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Gentiopicroside (Gp) and swertiamarin (Sm), secoiridoid glycosides commonly found in plants of the Gentianaceae family, differ in one functional group. They exhibit promising cytotoxic effects in cancer cell lines and overall protective outcomes, marking them as promising molecules for developing novel pharmaceuticals. To investigate potential variations in cellular sensitivity to compounds of similar molecular structures, we analyzed the mode of Gp and Sm induced cell death in human peripheral blood mononuclear cells (PBMCs) after 48 h of treatment. The lowest tested concentration that significantly reduces cell viability, 50 μM, was applied. Oxidative stress parameters were estimated by measuring the levels of prooxidative/antioxidative balance, lipid peroxidation products, and 8-oxo-7,8-dihydro-2-deoxyguanosine, while gene expression of DNA repair enzymes was evaluated by employing quantitative real-time PCR. Cellular morphology was analyzed by fluorescent microscopy, and immunoblot analysis of apoptosis and necroptosis-related proteins was used to assess the type of cell death induced by the treatments. The discriminatory impact of Gp/Sm treatments on apoptosis and necroptosis-induced cell death was evaluated by monitoring the cell survival in co-treatment with specific cell death inhibitors. Obtained results show greater cytotoxicity of Gp than Sm suggesting that variations in the molecular structures of the tested compounds can substantially affect their biological effects. Gp/Sm co-treatment with apoptosis and necroptosis inhibitors revealed a distinct, albeit non-specific mechanism of PBMCs cell death. Although the therapeutic may not directly cause a specific type of cell death, its extent can be pivotal in assessing the safety of therapeutic application and developing phytopharmaceuticals with improved features. Since phytopharmaceuticals affect all exposed cells, identification of cytotoxic mechanisms on PBMCs after Gp and Sm treatment is important for addressing the formulation and dosage of potential phytopharmaceuticals., Competing Interests: Declaration of Competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chronic exposure to stress alters the prooxidant-antioxidant balance, which might lead to the development of various human pathological states. In order to explain the role of antioxidant response in stress-induced injury, we examined the effects of two types of acute stress, as well as combined effects of chronic and acute stress on manganese-superoxide dismutase, copper,zinc-superoxide dismutase, and catalase activities in rat brain hippocampus. Our results show that chronic stress induces an increase in oxidative enzyme activities and that adaptation to chronic stress might alter hippocampal antioxidant mechanisms' response to acute stress.

While the effects of chronic exposure to microplastic particles (MPs) are extensively studied, the outcomes of a single treatment have received relatively less attention. To investigate MPs' potential acute toxicity, including their impact on general health status (victual consumption, sensorimotor deficits, and clinical toxicity signs) and serum biochemical parameters (markers of organ/tissue function and oxidative stress indicators), we administered thoroughly characterized MPs (1.4, 35, or 125 mg/kg), generated from polyethylene terephthalate (PET) bottles, to adult male Wistar rats via oral gavage. The MPs' short-term effects were assessed with well-established tests and methods. The results point to the absence of sensorimotor deficits and clinical toxicity signs, while levels of markers of liver, heart, and kidney function were altered in all MP groups. Decreased victual consumption and increased levels of oxidative stress indicators were evident following treatment with the two higher MP doses. Presented data indicate that examined MPs are able to initiate the development of local changes in tissues and organs within a short time frame, potentially leading to their damage and dysfunction. This study may increase the awareness of the detrimental effects of plastic contamination, as even a single exposure to MPs may provoke adverse health outcomes. [ABSTRACT FROM AUTHOR]

The radioactive iodine (131I) ablation is a well-accepted treatment modality for differentiated thyroid cancer patients. Unfortunately, the radiation induces the oxidative stress and damages cells and tissues, simultaneously activating the mechanisms of antioxidative defense. Since the mechanisms of those processes are not completely known, we wanted to examine the changes in the most important reactive oxygen species and antioxidative components, as well as their correlation and significance for lipid peroxidation. Our results showed that the level of thiobarbituric acid reactive substances was increased during the first 30 days after the radiotherapy. Among antioxidant components, superoxide dismutase was increased in the 3rd and 30th day; catalase in 7th and reduced glutathione in 3rd and 7th day after the radiotherapy. As regards the prooxidants, the reduction of hydrogen peroxide (H2O2) was recorded in 7th and 30th day, and superoxide anion radical (O×-) was unchanged after the exposure to 131I. These results indicate that differentiated thyroid cancer patients are under constant oxidative stress despite the observed increase in antioxidative and reduction in prooxidative parameters. The understanding of these early processes is important since their progress determines the latter effects of 131I therapy. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III41007 and Grant no. 175007]

Nanoparticles (NPs), a distinct class of particles ranging in size from 1 to 100 nm, are one of the most promising technologies of the 21st century, and titanium dioxide NPs (TiO2 NPs) are among the most widely produced and used NPs globally. The increased application of TiO2 NPs raises concerns regarding their global safety and risks of exposure. Many animal studies have reported the accumulation of TiO2 NPs in female reproductive organs; however, evidence of the resultant toxicity remains ambiguous. Since the surface area and chemical modifications of NPs can significantly change their cytotoxicity, we aimed to compare the toxic effects of pristine TiO2 powder with surface-modified TiO2 powders with salicylic acid (TiO2/SA) and 5-aminosalicylic acid (TiO2/5-ASA) on the ovaries, oviducts, and uterus on the 14th day following acute oral treatment. The results, based on alterations in food and water intake, body mass, organ-to-body mass ratio, hormonal status, histological features of tissues of interest, and antioxidant parameters, suggest that the modification with 5-ASA can mitigate some of the observed toxic effects of TiO2 powder and encourage future investigations to create NPs that can potentially reduce the harmful effects of TiO2 NPs while preserving their positive impacts. [ABSTRACT FROM AUTHOR]

Introduction: The oxidative stress contributes to all three phases of carcinogenesis and represents a concomitant condition in renal cell carcinoma (RCC). RCC is the most common type of neoplasm of the kidney, and despite numerous studies the set of predictive and prognostic markers of survival are still unknown. The aim of our study was to examine the relation between antioxidant (AO) status and overall survival (OS) in RCC patients.Material and Methods: Our study included 95 patients with RCC, who underwent radical nephrectomy. We analysed the prognostic role of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase, glutathione, and malondialdehyde) and other clinicopathological factors (size, grade, stage, and histological subtype) on the OS of RCC patients.Results: The 5-year OS was 54.6%. The survival analysis related to AO parameters showed no significant difference in survival of RCC patients. The concentration of malondialdehyde, an indicator of lipid peroxidation, also had no significant effect on the survival rate of RCC patients. Univariate and multivariate analysis confirmed the significance of clinicopathological parameters (size, p < 0.001; Fuhrman grade, p = 0.001, and stage, p < 0.001) for patients' survival.Conclusions: In our cohort of patients, different antioxidant parameters were not found to be predictors for OS of patients with RCC, who underwent radical nephrectomy. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To explain the role of oxidative stress in the pathology of celiac disease. Design and methods: The activities of antioxidant enzymes and the levels of glutathione and lipid hydroperoxides were measured in the samples of small intestinal biopsies from 39 children with different forms of the disease and in 19 control subjects. Results: The activities of analyzed enzymes varied significantly between the examined groups. An increase in the activities of superoxide dismutase was observed in patients with active and silent celiac disease, while the activities of glutathione peroxidase and glutathione reductase and the glutathione content were significantly reduced. The level of lipid hydroperoxides was significantly elevated in these groups. Conclusions: Oxidative stress is an important factor in the pathogenesis of celiac disease. The antioxidant capacity of celiac patients is significantly reduced, mostly by a depletion of glutathione. Natural antioxidants and appropriate dietary supplements could be important complements to the classic therapy of celiac disease. [Copyright &y& Elsevier]

Background: Oxidative stress has been implicated in the pathogenesis of coeliac disease. The aim of this study was to examine the modulation of the biochemical response to oxidative stress in untreated and treated coeliac disease. Methods: The study involved peripheral blood samples from 39 paediatric patients (18 with active, 11 with silent form of the disease, 10 on gluten-free diet [GFD]) and 30 control subjects. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the concentrations of total glutathione (GSH) and lipid hydroperoxides (LOOH) were determined in patients and controls. Results: In comparison to the controls, a significant increase in SOD activity was found in the active group (P<0.05), while CAT activity was elevated in GFD group (P<0.05). GPx activity was lower in patients than in controls (active and silent, P<0.001; GFD, P<0.01). GSH contents were significantly reduced in all patient groups (P<0.001) as well, while the concentration of LOOH was elevated in active and silent group (P<0.001). The concentration of LOOH correlated negatively with the activity of GPx (r = -0.32, P<0.01) and the concentration of GSH (r = -0.70, P<0.001). A significant positive correlation was found between the concentration of GSH and the activity of GPx (r = 0.57, P<0.001). Conclusions: The results show evidence of increased oxidative stress in untreated coeliac disease. Although LOOH were not significantly elevated in the GFD group, changes in antioxidant enzyme activities and GSH content demonstrate that oxidative stress persists even in treated patients. [ABSTRACT FROM AUTHOR]

A dysregulated and overwhelming response to an infection accompanied by the exaggerated pro-inflammatory state and metabolism disturbance leads to the fatal outcome in sepsis. Previously we showed that meldonium, an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, strongly increases mortality in faecal-induced peritonitis (FIP) in rats. We postulated that the same mechanism that is responsible for the otherwise strong anti-inflammatory effects of meldonium could be the culprit of the increased mortality. In the present study, we applied the LPS-induced model of sepsis to explore the presence of any differences from and/or similarities to the FIP model. When it comes to energy production, despite some shared similarities, it is evident that LPS and FIP models of sepsis differ greatly. A different profile of sympathoadrenal activation may account for this observation, as it was lacking in the FIP model, whereas in the LPS model it was strong enough to overcome the effects of meldonium. Therefore, choosing the appropriate model of sepsis induction is of great importance, especially if energy homeostasis is the main focus of the study. Even when differences in the experimental design of the two models are acknowledged, the role of different patterns of energy production cannot be excluded. On that account, our results draw attention to the importance of uninterrupted energy production in sepsis but also call for much-needed revisions of the current recommendations for its treatment. [ABSTRACT FROM AUTHOR]

Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical's scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role. [ABSTRACT FROM AUTHOR]