Papers by Ivana Stojanovic
Suppression of the lipid peroxidation process in the CNS reduces neurological expression of exper... more Suppression of the lipid peroxidation process in the CNS reduces neurological expression of experimentally induced autoimmune encephalomyelitis S Sr rd dj ja an n L Lj ju ub bi is sa av vl lj je ev vi ic c 1 1, ,2 2 , , I Iv va an na a S St to oj ja an no ov vi ic c 3 3 , , D Du us si ic ca a P Pa av vl lo ov vi ic c 3 3 , , M Ma aj ja a M Mi il lo oj jk ko ov vi ic c 2 2 , , D Du us sa an n S So ok ko ol lo ov vi ic c 3 3 , , I Iv va an na a S St te ev va an no ov vi ic c 4 4 , , A Al le ek ks sa an nd da ar r P Pe et tr ro ov vi ic c 5 5
Acta Medica Medianae, Sep 15, 2016
Colorectal cancer is one of the most frequent neoplastic diseases in the human population, and on... more Colorectal cancer is one of the most frequent neoplastic diseases in the human population, and one of the most frequent causes of death. Reactive oxygen species (ROS) are involved in the process of cancer initiation and progression. It is known that ROS are formed in excess in chronic diseases of the gastrointestinal tract, but the precise mechanisms of oxidative stress being induced in cancer cells and the role of ROS in colorectal cancer progression are still not exactly understood. Tumor tissue specimens as well the healthy colon tissue and the tissue surrounding the tumor were obtained from 50 primary colorectal cancers. The concentration of TBARS in the homogenate was determined by spectrophotometric method by Andreeva et al. AOPP concentrations in the tissue was measured by the spectrophotometric method by Vitko et al. Catalase activity in plasma was determined by spectrophotometric method by Goth. TBARS and AOPP levels were significantly higher in the tumor tissue compared to the control healthy tissue (p<0.001). Also, the tissue surrounding the tumor had higher concentration of TBARS and AOPP compared to the control healthy tissue (p<0.001). The activity of catalase in tumor tissue was significantly lower in comparison to the healthy colon tissue (p<0.001). This study defines that colorectal carcinogenesis is associated with serious oxidative stress and proves the involvement of lipid peroxidation and oxidative modification of proteins in malignant process and the spread of lipid peroxidation from malignant into the adjacent non-malignant colon tissue. The results also show a lower activity of catalase confirming the relevance of oxidative-antioxidative disorders.
Neurotoxicity Research, Jun 13, 2016
Although current evidence mainly suggests immunopathogenesis of demyelination and neurodegenerati... more Although current evidence mainly suggests immunopathogenesis of demyelination and neurodegeneration in multiple sclerosis (MS), there are results which document the importance of other factors, such as oxidative stress and its mediated injuries. The oxidative stress intensity in axonal damage during acute demyelination is little known. We performed this study as a cross-sectional biomarker validation study in order to evaluate the parameters of axonal damage (phosphorylated neurofilaments heavy chain (pNF-H)) and oxidative stress (8-hydroxy-2′-deoxyguanosine (8-OHdG)) in plasma of patients with initial and relapsing-remitting demyelination attacks, defined as clinically isolated syndrome (CIS) and relapsing-remitting multiple sclerosis (RRMS); and the correlations between these parameters and biological (index of blood brain barrier (BBB) permeability), clinical (index of disease progression), and radiological (T1-Gd-enhancing lesion volume) activities of disease. Both parameters were increased in CIS and RRMS compared to control subjects (p < 0.05). The positive correlations were observed between 8-OHdG values and index of BBB permeability, clinical severity of disease, and demyelinated brain lesion volume, in CIS group (r > 0.50; p < 0.05). Similar correlations were obtained between pNF-H values and the above parameters, as well as the index of disease progression, in RRMS group (r > 0.30; p < 0.05). There was a significant correlation between values of 8-OHdG and pNF-H only in CIS group, r = 0.52, p < 0.05. While the plasma values of 8-OHdG reflect the degree of acute demyelination in CIS, pNF-H values reflect that in RRMS. The obtained results must be reevaluated in similar prospective studies related to their prognostic values.
Frontiers in Aging Neuroscience, May 18, 2023
Introduction: Intracerebroventricularly (icv) injected streptozotocin (STZ) is a widely used mode... more Introduction: Intracerebroventricularly (icv) injected streptozotocin (STZ) is a widely used model for sporadic Alzheimer's disease (sAD)-like pathology, marked by oxidative stress-mediated pathological progression. Intermittent theta burst stimulation (iTBS) is a noninvasive technique for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for several neurological diseases, including AD. The present study aims to investigate the effect of the iTBS protocol on the animal model of STZ-induced sAD-like pathology in the context of antioxidant, anti-inflammatory, and antiamyloidogenic effects in the cortex, striatum, hippocampus, and cerebellum. Methods: Male Wistar rats were divided into four experimental groups: control (icv normal saline solution), STZ (icv STZ-3 mg/kg), STZ + iTBS (STZ rats subjected to iTBS protocol), and STZ + Placebo (STZ animals subjected to placebo iTBS noise artifact). Biochemical assays and immunofluorescence microscopy were used to evaluate functional and structural changes. Results: The icv STZ administration induces oxidative stress and attenuates antioxidative capacity in all examined brain regions. iTBS treatment significantly reduced oxidative and nitrosative stress parameters. Also, iTBS decreased Aβ-1-42 and APP levels. The iTBS enhances antioxidative capacity reported as elevated activity of its enzymatic and non-enzymatic components. In addition, iTBS elevated BDNF expression and attenuated STZ-induced astrogliosis confirmed by decreased GFAP + /VIM + /C3 + cell reactivity in the hippocampus. Discussion: Our results provide experimental evidence for the beneficial effects of the applied iTBS protocol in attenuating oxidative stress, increasing antioxidant capacity and decreasing reactive astrogliosis in STZ-administrated rats.
Archives of Biological Sciences, 2022
Colorectal cancer (CRC) is one of the most frequent forms of malignant tumors in the human popula... more Colorectal cancer (CRC) is one of the most frequent forms of malignant tumors in the human population. The literature data about the role of arginine metabolism in CRC point out its double-faced role. In three tissue specimens of 50 patients who underwent surgical resection for colon adenocarcinoma (tumor, adjacent and healthy tissues more than 10 cm from the tumor border-at the incision margin) taken during surgery, polyamines and the concentration of NO 2 +NO 3 and arginase activity were determined. Polyamine levels and arginase activity were significantly increased in cancer and adjacent tissue specimens compared to healthy ones, while the level of NO 2 +NO 3 was significantly lower in cancer compared to both adjacent and healthy tissues. The high polyamine content in the adjacent colonic mucosa indicates a high proliferative potential of tumor-adjacent tissue. Although we found individual correlations indicating the possible prognostic value of arginase, the performed statistical analysis did not show a predictive significance of arginase activity in the examined tissue specimens for five-year survival of the patients. Nevertheless, the obtained results provide the rationale for further studies of arginine metabolism in tissue specimens after surgery in patients with CRC, which could be useful in the evaluation of the risk for tumor growth, recurrence, metastases and survival after surgical intervention.
Acta Medica Medianae, Jan 15, 2016
Colorectal cancer is one of the most frequent human malignant diseases and one of the most common... more Colorectal cancer is one of the most frequent human malignant diseases and one of the most common causes of malignant diseases death. Oxidative and nitrosative stress have an important role in cancer initiation and propagation. That is why this study is focused on the determination of oxidative and nitrosative stress markers in tumor, adjacent and health tissue, which are important for the estimation of tumor proliferative and angiogenic potential. The study encompassed 50 patients who underwent surgery due to colorectal cancer. In the tissue samples from resected colon preparation (tumor, adjacent and healthy tissue, at least 10 cm distant from tumor), oxidative and nitrosative stress markers, malondialdehyde (MDA) and nitric oxide (NO) were determined. The obtained results prove the presence of oxidative stress in tumor tissue. Highly significantly (p<0.001) increased MDA concentrations in both tumor and adjacent tissue (12.43±9.39 and 11.57±5.56 nmol/mg proteins) compared to healthy one (7.25±5.52) reflect higher tumor aggressiveness and metastatic capacity. Higher NO concentrations in adjacent tissue (85.100±37.972 nmol/mg prot.) compared to the tumor one (58.608±22.789) point out high angiogenic potential of tumor surrounding tissue, which could have the clinical importance in the assessment of tumor invasiveness and the probability of local recurrence. In conclusion, the determination of the intensity of reactive oxygen and nitrogen species generation in tumor and adjacent colon tissue of patients with colorectal carcinoma could be useful in the estimation of the cancer invasive and metastatic capacity related to the prognosis of the disease and the choice of adjuvant therapy.
Journal of the Neurological Sciences, Oct 1, 2013
(AQP) 4 antibodies were examined using a cell-based assay. Results: Five patients developed MS (1... more (AQP) 4 antibodies were examined using a cell-based assay. Results: Five patients developed MS (14.7%); of these, 2 revealed relapses of the different lesions and 3 revealed other lesions on brain MRI. Moreover 21 were classified as still having CIS (61.8%). The remaining 8 patients had a neuromyelitis optica-related disorder (NMOrd); 3 patients demonstrated anti-AQP4 antibodies, and 5 revealed a centrally located long spinal cord lesion on MRI (1 patient demonstrated both lesions). OCBs were observed in CSF at the first visit in 2 of 5 (40%), 3 of 21 (14.3%), and 3 of 8 (37.5%) patients who revealed conversion to MS, nonconversion, and NMOrd, respectively. Conclusion: Two of 5 patients with CIS and OCBs developed MS for only for 38 months; moreover, NMOrd was observed in 8 of 34 with CIS (23.5%). This study suggests that CSF-OCBs could be helpful in predicting MS development in Japanese patients with a low incidence of OCB (47.6% of different our series) and that Japanese patients with CIS have a low risk of MS development.
Jikken Dobutsu, 2017
Chlorpromazine (CPZ) is a member of a widely used class of antipsychotic agents. The metabolic pa... more Chlorpromazine (CPZ) is a member of a widely used class of antipsychotic agents. The metabolic pathways of CPZ toxicity were examined by monitoring oxidative/nitrosative stress markers. The aim of the study was to investigate the hypothesis that agmatine (AGM) prevents oxidative stress in the liver of Wistar rats 48 h after administration of CPZ. All tested compounds were administered intraperitoneally (i.p.) in one single dose. The animals were divided into control (C, 0.9% saline solution), CPZ (CPZ, 38.7 mg/kg b.w.), CPZ+AGM (AGM, 75 mg/kg b.w. immediately after CPZ, 38.7 mg/kg b.w. i.p.), and AGM (AGM, 75 mg/kg b.w.) groups. Rats were sacrificed by decapitation 48 h after treatment. The CPZ and CPZ+AGM treatments significantly increased thiobarbituric acid reactive substances (TBARS), the nitrite and nitrate (NO 2 +NO 3) concentration, and superoxide anion (O 2 •-) production in rat liver homogenates compared with C values. CPZ injection decreased the capacity of the antioxidant defense system: superoxide dismutase (SOD) activity, catalase (CAT) activity, total glutathione (GSH) content, glutathione peroxidase (GPx) activity, and glutathione reductase (GR) activity compared with the values of the C group. However, treatment with AGM increased antioxidant capacity in the rat liver; it increased the CAT activity, GSH concentration, GPx activity, and GR activity compared with the values of the CPZ rats. Immunohistochemical staining of ED1 in rats showed an increase in the number of positive cells 48 h after acute CPZ administration compared with the C group. Our results showed that AGM has no protective effects on parameters of oxidative and/or nitrosative stress in the liver but that it absolutely protective effects on the antioxidant defense system and restores the antioxidant capacity in liver tissue after administration of CPZ.
Behavioural Brain Research
Folia biologica, 2017
Oxidative stress plays important roles in the pathophysiology of acute myocardial infarction (AMI... more Oxidative stress plays important roles in the pathophysiology of acute myocardial infarction (AMI). The aim of this study was to investigate the correlation of the oxidative stress status and matrix metalloproteinase activity in AMI patients in comparison to controls. This study included 136 subjects: 68 patients with AMI (42 males/26 females; mean age 58.5 ± 10.5 years) and 68 controls (37 males/29 females; mean age 60.2 ± 12.4 years). Gelatinases A and B were assayed using gelatin zymography, enzyme activities were obtained spectrophotometrically. Gelatinase A and B activities were increased in the AMI patients' group compared to the control. Activities of serum superoxide dismutase (SOD) and xanthine oxidase (XO) were significantly higher in AMI patients (106.53 ± 23.45 U/l, P < 0.001 and 158.18 ± 29.59 U/l, P < 0.001) than in the control group (55.99 ± 10.79 U/l and 79.81 ± 7.93 U/l). The activity of catalase (CAT) in the sera of AMI patients was lower (271.31 ± 7.53 U...
Vojnosanitetski pregled, 2021
Background/Aim. Experimental autoimmune encephalomyelitis (EAE) is a model of multiple sclerosis ... more Background/Aim. Experimental autoimmune encephalomyelitis (EAE) is a model of multiple sclerosis (MS), in which we investigated the neuroprotective effect of agmatine (AGM), known as a primary amine produced via the decarboxylation of L-arginine. Methods. Dark Agouti rats were divided into groups: control (C), Complete Freund`s Adjuvant (CFA), EAE rats decapitated on the 13th day post immunization (dpi) (EAE13) and on the 20th dpi (EAE20), EAE animals given three (EAE+AGM13) and 10 (EAE+AGM20) doses of AGM, and healthy animals ad-ministered three/10 doses of AGM (AGM). Thiobarbituric acid-reacting substances (TBARS), SH groups (SH), total glutathione (GSH), glutathione peroxidase activity (GPx), superoxide dismutase activities (tSOD, MnSOD, CuZ-nSOD) and nitrite/nitrate concentration (NO2+NO3) were assessed in plasma and brain structures [whole encephalitic mass (WEM) and brainstem (BS)]. Results. The obtained results showed that AGM treatment successfully attenuated severe clinical...
Acta Veterinaria Brno, 2018
This study was aimed to study the potentially beneficial effects of agmatine on oxidative/nitrosa... more This study was aimed to study the potentially beneficial effects of agmatine on oxidative/nitrosative stress development in the brain of Wistar rats during subacute chlorpromazine treatment. The animals were divided into control (0.9% saline), chlorpromazine (38.7 mg/kg b.w.), chlorpromazine+agmatine (agmatine 75 mg/kg b.w. immediately after chlorpromazine, 38.7 mg/kg b.w. i.p.) and agmatine (75 mg/kg b.w.) groups. All the tested substances were administered intraperitoneally for 15 consecutive days and the rats were sacrificed by decapitation on day 15. Subacute administration of chlorpromazine resulted in increased lipid peroxidation, nitric oxide concentration and superoxide anion production, while completely damaging the antioxidant defence system in the cerebral cortex, striatum, and hippocampus. However, the combined treatment with chlorpromazine and agmatine significantly attenuated the oxidative/nitrosative stress indices and restored the antioxidant capacity to the control ...
Pteridines, 2017
Clinical practice and experimental studies have shown the necessity of sufficient quantities of f... more Clinical practice and experimental studies have shown the necessity of sufficient quantities of folic acid intake for normal embryogenesis and fetal development in the prevention of neural tube defects (NTDs) and neurological malformations. So, women of childbearing age must be sure to have an adequate folate intake periconceptionally, prior to and during pregnancy. Folic acid fortification of all enriched cereal grain product flour has been implemented in many countries. Thus, hundreds of thousands of people have been exposed to an increased intake of folic acid. Folate plays an essential role in the biosynthesis of methionine. Methionine is the principal aminopropyl donor required for polyamine biosynthesis, which is up-regulated in actively growing cells, including cancer cells. Folates are important in RNA and DNA synthesis, DNA stability and integrity. Clinical and epidemiological evidence links folate deficiency to DNA damage and cancer. On the other hand, long-term folate ove...
Vojnosanitetski pregled, 2017
Background/Aim. Nowadays therapy with fixed orthodontic appliances is widely spread, having in mi... more Background/Aim. Nowadays therapy with fixed orthodontic appliances is widely spread, having in mind positive effects it has in malocclusion treatments The side effect is increased gingivial inflammation in treated patients. The aims of this research are to estimate the inflammatory condition of gingiva in the first 6 months of orthodontic therapy on the basis of clinical parameters of sulcus bleeding index, plaque index, gingival crevicular fluid and salivary nitric oxide concentration, and to investigate role of nitric oxide as predicting factor of gingival inflammation in orthodontic patients. Methods. In this study, 30 patients of the Dental Clinic treated with fixed orthodontic appliances (11 males and 19 females), aged 15-22 years, were examined. Clinical parameters were evaluated and gingival crevicular fluid and saliva were collected, before the beginning of orthodontics therapy, and then, three and six months after it. Results. The approximate values of clinical parameters, ...
Neurochemistry International, 2016
Repetitive transcranial magnetic stimulation (rTMS) induces changes in expression of proteins eng... more Repetitive transcranial magnetic stimulation (rTMS) induces changes in expression of proteins engaged in activity of excitatory and inhibitory systems as well as redox homeostasis. Our aim was to investigate the effect of single (SS) and repeated session (RS) of intermittent and continuous theta-burst stimulation (iTBS; cTBS) on the expression of vesicular and plasmatic glutamate transporters 1 (vGluT1 and GLT-1), glial fibrillary acidic protein (GFAP) and influence on oxidative status in rats cerebellar tissue and plasma. Redox state parameters in cerebellar tissue and plasma were assessed 24 h after single and 48 h after the last TBS session. Molecular changes were examined by immunofluorescence. Stimulation significantly increased thiol groups (SH) in tissue of SS iTBS group, and decreased in iTBS RS. Activity of glucose-6-phosphate-dehydrogenase (G6PD) was increased markedly in cTBS RS. Immunoreactivity of vGluT1 in cTBS RS decreased, while GLT-1 increased in cTBS SS and cTBS RS, compared to control. Present study gives insight in molecular and biochemical mechanisms by which iTBS and cTBS exerts its effects on rats cerebellar cortex.
Acta Facultatis Medicae Naissensis, 2016
SummaryThe metabolic pathways of chlorpromazine (CPZ) toxicity were tracked by assessing oxidativ... more SummaryThe metabolic pathways of chlorpromazine (CPZ) toxicity were tracked by assessing oxidative/nitrosative stress markers. The main objective of the study was to test the hypothesis that agmatine (AGM) prevents oxidative/nitrosative stress in the liver of Wistar rats 15 days after administration of CPZ. All tested substances were administered intraperitoneally (i.p.) for 15 consecutive days. The rats were divided into four groups: the control group (C, 0.9 % saline solution), the CPZ group (CPZ, 38.7 mg/kg b.w.), the CPZ+AGM group (AGM, 75 mg/kg b.w. immediately after CPZ, 38.7 mg/kg b.w. i.p.) and the AGM group (AGM, 75 mg/kg b.w.).Rats were decapitated 15 days after the appropriate treatment. In the CPZ group, CPZ concentration was significantly increased compared to C values (p<0.01), while AGM treatment induced the significant decrease in CPZ concentration in the CPZ+AGM group (p<0.05) and the AGM group (p<0.01). CPZ application to healthy rats did not lead to any c...
Neurochemical Research, 2015
The aim of the study is to investigate the hypothesis that agmatine (AGM) enhances blood brain ba... more The aim of the study is to investigate the hypothesis that agmatine (AGM) enhances blood brain barrier (BBB) compounds properties in experimental autoimmune encephalomyelitis (EAE), which is an established animal model for studying multiple sclerosis (MS). Wild-type (WT) and knockout (KO) CBA/H iNOS-/- mice, 3 months old (15 ± 5 g) were used for EAE induction by myelin basic protein (MBP) dissolved in complete Freund&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s adjuvant (CFA). The animals were divided into control, CFA, EAE, EAE + AGM and AGM groups. After the development of full clinical remission, the animals were sacrificed and the immunohistochemical and biochemical examinations were performed in brain homogenates. We had noticed the increased expressions of occludin in WT and KO mice with EAE + AGM, compared to EAE groups in which these expressions were significantly decreased compared to the controls. The significant elevations of matrix metalloproteinases (MMPs)-MMP-3 and MMP-9 in WT and KO EAE animals were decreased during AGM treatment in both groups. AGM application post EAE in WT and KO mice caused decreased level of Iba-1 stain, compared to EAE groups. The obtained results suggest beneficial AGM effects in EAE on BBB components, which might be useful for novel therapeutic strategies in MS.
Journal of the Neurological Sciences, 2013
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Papers by Ivana Stojanovic