1. Disturbed antioxidant capacity in patients with systemic sclerosis associates with lung and gastrointestinal symptomsNeža Brezovec, Katja Perdan-Pirkmajer, Blaž Burja, Žiga Rotar, Joško Osredkar, Snežna Sodin-Šemrl, Katja Lakota, Saša Čučnik, 2023, izvirni znanstveni članek Povzetek: The correct balance between reactive oxygen species and antioxidant defense in an organism is disturbed in oxidative stress. To assess oxidative balance in 36 SSc patients and 26 healthy controls (HCs), we measured reactive oxidative metabolites (ROMs), total antioxidant capacity (TAC), lipid peroxidation (measuring 4-HNE), and DNA oxidative damage (measuring 8-OHdG) in serum. Furthermore, DNA breaks in leukocytes of 35 SSc patients and 32 HCs were evaluated using COMET. While we report high ROMs for both SSc patients and age/sex matched HC samples, there was a significant increase in TAC in SSc patients as compared to HCs, and thus also a significantly higher oxidative stress index in SSc patients. TAC was significantly higher in SSc patients with ILD and gastrointestinal involvement, as well as in patients with anti-topoisomerase antibodies. We observe no difference in serum lipid peroxidation status or oxidative DNA damage. However, SSc patients had significantly more leukocyte DNA breaks than HCs; the most damage was observed in patients treated with immunosuppressives. Thus, our study confirms presence of oxidative stress and increased DNA damage in leukocytes of SSc patients; however, it points toward increased antioxidant capacity, which needs to be further studied. Ključne besede: systemic sclerosis, oxidative stress, reactive oxidative metabolites, antioxidants, lipid peroxidation, DNA damage, DNA breaks Objavljeno v DiRROS: 05.08.2026; Ogledov: 182; Prenosov: 73
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2. Genetic polymorphisms in oxidative stress and inflammatory pathways as potential biomarkers in Alzheimer’s Disease and dementiaDavid Vogrinc, Milica Gregorič Kramberger, Andreja Emeršič, Saša Čučnik, Katja Goričar, Vita Dolžan, 2023, izvirni znanstveni članek Povzetek: Oxidative stress and neuroinflammation are important processes involved in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Numerous risk factors, including genetic background, can affect the complex interplay between those mechanisms in the aging brain and can also affect typical AD hallmarks: amyloid plaques and neurofibrillary tangles. Our aim was to evaluate the association of polymorphisms in oxidative stress- and inflammation-related genes with cerebrospinal fluid (CSF) biomarker levels and cognitive test results. The study included 54 AD patients, 14 MCI patients with pathological CSF biomarker levels, 20 MCI patients with normal CSF biomarker levels and 62 controls. Carriers of two polymorphic IL1B rs16944 alleles had higher CSF Aβ1–42 levels (p = 0.025), while carriers of at least one polymorphic NFE2L2 rs35652124 allele had lower CSF Aβ1–42 levels (p = 0.040). Association with IL1B rs16944 remained significant in the AD group (p = 0.029). Additionally, MIR146A rs2910164 was associated with Aβ42/40 ratio (p = 0.043) in AD. Significant associations with cognitive test scores were observed for CAT rs1001179 (p = 0.022), GSTP1 rs1138272 (p = 0.005), KEAP1 rs1048290 and rs9676881 (both p = 0.019), as well as NFE2L2 rs35652124 (p = 0.030). In the AD group, IL1B rs1071676 (p = 0.004), KEAP1 rs1048290 and rs9676881 (both p = 0.035) remained associated with cognitive scores. Polymorphisms in antioxidative and inflammation genes might be associated with CSF biomarkers and cognitive test scores and could serve as additional biomarkers contributing to early diagnosis of dementia. Ključne besede: Alzheimer’s disease, oxidative stress, inflammation Objavljeno v DiRROS: 03.08.2026; Ogledov: 187; Prenosov: 72
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3. Toxicity assessment of three emerging bisphenols (BPA, BPAP and BPC) and their binary mixtures in an advanced in vitro 3D HepG2 cell modelMartina Štampar, Tim Ravnjak, Alja Štern, Bojana Žegura, 2026, izvirni znanstveni članek Povzetek: Bisphenols (BPs) are industrial chemicals extensively used in polycarbonate plastics and epoxy resins for everyday products, including food and beverage containers, toys, and thermal paper, representing major sources of human exposure. Bisphenol A (BPA) is the most prevalent; however, due to its endocrine-disrupting, reproductive, and genotoxic effects, it is classified as a substance of high concern by the European Chemicals Agency. Regulatory restrictions have prompted the use of structural analogues, including bisphenol AP (BPAP) and bisphenol C (BPC); however, emerging evidence suggests they may pose similar or greater health risks. Comprehensive data on their toxicity and human exposure, especially in mixtures, remain limited. This study assessed the cytotoxic and genotoxic effects of BPA, and less studied analogues BPAP, BPC, and their binary mixtures using a human-relevant 3D HepG2 spheroid model, representing an advanced in vitro system. Spheroids were exposed for 24 and 96 h, and effects were evaluated by ATP-based viability assays, comet assay, and targeted transcriptomics. None of the bisphenols induced significant cytotoxicity, although slight reductions in viability were observed for BPAP, BPC, and mixtures. DNA strand breaks were detected after exposure to BPA, BPC, and mixtures. Transcriptomic analysis revealed modest stress responses and strong upregulation of xenobiotic metabolism genes (CYP1A1, CYP1A2, CYP3A4, UGT1A1, NAT2), indicating cellular recognition of the tested bisphenols as bioactive xenobiotics. Antioxidant and DNA repair genes were largely unchanged, except for upregulation of oxidative stress markers HMOX1 and SRXN1 and a slight increase in OGG1, indicating oxidative DNA damage. Importantly, mixture effects were predominantly additive, with no evidence of synergistic interactions under the tested conditions. Overall, bisphenol exposure primarily triggered oxidative stress and metabolic responses rather than robust DNA damage signalling, suggesting that genotoxicity is largely mediated by reactive oxygen species. By integrating multiple endpoints in a 3D liver model, this study provides a more comprehensive assessment of bisphenol toxicity and highlights potential risks associated with BPA analogues and their mixtures, supporting the need for a comprehensive safety assessment to evaluate their suitability as replacements in consumer products. Ključne besede: bisphenol, DNA damage, oxidative stress, complex mixtures, metabolism Objavljeno v DiRROS: 10.07.2026; Ogledov: 178; Prenosov: 187
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4. Oxidative stress-related biomarkers as promising indicators of inflammatory bowel disease activity : a systematic review and meta-analysisArmando Tratenšek, Igor Locatelli, Iztok Grabnar, David Drobne, Tomaž Vovk, 2024, izvirni znanstveni članek Povzetek: Oxidative stress is believed to play an important role in the pathogenesis of inflammatory bowel disease (IBD), specifically Crohn's disease (CD) and ulcerative colitis (UC). This meta-analysis aimed to identify and quantify the oxidative stress-related biomarkers in IBD and their associations with disease activity. We systematically searched Ovid MEDLINE, Ovid Embase, and Web of Science databases, identifying 54 studies for inclusion. Comparisons included: (I) active IBD versus healthy controls; (II) inactive IBD versus healthy controls; (III) active CD versus inactive CD; and (IV) active UC versus inactive UC. Our analysis revealed a significant accumulation of biomarkers of oxidative damage to biomacromolecules, coupled with reductions in various antioxidants, in both patients with active and inactive IBD compared to healthy controls. Additionally, we identified biomarkers that differentiate between active and inactive CD, including malondialdehyde, Paraoxonase 1, catalase, albumin, transferrin, and total antioxidant capacity. Similarly, levels of Paraoxonase 1, erythrocyte glutathione peroxidase, catalase, albumin, transferrin, and free thiols differed between active and inactive UC. Vitamins and carotenoids likewise emerged as potential disease activity biomarkers for CD and UC, but their intake should be monitored to obtain meaningful results. These findings emphasize the involvement of oxidative stress in the pathogenesis of IBD and highlight the potential of oxidative stress-related biomarkers as a minimally invasive and additional tool for monitoring the activity of IBD. Ključne besede: inflammatory bowel disease, ulcerative colitis, Crohn's disease, oxidative stress, biomarker, meta-analysis Objavljeno v DiRROS: 01.07.2026; Ogledov: 214; Prenosov: 179
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5. Effectiveness of oral glutathione in reducing nitric oxide and IL-1α concentrations for clinical improvement in mild to moderate acne vulgaris : a randomized controlled trialFerra Olivia Mawu, Anis Irawan Anwar, Khairuddin Djawad, Agussalim Bukhari, Marlyn Grace Kapantow, Paulus Mario Christopher, 2025, izvirni znanstveni članek Povzetek: Introduction: Acne vulgaris (AV) is a chronic inflammatory dermatosis predominantly affecting adolescents and young adults. Oxidative and nitrosative stress, marked by elevated nitric oxide (NO) and interleukin (IL)-1α, contributes to AV pathogenesis. Glutathione, a key antioxidant, may attenuate oxidative and nitrosative stress and modulate inflammatory pathways. This study investigates the effectiveness of oral glutathione supplementation on serum NO and IL-1α concentrations, and clinical improvement in mild to moderate AV patients. Methods: A randomized controlled trial was conducted involving 40 subjects diagnosed with mild to moderate AV. Participants were randomized to receive either 500 mg oral glutathione (n = 22) or placebo (n = 18) once daily for 4 weeks. Clinical severity of AV was assessed utilizing the Lehmann criteria. Serum levels of NO and IL-1α were measured at baseline and week 4. Results: At week 4, reductions in serum NO and IL-1α concentrations were observed in the glutathione group; however, these changes did not reach statistical significance (p > 0.05). Clinical improvement occurred in seven subjects (31.8%) in the glutathione group, with a reduction from moderate to mild severity. No adverse reactions were reported. Conclusions: Oral glutathione supplementation demonstrated a non-significant trend toward reducing oxidative and nitrosative stress markers and improving mild to moderate AV. Further studies are recommended to validate these findings. Ključne besede: acne vulgaris, oxidative stress, nitric oxide, glutathione, interleukin-1α Objavljeno v DiRROS: 15.06.2026; Ogledov: 246; Prenosov: 197
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6. Methylprednisolone does not enhance paraoxonase 1 activity during cardiopulmonary bypass surgery : a randomized, controlled clinical trialGordana Taleska Štupica, Maja Šoštarič, Matej Jenko, Matej Podbregar, 2024, izvirni znanstveni članek Ključne besede: paraoxonase 1, cardiopulmonary bypass, oxidative stress, inflammation, glucocorticoids, methylprednisolone Objavljeno v DiRROS: 11.06.2026; Ogledov: 240; Prenosov: 247
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7. Effect of antioxidant-rich kindergarten meals on oxidative stress biomarkers in healthy 5-6-year-old children : a randomized controlled trialMaja Berlic, Mojca Korošec, Žiga Iztok Remec, Vanja Čuk, Tadej Battelino, Barbka Repič-Lampret, 2024, izvirni znanstveni članek Povzetek: As children spend up to 9 h a day in kindergarten, the main purpose of our study was to evaluate the effect of antioxidant-rich kindergarten meals on oxidative stress biomarkers (OSBs) in healthy children. In the randomized control trial with a follow-up, healthy 5–6-year-old children from six kindergartens were randomly divided into a prototype group (PG, n=40) and a control group (CG, n=17). PG followed a 2-week antioxidant-rich kindergarten meal plan (breakfast, lunch, and two snacks), and CG followed their standard kindergarten meal plans. Outside the kindergartens, participants ate as usual. We used a consecutive 7-day dietary record inside and outside the kindergarten and the national dietary assessment tool OPEN to assess the total dietary antioxidant capacity (dTAC) of the consumed foods. Malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and four F2-isoprostane were measured in fasting urine on days 1 and 15. We also measured total antioxidant power (PAT) and hydroperoxides (d-ROMs) in fasting serum on day 15 and obtained the value of the oxidative stress index (OSI). We used a Welch two-sample t-test and multiple regression analysis to compare the prototype and control groups and a nonparametric Wilcoxon signed rank exact test to compare pre- and post-intervention results in urine. Antioxidant-rich kindergarten meals contributed to a significantly (p<0.05) higher intake of dTAC in PG participants compared to standard meals in CG participants (8.6 vs. 2.8 mmol/day). We detected a negative correlation between dTAC intake and d-ROMs and between dTAC intake and OSI (r= −0.29, p=0.043 and r= −0.31, p=0.032, respectively). A significant decrease in urinary 8-iso-15-prostaglandin-F-2 alpha was detected in PG participants between days 1 and 15; however, no other intra-individual significant differences in urinary OSBs were found. Ključne besede: antioxidant-rich diet, oxidative stress biomarkers, dietary antioxidant capacity, reactive oxygen metabolites, F2-isoprostanes, kindergarten diet Objavljeno v DiRROS: 08.06.2026; Ogledov: 211; Prenosov: 163
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8. Genetic variability in oxidative stress, inflammatory, and neurodevelopmental pathways: impact on the susceptibility and course of spinal muscular atrophyMaruša Barbo, Blaž Koritnik, Lea Leonardis, Tanja Blagus, Vita Dolžan, Metka Ravnik-Glavač, 2024, izvirni znanstveni članek Povzetek: The spinal muscular atrophy (SMA) phenotype strongly correlates with the SMN2 gene copy number. However, the severity and progression of the disease vary widely even among affected individuals with identical copy numbers. This study aimed to investigate the impact of genetic variability in oxidative stress, inflammatory, and neurodevelopmental pathways on SMA susceptibility and clinical progression. Genotyping for 31 genetic variants across 20 genes was conducted in 54 SMA patients and 163 healthy controls. Our results revealed associations between specific polymorphisms and SMA susceptibility, disease type, age at symptom onset, and motor and respiratory function. Notably, the TNF rs1800629 and BDNF rs6265 polymorphisms demonstrated a protective effect against SMA susceptibility, whereas the IL6 rs1800795 was associated with an increased risk. The polymorphisms CARD8 rs2043211 and BDNF rs6265 were associated with SMA type, while SOD2 rs4880, CAT rs1001179, and MIR146A rs2910164 were associated with age at onset of symptoms after adjustment for clinical parameters. In addition, GPX1 rs1050450 and HMOX1 rs2071747 were associated with motor function scores and lung function scores, while MIR146A rs2910164, NOTCH rs367398 SNPs, and GSTM1 deletion were associated with motor and upper limb function scores, and BDNF rs6265 was associated with lung function scores after adjustment. These findings emphasize the potential of genetic variability in oxidative stress, inflammatory processes, and neurodevelopmental pathways to elucidate the complex course of SMA. Further exploration of these pathways offers a promising avenue for developing personalized therapeutic strategies for SMA patients. Ključne besede: inflammation, neurodegeneration, neurodevelopment, oxidative stress, single nucleotide polymorphism, spinal muscular atrophy Objavljeno v DiRROS: 04.06.2026; Ogledov: 223; Prenosov: 198
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9. Polyethylene microplastics as a vector of tributyltin in Mytilus galloprovincialis and their consequencesTanja Kobal, Tea Zuliani, Stoimir Kolarević, Margareta Kračun-Kolarević, Tatjana Simčič, Tatjana Mijošek Pavin, Andreja Ramšak, 2026, izvirni znanstveni članek Povzetek: Microplastic pollution is an increasing environmental issue in the marine environment due to its ubiquitous presence and its role as a vector for organic pollutants such as tributyltin (TBT). Adsorption of TBT onto microplastics (MP) can increase its availability to filter-feeding organisms by prolonging its retention time in the water column. We investigated whether polyethylene (PE) MP spheres (10–63 μm) could act as vectors for TBT transfer in the mussel Mytilus galloprovincialis by exposing it to PE MP (50 mg L− 1 ) and TBT (0.001 mg L− 1 ) separately and in co-exposure for 21 days. Efficient adsorption on PE MP was confirmed, and higher concentration of TBT was observed in the PE MP + TBT group compared to TBT only exposed group, indicating a vector effect. This led to higher toxicity in mussels, as the combined stress conditions in the PE MP + TBT group resulted in a significant decrease in the catalase activity after 14 days of the exposure. Higher ETS activity was observed in both exposed groups after seven days of exposure, followed by lower ETS activity at 14 and 21 days, indicating depletion of energy reserves. Pronounced responses in catalase and electron transport system (ETS) activity were observed in the hepatopancreas compared to the gill tissue. DNA damage was present in all exposed groups and increased over time. Ključne besede: mytilus galloprovincialis, tributyltin, PE microplastics, mitochondrial respiration, genotoxicity, oxidative stress Objavljeno v DiRROS: 18.05.2026; Ogledov: 276; Prenosov: 284
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10. Telomere length, oxidative stress, and kidney damage biomarkers in Fabry nephropathyTina Levstek, Erazem Bahčič, Bojan Vujkovac, Andreja Cokan Vujkovac, Tine Tesovnik, Žiga Iztok Remec, Vanja Čuk, Katarina Trebušak Podkrajšek, 2025, izvirni znanstveni članek Povzetek: Fabry nephropathy is a life-threatening complication of Fabry disease characterized by complex and incompletely understood pathophysiological processes possibly linked to premature aging. We aimed to investigate leukocyte telomere length (LTL), oxidative stress, and kidney damage biomarkers in relation to kidney function. The study included 35 Fabry patients and 35 age and sex-matched control subjects. Based on the estimated slope of the glomerular filtration rate, the patients were divided into two groups. Relative LTL was quantified by qPCR, urinary biomarkers 8-hydroxy-2′ -deoxyguanosine (8-OHdG) and malondialdehyde (MDA) by UHPLC-MS/MS, and kidney damage biomarkers by flow cytometry. There was no statistically significant difference in LTL between Fabry patients and controls. However, a significant difference was observed in male patients compared to their matched control subjects (p = 0.013). Oxidative stress biomarkers showed no differences between patients and controls, while significant differences were observed in urinary IGFBP7, EGF, and OPN levels between Fabry patients with stable kidney function and those with progressive nephropathy (FDR = 0.021, 0.002, and 0.013, respectively). Significant differences were also observed in plasma levels of cystatin C, TFF3, and uromodulin between patients with progressive nephropathy and controls (all FDR = 0.039). Along with these biomarkers (FDR = 0.007, 0.017, and 0.010, respectively), NGAL also exhibited a significant difference between the two patient groups (FDR = 0.017). This study indicates accelerated telomere attrition, which may be related to disease burden in males. Furthermore, analyses of urinary oxidative stress markers revealed no notable disparities between the different kidney function groups, indicating their limited utility. However, promising differences were found in some biomarkers of kidney damage in urine and plasma. Ključne besede: nephropathy, telomere length, oxidative stress, kidney damage, biomarker, aging Objavljeno v DiRROS: 10.04.2026; Ogledov: 357; Prenosov: 238
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