitrate increase in 10Gy and MZC+10Gy groups. We confirmed that subacute MZC pretreatment contributes to partially accomplished brain radioprotective effect in rats exposed to single radiation dose of 2Gy and 10Gy, probably due to reduced OS/NS and Fe.

Uvod: Melanom nastaje usled maligne transformacije melanocita i dominantno se javlja u koži, ali se može razviti i u sluznici, oku i u bilo kojem tkivu koje sadrži melanocite. Predstavlja najređi oblik malignih tumora kože, ali i najagresivniji jer je odgovoran za 60% smrtnih ishoda povezanih sa malignim tumorima kože. Glavni ciljevi ove studije bili su ispitati korelaciju serumskih vrednosti IL27 i vrednosti parametara oksidativnog stresa (tSOD, MnSOD, CAT, MDA i O2•–) sa kliničko-patološkim karakteristikama melanoma, kao i ispitati međusobnu povezanost koncentracija IL27 i vrednosti parametara oksidativnog stresa. Pacijenti i metode: U studiju je bilo uključeno 72 ispitanika sa dijagnozom melanoma, prosečne starosti oko 50 godina i 30 zdravih ispitanika. Koncentracija IL27 je određivana metodom ELISA testa, dok su parametri oksidativnog stresa određivani spektrofotometrijskim metodama. Rezultati: Rezultati ovog istraživanja pokazuju da su pacijenti sa melanom imali značajno povećanu produkciju O2•– i nivo markera oksidativnog stresa tj. MDA u odnosu na zdrave osobe, kao i izmenjen mehanizam antioksidativne zaštite (aktivnosti tSOD i MnSOD se nisu razlikovale između kontrolne grupe i obolelih od melanoma, dok je aktivnost SAT bila značajno veća kod obolelih od melanoma). Takođe, pokazano je da koncentracija IL27 značajno veća u serumu zdravih osoba u odnosu na obolele od melanoma. Pokazano je da je interleukin 27 dobar marker bolesti, dok su: O2•-, MDA i CAT osrednje dobri markeri bolesti. Takođe, pokazana je negativna korelacija između sledećih parametara: IL27 i CAT, IL27 i tSOD, IL27 i MnSOD. Zaključak: Dobijeni rezultati ukazuju na moguću protektivnu ulogu IL27 u bolesnika sa melanomom, što može biti korisno za razumevanje efekata IL27 i ukazati na mogućnost upotrebe ovog citokina u imunoterapiji. Praćenje parametra oksidativnog stresa može biti korisno u proceni stepena razvoja oksidativnog stresa i statusa antioksidativne odbrane u funkciji progresije melanom, Introduction: Melanoma is caused by malignant transformation of melanocytes and predominantly occurs in the skin, but can also develop in the mucous membrane, in the eye and in any tissue containing melanocytes. It is the rarest form of malignant skin tumors, but also the most aggressive because it is responsible for 60% of deaths associated with malignant skin tumors. The main objectives of this study were to examine the correlation of serum IL27 values and the values of oxidative stress parameters (tSOD, MnSOD, CAT, MDA and O2•-) with clinical-pathological characteristics of melanoma, as well as to examine the interconnectedness of IL27 concentrations and the values of oxidative stress parameters. Patients and methods: The study included 72 subjects with a diagnosis of melanoma, an average age of 50 years and 30 healthy subjects. The IL27 concentration was determined by the ELISA test method, while the parameters of oxidative stress were determined by spectrophotometric methods. Results: The results of this study show that patients with melanoma had a significantly increased production of O2•- and level of MDA (markers of oxidative stress), compared to healthy controls, as well as the modified antioxidant mechanism (the activities of tSOD and MnSOD were not different between control group and melanoma patients, while CAT activity was significantly higher in melanoma patients). It has also been shown that the concentration of IL27 is significantly higher in the serum of healthy individuals compared to melanoma patients. Interleukin 27 has been shown to be a good marker of the disease, while: O2•-, MDA and CAT are the moderately good markers of the disease. Also, it has been shown a negative correlation between the following parameters: IL27 and CAT, IL27 and tSOD, IL27 and MnSOD. Conclusion: The obtained results indicate the possible protective role of IL27 in patients with melanoma, which can be useful for understanding the effects of IL27 and to indicate the poss

The objective of this prospective follow-up trial was to ascertain whether the urinary kidney injury molecule-1 (uKIM-1) associates with tumor tissue (tKIM-1) expression and with the pathological characteristics of clear renal cell carcinoma (cRCC) in radically nephrectomized (RN) and/or in partially nephrectomized (PN) patients with cRCC, pre- and postoperatively. This clinical study included 40 patients subjected to RN/PN (cRCC group) and 30 healthy volunteers (control group). Urinary KIM-1 was determined by ELISA TIM-1/KIM-1 kit and normalized by urinary creatinine. Immunohistochemical staining (monoclonal anti-human anti-TIM-1/KIM-1/HAVCR antibody) was used for semiquantitative analysis of the tKIM-1 expression and expressed as a score (% KIM-1 positively stained tubules). Both markers were interpreted in terms of the tumor characteristics comprising tumor size, Fuhrman grade, pathological (pT) stage, tumor/nodes/metastasis (TNM) stage, lymphovascular invasion and type of surgery RN/PN. Preoperative uKIM-1 was significantly higher in the cRCC group compared to controls, such as uKIM-1 was statistically higher in RN than in PN patients. Postoperatively, uKIM-1 decreased to control values. Expression of tKIM-1 was documented in all nephrectomized patients. Significant associations were achieved between uKIM-1 and tKIM-1 and with considered tumor characteristics, especially with tumor size and grade. Based on the accomplished associations, we found uKIM-1 as a highly sensitive marker for cRCC diagnosis. The clinical trial registration number: 1110-2012.

Background: Overproduction of free radicals accompanied with their insufficient removal/neutralization by antioxidative defense system impairs redox hemostasis in living organisms. Oxidative stress has been shown to be involved in all the stages of carcinogenesis and malignant melanocyte transformation. The aim of this study was to examine association between oxidative stress development and different stages of melanoma. Methods: The measured oxidative stress parameters included: superoxide anion radical, total and manganese superoxide dismutase, catalase and malondialdehyde. Oxidative stress parameters were measured spectrophotometrically in serum samples from melanoma patients (n=72) and healthy control subjects (n=30). Patients were classified according to AJCC clinical stage. Results: Average superoxide anion and malondialdehyde concentrations were significantly higher in melanoma patients than in control group, with the highest value of superoxide anion in stage III, while malondialdehyde highest value was in stage IV. The activity of total and manganese superoxide dismutase was insignificantly higher in melanoma patients than in control group, while catalase activity was significantly higher. The highest activity of total superoxide dismutase was in stage III, while the highest activity of manganese superoxide dismutase was in stage IV. Catalase activity was increasing with the disease progression achieving the maximum in stage III. Conclusions: Results of our study suggest that melanoma is oxidative stress associated disease, as well as deteriorated cell functioning at mitochondrial level.

Mehanizmi hepatotoksičnog efekta individualne i paralelne izloženosti organizma kadmijumu (Cd) i/ili etanolu su dovoljno ispitani, dok efekti disulfirama (DSF) na jetru nakon prethodne izloženosti organizma Cd i/ili etanolu, kao i tokom koekspozicije sa Cd, nisu istraženi. Imajući u vidu da je duvanski dim značajan izvor izloženosti Cd, zatim, da su alkoholičari uglavnom i pušači, te da je averzivna terapija DSF dio realnog scenarija liječenja alkoholizma, cilj ove studije je bio da se ispitaju efekti individualne izloženosti DSF na redoks status (posebno u domenu glutationskog ciklusa), status esencijalnih metala i funkciju jetre, kao i na status jetre nakon prethodne izloženosti organizma Cd i/ili etanolu, kao i tokom koekspozicije sa Cd, iz razloga što ovi pacijenti nastavljaju sa pušenjem cigareta tokom terapije DSF, dok je unos alkohola ukinut. Rasvjetljavanje interferencije sulfhidrilne (–SH) grupe metabolita DSF sa antioksidativnim odgovorom glutationskog ciklusa, kao i statusom metala u jetri u datim eksperimentalnim uslovima bio je fokus ovog istraživanja, što je od značaja ako uzmemo u obzir da i Cd i etanol, kao i izmijenjeni status esencijalnih metala remete redoks metabolizam, odnosno mijenjaju glutationski status u jetri. Analitika simultanog određivanja redukovanog i oksidovanog oblika glutationa (GSH i GSSG) iz homogenata jetre tretiranih pacova, primjenom visoko efikasne tečne hromatografije uz UV detekciju (HPLC-UV), bio je dodatni cilj ove disertacije. Sprovedena animalna studija (na pacovima Wistar soja, mužjacima, n = 210) imala je za cilj da imitira okolnosti alkoholičara-pušača prije i tokom primjene DSF i trajala je za pojedine eksperimentalne grupe 21, odnosno 42 dana. Etanol, DSF i maslinovo ulje (OlO) kao rastvarač za DSF, su davani oralnim putem (gavažom), a Cd intraperitonelano, na dnevnoj bazi. Oformljene eksperimentalne, kao i kontrolne grupe imala su podgrupe, shodno terminima žrtvovanja pacova (1, 3, 10, 21 i 42 dana), navedenih u u, Mechanisms involved in genesis of hepatotoxic effects following individual and parallel exposure to cadmium (Cd) and/or ethanol, are thoroughly investigated. However, the effects of disulfiram (DSF) introduced to treatment following exposure to Cd and/or ethanol were not formerly presented in studies. While conducting the study it was taken into consideration that cigarette smoke is a significant source of Cd exposure, as well as that alcoholics are most likely smokers, and also that aversive therapy with DSF is a real life scenario in alcohol dependence treatment. The aim of the study was to investigate the effects of individual exposure to DSF related to redox status (particularly in domain of glutathione cycle), essential metals status and liver function, as well as the status following exposure to Cd and/or ethanol and also during co-exposure with Cd, considering that patients undergoing DSF treatment continue with heavy smoking, whilst alcohol intake is excluded. The focus of the study was set on elucidation of possible interference of the free thiol (–SH) group of DSF metabolite and antioxidant glutathione response, as well as essential metals status under specified experimental conditions. Additionally, Cd and ethanol, along with changed essential metals status affect glutathione homeostasis in the liver. Both glutathione forms, reduced and oxidized (GSH and GSSG), were measured by high performance liquid chromatography method with UV detection (HPLC-UV). The conducted animal study (male Wistar rats, n = 210) aimed to mimic circumstances in the liver of alcoholics-smokers before and during DSF treatment, with defined duration of 21 or 42 days for different experimental groups. Ethanol, DSF and olive oil (OlO), used as DSF solvent, were daily administered orally (via gavage), whilst Cd was administered intraperitoneally. Each of defined experimental and control groups was divided, according to the chosen time of exposure (1, 3, 10, 21 and 42 days), in subgroup

Dosadašnja istraživanja mehanizama toksičnosti alkohola i kadmijuma (Cd) pri pojedinačnoj i udruženoj izloženosti eksprimantalnih životinja potvrđuju da oba agensa dovode do reproduktivne toksičnosti. Brojne epidemiološke studije su takođe ukazale da su pušenje i alkoholizam uzročnici poremećaja u spermatogenezi i neplodnosti kod muškaraca. S obzirom na činjenicu da je duvanski dim značajan izvor izloženosti Cd, kao i da su alkoholičari uglavnom i pušači, potrebno je utvrditi kako disulfiram (DSF), lek koji se koristi u averzivnoj terapiji alkoholizma, utiče na reproduktivnu toksičnost izazvanu pomenutim toksikantima. Cilj ove studije je bio da se ispita efekat DSF na narušenu homeostazu bioelemenata, redoks i androgeni status u testisima pacova prethodno izloženih alkoholu i/ili Cd kao i tokom koekspozicije sa Cd. Slobodna sulfhidrilna grupa (–SH) u hemijskoj strukturi metabolita DSF, dietilditiokarbamata (DDTC), ukazuje na redukcioni i helirajući potencijal DSF koji umnogome može da promeni metabolizam kako ispitivanih toksičnih agenasa (alkohola i Cd), tako i esencijalnih bioelemenata, kao i endogenih jedinjenja koja poseduju –SH grupe zbog mogućih reakcija tiolnog ukrštanja. Studija na životinjama (mužjaci pacova Wistar soja, n = 288) je dizajnirana sa ciljem da se imitiraju navike alkoholičara-pušača pre i nakon uvođenja DSF. Životinje su bile izložene ispitivanim supstancama subakutno (alkoholu i DSF), odnosno subhronično (Cd). Alkohol, DSF i maslinovo ulje (MU) kao rastvarač za DSF, su davani putem oralne sonde (per os), a Cd intraperitonelano (i.p.), svakodnevno u jednoj dozi. Životinje su slučajnim odabirom podeljene na kontrolne grupe i 7 eksperimentalnih grupa, od kojih je svaka grupa podeljena u 4 ili 6 podgrupa (n = 6) u odnosu na dužinu izloženosti svakoj od ispitivanih supstanci pojedinačno ili njihovoj kombinovanoj primeni. Podela eksperimentalnih životinja na grupe u odnosu na trajanje ekspozicije (1, 3, 10, 21 i 42 dana) je sledeća: tri kontrolne g, Previous animal studies on the mechanisms of toxicity after exposure or co-exposure to alcohol and cadmium (Cd) confirmed that both agents induce reproductive toxicity. Numerous epidemiological studies have also suggested that smoking and alcoholism cause disturbances in spermatogenesis and infertility in men. Due to the fact that tobacco smoke is an important source of Cd exposure, as well as alcoholics are usually smokers too, it is necessary to determine if disulfiram (DSF), a drug used in aversive therapy of alcoholism, affects the reproductive toxicity induced by the abovementioned toxicants. The aim of this study was to examine the effect of DSF on disturbed bioelements’ homeostasis, redox and androgen status in the testes of rats previously exposed to alcohol and / or Cd and during co-exposure with Cd. Free sulfhydryl group (-SH) in the chemical structure of the DSF’s metabolite, diethyldithiocarbamate (DDTC), indicates the reducing and chelating potential of DSF, which in many ways can change the metabolism of tested toxic agents (A and Cd), as well as essential bioelements, and endogenous compounds containing -SH groups due to possible reactions of thiol linking. The animal study (male Wistar rats, n = 288) was designed in order to imitate the conditions of alcoholics-smokers before and after the introduction of DSF. The animals were exposed to the tested substances subacute (alcohol and DSF) and subchronic (Cd). Alcohol, DSF, and olive oil (OL), as a solvent for DSF, were administered via oral gavage (per os), and Cd intraperitoneally, in a single daily dose. Animals were randomly divided into control groups and 7 experimental groups, each group was divided into 4 or 6 subgroups (n = 6) according to the duration of exposure to the tested substances alone or in combination. The division of the groups of the experimental animals with respect to the exposure time (1, 3, 10, 21 and 42 days) was as follows: three control groups (C1-42, OL1-21 and C1-21 / OL22-4

Dosadašnja istraživanja mehanizama toksičnosti alkohola i kadmijuma (Cd) pri pojedinačnoj i udruženoj izloženosti eksprimantalnih životinja potvrđuju da oba agensa dovode do reproduktivne toksičnosti. Brojne epidemiološke studije su takođe ukazale da su pušenje i alkoholizam uzročnici poremećaja u spermatogenezi i neplodnosti kod muškaraca. S obzirom na činjenicu da je duvanski dim značajan izvor izloženosti Cd, kao i da su alkoholičari uglavnom i pušači, potrebno je utvrditi kako disulfiram (DSF), lek koji se koristi u averzivnoj terapiji alkoholizma, utiče na reproduktivnu toksičnost izazvanu pomenutim toksikantima. Cilj ove studije je bio da se ispita efekat DSF na narušenu homeostazu bioelemenata, redoks i androgeni status u testisima pacova prethodno izloženih alkoholu i/ili Cd kao i tokom koekspozicije sa Cd. Slobodna sulfhidrilna grupa (–SH) u hemijskoj strukturi metabolita DSF, dietilditiokarbamata (DDTC), ukazuje na redukcioni i helirajući potencijal DSF koji umnogome može da promeni metabolizam kako ispitivanih toksičnih agenasa (alkohola i Cd), tako i esencijalnih bioelemenata, kao i endogenih jedinjenja koja poseduju –SH grupe zbog mogućih reakcija tiolnog ukrštanja.Studija na životinjama (mužjaci pacova Wistar soja, n = 288) je dizajnirana sa ciljem da se imitiraju navike alkoholičara-pušača pre i nakon uvođenja DSF. Životinje su bile izložene ispitivanim supstancama subakutno (alkoholu i DSF), odnosno subhronično (Cd). Alkohol, DSF i maslinovo ulje (MU) kao rastvarač za DSF, su davani putem oralne sonde (per os), a Cd intraperitonelano (i.p.), svakodnevno u jednoj dozi. Životinje su slučajnim odabirom podeljene na kontrolne grupe i 7 eksperimentalnih grupa, od kojih je svaka grupa podeljena u 4 ili 6 podgrupa (n = 6) u odnosu na dužinu izloženosti svakoj od ispitivanih supstanci pojedinačno ili njihovoj kombinovanoj primeni. Podela eksperimentalnih životinja na grupe u odnosu na trajanje ekspozicije (1, 3, 10, 21 i 42 dana) je sledeća: tri kontrolne gr, Previous animal studies on the mechanisms of toxicity after exposure or co-exposure to alcohol and cadmium (Cd) confirmed that both agents induce reproductive toxicity. Numerous epidemiological studies have also suggested that smoking and alcoholism cause disturbances in spermatogenesis and infertility in men. Due to the fact that tobacco smoke is an important source of Cd exposure, as well as alcoholics are usually smokers too, it is necessary to determine if disulfiram (DSF), a drug used in aversive therapy of alcoholism, affects the reproductive toxicity induced by the abovementioned toxicants. The aim of this study was to examine the effect of DSF on disturbed bioelements’ homeostasis, redox and androgen status in the testes of rats previously exposed to alcohol and / or Cd and during co-exposure with Cd. Free sulfhydryl group (-SH) in the chemical structure of the DSF’s metabolite, diethyldithiocarbamate (DDTC), indicates the reducing and chelating potential of DSF, which in many ways can change the metabolism of tested toxic agents (A and Cd), as well as essential bioelements, and endogenous compounds containing -SH groups due to possible reactions of thiol linking.The animal study (male Wistar rats, n = 288) was designed in order to imitate the conditions of alcoholics-smokers before and after the introduction of DSF. The animals were exposed to the tested substances subacute (alcohol and DSF) and subchronic (Cd). Alcohol, DSF, and olive oil (OL), as a solvent for DSF, were administered via oral gavage (per os), and Cd intraperitoneally, in a single daily dose. Animals were randomly divided into control groups and 7 experimental groups, each group was divided into 4 or 6 subgroups (n = 6) according to the duration of exposure to the tested substances alone or in combination. The division of the groups of the experimental animals with respect to the exposure time (1, 3, 10, 21 and 42 days) was as follows: three control groups (C1-42, OL1-21 and C1-21 / OL22-42

Examination of cadmium (Cd) toxicity and disulfiram (DSF) effect on liver was focused on oxidative stress (OS), bioelements status, morphological and functional changes. Male Wistar rats were intraperitoneally treated with 1mg CdCl2/kg BW/day; orally with 178.5 mg DSF/kg BW/day for 1, 3, 10 and 21 days; and co-exposed from 22nd to 42nd day. The co-exposure nearly restored previously suppressed total superoxide dismutase (SOD), catalase (CAT) and increased glutathione peroxidase (GPx) activities; increased previously reduced glutathione reductase (GR) and total glutathione-S-transferase (GST) activities; reduced previously increased superoxide anion radical (O-2(center dot-)) and malondialdehyde (MDA) levels; increased zinc (Zn) and iron (Fe), and decreased copper (Cu) (yet above control value), while magnesium (Mg) was not affected; and decreased serum alanine aminotransferases (ALT) levels. Histopathological examination showed signs of inflammation process as previously demonstrated by exposure to Cd. Overall, we ascertained partial liver redox status improvement, compared with the formerly Cd-induced impact.

Introduction: The significance of oxidative stress in pathogenesis of childhood asthma was recognized, but its role in the clinical manifestations of disease is still unclear. Materials and Methods: The study was conducted in 96 asthmatic children. The urinary biomarker of oxidative stress, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG/creatinine) was determined by using HPLC-MS/MS. ELISA was performed to measure myeloperoxidase (MPO) and Cu,Zn-superoxide dismutase (Cu, Zn-SOD) in serum. Results: Logistic regression analysis revealed that female gender, tobacco smoke exposure, and increased 8-oxodG/creatinine were associated with risk for intermittent asthma, while the positive allergy test and increased Cu, Zn-SOD were associated with eczema in asthmatic children. Higher MPO (p = 0.033), and percent of granulocytes (p = 0.030) were found in severe persistent asthma in comparison to intermittent or mild persistent asthma. Conclusion: The main findings that TSE-induced oxidative stress is a risk for intermittent asthma and eczema may be clinically significant for the disease prevention and therapeutic improvements.

The aim of the study was to investigate if alcohol and disulfiram (DSF) individually and in combination affect bioelements' and red-ox homeostasis in testes of the exposed rats. The animals were divided into groups according to the duration of treatments (21 and/or 42 days): C-21/C-42 groups (controls); OL21 and OL22-42 groups (0.5 mL olive oil intake); A(1-21) groups (3 mL 20% ethanol intake); DSF1-21 groups (178.5 mg DSF/kg/day intake); and A(21)+DSF22-42 groups (the DSF ingestion followed previous 21 days' treatment with alcohol). The measured parameters in testes included metals: zinc (Zn), copper (Cu), iron (Fe), magnesium (Mg) and selenium (Se); as well as oxidative stress (OS) parameters: superoxide anion radical (O-2(center dot-)), glutathione reduced (GSH) and oxidized (GSSG), malondialdehyde (MDA), hydrogen peroxide (H2O2) decomposition and activities of total superoxide dismutase (tSOD), glutathione-Stransferase (GST) and glutathione reductase (GR). Metal status was changed in all experimental groups (Fe rose, Zn fell, while Cu increased in A(21)+DSF24-32 groups). Development of OS was demonstrated in A(1-21) groups, but not in DSF1-21 groups. In A(21)+DSF22-42 groups, OS was partially reduced compared to A groups (A(1-21)>MDA>C; A(1-21) lt GSH lt C). High metal-binding affinity of DSF/DDTC changes red-ox homeostasis in rat testes.

This study reports the synthesis of new 2H-chromene or coumarin based acylhydrazones, which were evaluated for their in vitro antimycobacterial activity against reference strain Mycobacterium tuberculosis H37Rv and compared to the first-line antituberculosis drugs, isoniazid (INH) and ethambutol (EMB). The most active compounds 7m (MIC 0.13 mu M), 7o (MIC 0.15 mu M) and 7k (MIC 0.17 mu M) demonstrated antimycobacterial activity at submicromolar concentration level and remarkably minimal associated cytotoxicity in the human embryonic kidney cell line HEK-293T. Structure-activity relationship for this class of compounds has been established.

The aim of our work was to optimize and apply simple high-performance liquid chromatography method with ultraviolet detection (HPLC-UV) for simultaneous determination of reduced (GSH) and oxidized (GSSG) glutathione in biological matrix (specifically, the rat liver tissue was used herein), since the ratio between oxidized and reduced glutathione forms (GSSG-GSH) has been recognized as an important biological marker of oxidatively depleted GSH in oxidative stress (OS)-associated diseases and poisonings. An isocratic chromatographic separation of GSH and GSSG (2.8 min and 6.3 min, respectively) was performed with the mobile phase consisted of sodium perchlorate solution (pH adjusted to 2.8) at flow rate of 1 mL min(-1), detection set at 215 nm, and column temperature of 40 degrees C. The method offers short run time, linearity in the range of 0.01-200 mu M concentration for both compounds (R-2 = 1), low limits of detection and quantification (GSH: 0.18 mu M and 0.56 mu M, GSSG: 0.52 mu M and 1.58 mu M, respectively), precision, accuracy (bias lt 2%), and high reproducibility. Through suitable sample handling, an overestimation of GSSG was prevented. High recovery (>99%) was achieved. The method was successfully applied for the analysis of GSH and GSSG in liver homogenates of Wistar rats intraperitoneally exposed to cadmium (Cd) (1 mg kg(-1) CdCl2/21 days). Regardless of other Cd-mediated hepatotoxicity mechanisms, herein, we have exclusively interpreted/emphasized oxidative GSH depletion. The presented method is acceptable for a routine analysis of GSH and GSSG in biological matrix, while the calculated ratio GSSG-GSH is considered as a valuable OS marker.

Most commonly observed central nervous system (CNS) effects induced by systemic toxicity of herbicide diquat (DQ) are general depression and lethargy. Generally, it is accepted that DQ exerts its toxicity through the production of superoxide anion radical (O2 ●-) during its redox metabolism in the presence of molecular oxygen, which further initiates radical chain reaction, contributing developing of oxidative stress (OS) as well. Mechanisms of DQ neurotoxic effect is not rationalized till now. The objective of the study was to examine whether OS contributes to DQ neurotxicity. For this purpose, male Wistar rats were intrastriataly (i.s.) treated with DQ and oxidative status parameters such as: superoxide anion radical (O2 ●-); nitrates (NO3 -), as a final metabolite of reactive nitogen species; malondialdehyde (MDA), an indicator of lipid peroxidation; activity of superoxide dismutase (SOD); glutathione peroxidase (GPx), and glutathione (GSH), were measured in the hippocampus at 30 minutes, 24 hours and 7 days post treatment. Noteworthy, mortality rate (30 - 40 %) was observed in the group of rats treated with DQ, within 2-3 hours after awakening from anesthesia. Additionally, lethargy was the only neurological symptom observed in that group. Analyzed parameters indicate that OS mediates DQ neurotxicity, which is documented with significant increase of lipid peroxidation., Najčešće zapaženi efekti sistemskog trovanja herbicidom dikvatom (DK) na centralni nervni sistem (CNS) su opšta depresija i letargija. Opšte je prihvaćeno da se toksičnost DK ostvaruje posredstvom povećanog stvaranja superoksid anjon radikala (O2 ●-) tokom njegovog redoks metabolizma, u prisustvu molekularnog kiseonika, koji dalje inicira lančanu reakciju radikalskog tipa i razvoj oksidativnog stresa (OS). Do danas mehanizmi neurotoksičnog efekta DK nisu u potpunosti poznati. Cilj ove studije je bio da ispitamo da li OS posreduje u neurotoksičnosti indukovanoj DK. Eksperiment je sproveden na mužjacima Wistar pacova, intrastrijatalno tretiranih (i.s.) DK. Parametri oksidativnog statusa, kao što su: superoksid anjon radikal (O2 ●-), nitrati (NO3 -), kao finalni metaboliti reaktivnih vrsta azota; malondialdehid (MDA), indikator lipidne peroksidacije; aktivnost enzima; superoksid dizmutaze (SOD) i glutation peroksidaze (GPx); i glutation (GSH) mereni su u hipokampusu, 30 minuta, 24 sati i 7 dana posle tretmana. Stopa smrtnosti od 30 do 40 % ustanovljena je u grupi pacova tretiranih DK, tokom 2-3 sata od buđenja iz anestezije. Dodatno, pacovi ove grupe su pokazali neurološke simptome letargije. Značajno povećana lipidna peroksidacija pokazuju da OS posreduje u neurotoksičnom odgovoru indukovanom i.s. primenom DK.