Comprehensive and critical view on the anti-inflammatory and immunomodulatory role of natural phenolic antioxidants.

The immune response encompasses innate and adaptive immunity, each with distinct and specific activities. The innate immune system is constituted by phagocytic cells, macrophages, monocytes and neutrophils, the cascade system, and different classes of receptors such as toll-like receptors that are exploited by the innate immune cells. The adaptive immune system is antigen-specific, encompassing memory lymphocytes and the corresponding specific receptors. Inflammation is understood as an activation of different signaling pathways such as toll-like receptors or nuclear factor kappa-light-chain-enhancer of activated B cells, with an increase in nitric oxide, inflammatory cytokines and chemokines. Increased oxidative stress has been identified as main source of chronic inflammation. Phenolic antioxidants modulate the activities of lymphocytes and macrophages by impacting cytokines and nitric oxide release, exerting anti-inflammatory effect. The nuclear-factor kappa-light-chain-enhancer of activated B cells signaling pathway and the mitogen-activated protein kinase pathway are targeted, alongside an increase in nuclear factor erythroid 2-related factor mediated antioxidant response, triggering the activity of antioxidant enzymes. The inhibitive potential on phospholipase A2, cyclooxygenase and lipoxygenase in the arachidonic acid pathway, and the subsequent reduction in prostaglandin and leukotriene generation, reveals the potential of phenolics as inflammation antagonists. The immunomodulative potential encompasses the capacity to interfere with proinflammatory cytokine synthesis and with the expression of the corresponding genes. A diet rich in antioxidants can result in prevention of inflammation-related pathologies. More investigations are necessary to establish the role of these antioxidants in therapy. The appropriate delivery system and the prooxidant effects exhibited at large doses, or in the presence of heavy metal cations should be regarded.

Interplay of Oxidative Stress, Inflammation, and Autophagy in RAW 264.7 Murine Macrophage Cell Line Challenged with Si/SiO2 Quantum Dots.

Quantum dots (QDs) with photostable fluorescence are recommended for imaging applications; however, their effect on living cells is incompletely understood. We aimed to elucidate the RAW 264.7 murine macrophage cell line's response to the Si/SiO2 QDs challenge. Cells were exposed to 5 and 15 µg/mL Si/SiO2 QDs for 6 h, 12 h, and 24 h. Cell metabolic activity and viability were assessed by MTT, live/dead, and dye-exclusion assays. Oxidative stress and membrane integrity were assessed by anion superoxide, malondialdehyde, and lactate dehydrogenase activity evaluations. Antioxidative enzyme activities were analyzed by kinetic spectrophotometric methods. Cytokines were analyzed with an antibody-based magnetic bead assay, PGE2 was assessed by ELISA, and Nrf-2, Bcl-2, Beclin 1, and the HSPs were analyzed by western blot. Autophagy levels were highlighted by fluorescence microscopy. The average IC50 dose for 6, 12, and 24 h was 16.1 ± 0.7 µg/mL. Although glutathione S-transferase and catalase were still upregulated after 24 h, superoxide dismutase was inhibited, which together allowed the gradual increase of malondialdehyde, anion superoxide, nitric oxide, and the loss of membrane integrity. G-CSF, IL-6, TNF-α, MIP-1ß, MCP-1, Nrf-2, PGE2, and RANTES levels, as well as autophagy processes, were increased at all time intervals, as opposed to caspase 1 activity, COX-2, HSP60, and HSP70, which were only upregulated at the 6-h exposure interval. These results underscore that Si/SiO2 QDs possess significant immunotoxic effects on the RAW 264.7 macrophage cell line and stress the importance of developing effective strategies to mitigate their adverse impact.

Predicting Pregnancy Outcome in Dairy Cows: The Role of IGF-1 and Progesterone.

The purpose of this study was to determine the link between insulin-like growth factor 1 (IGF-1), progesterone (PROG), non-esterified fatty acids (NEFAs), ß-hydroxybutyrate (BHB), and glucose (GLU) and pregnancy probability after the first artificial insemination (AI) and during the first 100 days in milk (DIM), during the critical transition period. We determined levels of serum IGF-1, PROG, NEFA, BHB, and GLU in Holstein dairy cows via ELISA, using blood samples collected 7 days before parturition (DAP) until 21 days postparturition (DPP). The group was split into cows diagnosed pregnant at 100 DIM (PREG) and those that did not conceive at 100 and 150 DIM (NPREG). Serum IGF-1 and PROG median levels at 7 DAP were significantly higher in PREG vs. NPREG (p = 0.029), the only statistically significant differences across the subgroups. At 7 DAP, IGF-1 levels within the initial group showed a strong negative correlation with PROG (r = -0.693; p = 0.006), while for the PREG subgroup, the IGF-1 levels exhibited a very strong positive correlation with GLU (r = 0.860; p = 0.011) and NEFA (r = 0.872; p = 0.013). IGF-1 and PROG levels detected at 7 DAP may be useful to predict pregnancy at 100 DIM. The positive correlation of NEFA and GLU levels during the transition period demonstrates that the initial group is not in NEB; thus, the NEFA level was not a decisive factor for reproduction success.

PCR Array Profiling of miRNA Expression Involved in the Differentiation of Amniotic Fluid Stem Cells toward Endothelial and Smooth Muscle Progenitor Cells.

Differentiation of amniotic fluid stem cells (AFSCs) into multiple lineages is controlled by epigenetic modifications, which include DNA methylation, modifications of histones, and the activity of small noncoding RNAs. The present study investigates the role of miRNAs in the differentiation of AFSCs and addresses how their unique signatures contribute to lineage-specific differentiation. The miRNA profile was assessed in AFSCs after 4 weeks of endothelial and muscular differentiation. Our results showed decreased expression of five miRNAs (miR-18a-5p, miR-125b-5p, miR-137, miR-21-5p, and let-7a) and increased expression of twelve miRNAs (miR-134-5p, miR-103a-3p, let-7i-5p, miR-214-3p, let-7c-5p, miR-129-5p, miR-210-3p, let-7d-5p, miR-375, miR-181-5p, miR-125a-5p, and hsa-let-7e-5p) in endothelial progenitor cells (EPCs) compared with undifferentiated AFSCs. AFSC differentiation into smooth muscle revealed notable changes in nine out of the 84 tested miRNAs. Among these, three miRNAs (miR-18a-5p, miR-137, and sa-miR-21-5p) were downregulated, while six miRNAs (miR-155-5p, miR-20a-5p, let-7i-5p, hsa-miR-134-5p, hsa-miR-214-3p, and hsa-miR-375) exhibited upregulation. Insights from miRNA networks promise future advancements in understanding and manipulating endothelial and muscle cell dynamics. This knowledge has the potential to drive innovation in areas like homeostasis, growth, differentiation, and vascular function, leading to breakthroughs in biomedical applications and therapies.

Mycotoxins and Essential Oils-From a Meat Industry Hazard to a Possible Solution: A Brief Review.

The preservation of food supplies has been humankind's priority since ancient times, and it is arguably more relevant today than ever before. Food sustainability and safety have been heavily prioritized by consumers, producers, and government entities alike. In this regard, filamentous fungi have always been a health hazard due to their contamination of the food substrate with mycotoxins. Additionally, mycotoxins are proven resilient to technological processing. This study aims to identify the main mycotoxins that may occur in the meat and meat products "Farm to Fork" chain, along with their effect on the consumers' health, and also to identify effective methods of prevention through the use of essential oils (EO). At the same time, the antifungal and antimycotoxigenic potential of essential oils was considered in order to provide an overview of the subject. Targeting the main ways of meat products' contamination, the use of essential oils with proven in vitro or in situ efficacy against certain fungal species can be an effective alternative if all the associated challenges are addressed (e.g., application methods, suitability for certain products, toxicity).

Antioxidant, Anti-inflammatory, and Immunomodulatory Roles of Nonvitamin Antioxidants in Anti-SARS-CoV-2 Therapy.

Viral pathologies encompass activation of pro-oxidative pathways and inflammatory burst. Alleviating overproduction of reactive oxygen species and cytokine storm in COVID-19 is essential to counteract the immunogenic damage in endothelium and alveolar membranes. Antioxidants alleviate oxidative stress, cytokine storm, hyperinflammation, and diminish the risk of organ failure. Direct antiviral roles imply: impact on viral spike protein, interference with the ACE2 receptor, inhibition of dipeptidyl peptidase 4, transmembrane protease serine 2 or furin, and impact on of helicase, papain-like protease, 3-chyomotrypsin like protease, and RNA-dependent RNA polymerase. Prooxidative environment favors conformational changes in the receptor binding domain, promoting the affinity of the spike protein for the host receptor. Viral pathologies imply a vicious cycle, oxidative stress promoting inflammatory responses, and vice versa. The same was noticed with respect to the relationship antioxidant impairment-viral replication. Timing, dosage, pro-oxidative activities, mutual influences, and interference with other antioxidants should be carefully regarded. Deficiency is linked to illness severity.

Multivariate Risk Analysis of RAS, BRAF and EGFR Mutations Allelic Frequency and Coexistence as Colorectal Cancer Predictive Biomarkers.

BACKGROUND: Biomarker profiles should represent a coherent description of the colorectal cancer (CRC) stage and its predicted evolution. METHODS: Using droplet digital PCR, we detected the allelic frequencies (AF) of KRAS, NRAS, BRAF, and EGFR mutations from 60 tumors. We employed a pair-wise association approach to estimate the risk involving AF mutations as outcome variables for clinical data and as predicting variables for tumor-staging. We evaluated correlations between mutations of AFs and also between the mutations and histopathology features (tumor staging, inflammation, differentiation, and invasiveness). RESULTS: KRAS G12/G13 mutations were present in all patients. KRAS Q61 was significantly associated with poor differentiation, high desmoplastic reaction, invasiveness (ypT4), and metastasis (ypM1). NRAS and BRAF were associated with the right-side localization of tumors. Diabetic patients had a higher risk to exhibit NRAS G12/G13 mutations. BRAF and NRAS G12/G13 mutations co-existed in tumors with invasiveness limited to the submucosa. CONCLUSIONS: The associations we found and the mutational AF we reported may help to understand disease processes and may be considered as potential CCR biomarker candidates. In addition, we propose representative mutation panels associated with specific clinical and histopathological features of CRC, as a unique opportunity to refine the degree of personalization of CRC treatment.

Antioxidant, anti-inflammatory and immunomodulatory roles of vitamins in COVID-19 therapy.

oxidative stress is caused by an abundant generation of reactive oxygen species, associated to a diminished capacity of the endogenous systems of the organism to counteract them. Activation of pro-oxidative pathways and boosting of inflammatory cytokines are always encountered in viral infections, including SARS-CoV-2. So, the importance of counteracting cytokine storm in COVID-19 pathology is highly important, to hamper the immunogenic damage of the endothelium and alveolar membranes. Antioxidants prevent oxidative processes, by impeding radical species generation. It has been proved that vitamin intake lowers oxidative stress markers, alleviates cytokine storm and has a potential role in reducing disease severity, by lowering pro-inflammatory cytokines, hampering hyperinflammation and organ failure. For the approached compounds, direct antiviral roles are also discussed in this review, as these activities encompass secretion of antiviral peptides, modulation of angiotensin-converting enzyme 2 receptor expression and interaction with spike protein, inactivation of furin protease, or inhibition of pathogen replication by nucleic acid impairment induction. Vitamin administration results in beneficial effects. Nevertheless, timing, dosage and mutual influences of these micronutrients should be carefullly regarded.

Composition-Based Risk Estimation of Mycotoxins in Dry Dog Foods.

The risk of mycotoxins co-occurrence in extrusion-produced dry foods increases due to their composition based on various grains and vegetables. This study aimed to validate a risk estimation for the association between ingredients and the ELISA-detected levels of DON, FUM, ZEA, AFs, T2, and OTA in 34 dry dog food products. The main ingredients were corn, beet, and oil of different origins (of equal frequency, 79.41%), rice (67.6%), and wheat (50%). DON and FUM had the strongest positive correlation (0.635, p = 0.001). The presence of corn in the sample composition increased the median DON and ZEA levels, respectively, by 99.45 µg/kg and 65.64 µg/kg, p = 0.011. In addition to DON and ZEA levels, integral corn presence increased the FUM median levels by 886.61 µg/kg, p = 0.005. For corn gluten flour-containing samples, DON, FUM, and ZEA median differences still existed, and OTA levels also differed by 1.99 µg/kg, p < 0.001. Corn gluten flour presence was strongly associated with DON levels > 403.06 µg/kg (OR = 38.4, RR = 9.90, p = 0.002), FUM levels > 1097.56 µg/kg (OR = 5.56, RR = 1.45, p = 0.048), ZEA levels > 136.88 µg/kg (OR = 23.00, RR = 3.09, p = 0.002), and OTA levels > 3.93 µg/kg (OR = 24.00, RR = 3.09, p = 0.002). Our results suggest that some ingredients or combinations should be avoided due to their risk of increasing mycotoxin levels.

Key biomarkers within the colorectal cancer related inflammatory microenvironment.

Therapeutic approaches focused on the inflammatory microenvironment are currently gaining more support, as biomolecules involved in the inflammatory colorectal cancer (CRC) tumor microenvironment are being explored. We analyzed tumor and paired normal tissue samples from CRC patients (n = 22) whom underwent tumor resection surgery. We assessed 39 inflammation-involved biomolecules (multiplex magnetic bead-based immunoassay), CEA and CA19-9 (ELISA assay) and the tissue expression levels of occludin and also pErk, STAT1 and STAT3 transcriptional factors (western blot). Tumor staging has been established by histopathological evaluation of HE stained tumor tissue sections. We report 32 biomarkers displaying statistically significant differences in tumor vs. control. Additionally, positive statistical biomarker correlations were found between MMP2-IL8 and BAFF-IL8 (Pearson correlation coefficients > 0.751), while APRIL-MMP2, APRIL-BAFF and APRIL-IL8 were negatively correlated (correlation coefficients < - 0.650). While APRIL, BAFF, IL8 and MMP2 did not modulate with tumor stage, they were inversely related to the immune infiltrate level and CD163 tissue expression. We conclude that the significantly decreased APRIL and increased BAFF, IL8 and MMP2 expression were tumor-specific and deserve consideration in the development of new treatments. Also, the positive correlation between Chitinase 3-like 1 and IL8 (0.57) or MMP2 (0.50) suggest a role in tumor growth and metastasis pathways.

Oxidative stress mitigation by antioxidants - An overview on their chemistry and influences on health status.

The present review paper focuses on the chemistry of oxidative stress mitigation by antioxidants. Oxidative stress is understood as a lack of balance between the pro-oxidant and the antioxidant species. Reactive oxygen species in limited amounts are necessary for cell homeostasis and redox signaling. Excessive reactive oxygenated/nitrogenated species production, which counteracts the organism's defense systems, is known as oxidative stress. Sustained attack of endogenous and exogenous ROS results in conformational and oxidative alterations in key biomolecules. Chronic oxidative stress is associated with oxidative modifications occurring in key biomolecules: lipid peroxidation, protein carbonylation, carbonyl (aldehyde/ketone) adduct formation, nitration, sulfoxidation, DNA impairment such strand breaks or nucleobase oxidation. Oxidative stress is tightly linked to the development of cancer, diabetes, neurodegeneration, cardiovascular diseases, rheumatoid arthritis, kidney disease, eye disease. The deleterious action of reactive oxygenated species and their role in the onset and progression of pathologies are discussed. The results of oxidative attack become themselves sources of oxidative stress, becoming part of a vicious cycle that amplifies oxidative impairment. The term antioxidant refers to a compound that is able to impede or retard oxidation, acting at a lower concentration compared to that of the protected substrate. Antioxidant intervention against the radicalic lipid peroxidation can involve different mechanisms. Chain breaking antioxidants are called primary antioxidants, acting by scavenging radical species, converting them into more stable radicals or non-radical species. Secondary antioxidants quench singlet oxygen, decompose peroxides, chelate prooxidative metal ions, inhibit oxidative enzymes. Moreover, four reactivity-based lines of defense have been identified: preventative antioxidants, radical scavengers, repair antioxidants, and those relying on adaptation mechanisms. The specific mechanism of a series of endogenous and exogenous antioxidants in particular aspects of oxidative stress, is detailed. The final section resumes critical conclusions regarding antioxidant supplementation.

Amorphous Silica Nanoparticles Obtained by Laser Ablation Induce Inflammatory Response in Human Lung Fibroblasts.

Silica nanoparticles (SiO2 NPs) represent environmentally born nanomaterials that are used in multiple biomedical applications. Our aim was to study the amorphous SiO2 NP-induced inflammatory response in MRC-5 human lung fibroblasts up to 72 hours of exposure. The intracellular distribution of SiO2 NPs was measured by transmission electron microscopy (TEM). The lactate dehydrogenase (LDH) test was used for cellular viability evaluation. We have also investigated the lysosomes formation, protein expression of interleukins (IL-1ß, IL-2, IL-6, IL-8, and IL-18), COX-2, Nrf2, TNF-α, and nitric oxide (NO) production. Our results showed that the level of lysosomes increased in time after exposure to the SiO2 NPs. The expressions of interleukins and COX-2 were upregulated, whereas the expressions and activities of MMP-2 and MMP-9 decreased in a time-dependent manner. Our findings demonstrated that the exposure of MRC-5 cells to 62.5 µg/mL of SiO2 NPs induced an inflammatory response.

RAGE and TGF-ß1 Cross-Talk Regulate Extracellular Matrix Turnover and Cytokine Synthesis in AGEs Exposed Fibroblast Cells.

AGEs accumulation in the skin affects extracellular matrix (ECM) turnover and triggers diabetes associated skin conditions and accelerated skin aging. The receptor of AGEs (RAGE) has an essential contribution to cellular dysfunction driven by chronic inflammatory responses while TGF-ß1 is critical in both dermal homeostasis and inflammation. We investigated the contribution of RAGE and TGF-ß1 to the modulation of inflammatory response and ECM turnover in AGEs milieu, using a normal fibroblast cell line. RAGE, TGF-ß1, collagen I and III gene and protein expression were upregulated after exposure to AGEs-BSA, and MMP-2 was activated. AGEs-RAGE was pivotal in NF-κB dependent collagen I expression and joined with TGF-ß1 to stimulate collagen III expression, probably via ERK1/2 signaling. AGEs-RAGE axis induced upregulation of TGF-ß1, TNF-α and IL-8 cytokines. TNF-α and IL-8 were subjected to TGF-ß1 negative regulation. RAGE's proinflammatory signaling also antagonized AGEs-TGF-ß1 induced fibroblast contraction, suggesting the existence of an inhibitory cross-talk mechanism between TGF-ß1 and RAGE signaling. RAGE and TGF-ß1 stimulated anti-inflammatory cytokines IL-2 and IL-4 expression. GM-CSF and IL-6 expression appeared to be dependent only on TGF-ß1 signaling. Our data also indicated that IFN-γ upregulated in AGEs-BSA milieu in a RAGE and TGF-ß1 independent mechanism. Our findings raise the possibility that RAGE and TGF-ß1 are both involved in fibrosis development in a complex cross-talk mechanism, while also acting on their own individual targets. This study contributes to the understanding of impaired wound healing associated with diabetes complications.

AGEs-Induced IL-6 Synthesis Precedes RAGE Up-Regulation in HEK 293 Cells: An Alternative Inflammatory Mechanism?

Advanced glycation end products (AGEs) can activate the inflammatory pathways involved in diabetic nephropathy. Understanding these molecular pathways could contribute to therapeutic strategies for diabetes complications. We evaluated the modulation of inflammatory and oxidative markers, as well as the protective mechanisms employed by human embryonic kidney cells (HEK 293) upon exposure to 200 µg/mL bovine serum albumine (BSA) or AGEs-BSA for 12, 24 and 48 h. The mRNA and protein expression levels of AGEs receptor (RAGE) and heat shock proteins (HSPs) 27, 60 and 70, the activity of antioxidant enzymes and the expression levels of eight cytokines were analysed. Cell damage via oxidative mechanisms was evaluated by glutathione and malondialdehyde levels. The data revealed two different time scale responses. First, the up-regulation of interleukin-6 (IL-6), HSP 27 and high catalase activity were detected as early as 12 h after exposure to AGEs-BSA, while the second response, after 24 h, consisted of NF-κB p65, RAGE, HSP 70 and inflammatory cytokine up-regulation, glutathione depletion, malondialdehyde increase and the activation of antioxidant enzymes. IL-6 might be important in the early ignition of inflammatory responses, while the cellular redox imbalance, RAGE activation and NF-κB p65 increased expression further enhance inflammatory signals in HEK 293 cells.

Complex responses to Si quantum dots accumulation in carp liver tissue: Beyond oxidative stress.

The use of quantum dots (QDs) in biomedical applications is limited due to their inherent toxicity caused by the heavy metal core of the particles. Consequently, silicon-based QDs are expected to display diminished toxicity. We investigated the in vivo effects induced by Si/SiO2 QDs intraperitoneally injected in crucian carp liver. The QDs contained a crystalline Si core encased in a SiO2 shell, with a size between 2.75 and 11.25nm and possess intrinsic fluorescence (Ex 325nm/Em ∼690nm). Tissue fluorescence microscopy analysis revealed the presence of QDs in the liver for at least 2weeks after injection. Although protein and lipid oxidative stress markers showed the onset of oxidative stress, the hepatic tissue exhibited significant antioxidant adaptations (increase of antioxidant enzymes, recovery of glutathione levels), sustained by the activation of Hsp30 and Hsp70 chaperoning proteins. The increased activity of cyclooxigenase-2 (COX-2) and matrix metalloproteinases (MMPs) support the idea that Si/SiO2 QDs have a potential to induce inflammatory response, a scenario also indicated by the profile of Hsp60 and Hsp90 heat shock proteins. MMPs profile and the recovery of oxidative stress markers suggested a tissue remodelation phase after 3weeks from QDs administration.

Extracellular matrix is modulated in advanced glycation end products milieu via a RAGE receptor dependent pathway boosted by transforming growth factor-ß1 RAGE.

BACKGROUND: Interstitial fibrosis is induced by imbalances in extracellular matrix homeostasis. Advanced glycation end products (AGEs) can bind and activate the receptor for AGEs (RAGE), which is involved in diabetic nephropathy. We set out to identify the role of AGEs in producing alterations leading to matrix hypertrophy and the pathway through which aminoguanidine, as well as anti-RAGE and anti-transforming growth factor (TGF)-ß1 antibody treatments could prevent these modifications. METHODS: Human embryonic kidney (HEK-293) cells were exposed to glycated bovine serum albumin (AGE-BSA) and co-treated with neutralizing antibodies or aminoguanidine. The effects on the transcriptional and translational levels of RAGE, TGF-ß1 and collagen IV were evaluated, while metalloproteinase activity was assessed by gelatin zymography. RESULTS: AGE-BSA (200 µg/mL) upregulated RAGE's expression, while TGF-ß1 synthesis and the formation of its bioactive form were increased in a dose-dependent manner by AGEs. AGE-BSA exposure increased both matrix metalloproteinase (MMP) activity and collagen IV synthesis, boosted by TGF-ß1 upregulation. Aminoguanidine's effects revealed that small concentrations (10 µmol/L) enhance AGE-BSA effects, by increasing the expression of RAGE and TGF-ß1, while higher concentrations (100 µmol/L) contribute to their downregulation. CONCLUSIONS: Although AGEs regulate RAGE and TGF-ß1 by distinct pathways, RAGE activation leads to a further increase of TGF-ß1 levels. MMP-2 activity seems to rely on TGF-ß1, while MMP-9 was dependent on RAGE. These factors converge to control collagen IV turnover. Furthermore, although the antibody treatments might appear more efficient than AG in decreasing collagen IV levels, the cells compensate the RAGE and TGF-ß1 blockade by increasing the mRNA expression of these proteins.

Lipid peroxidation due to in vitro and in vivo exposure of biological samples to nanoparticles.

The increasing use of nanomaterials in biological applications raises numerous concerns about the dangers they might pose to living organisms. The rise in oxidative stress is usually the most readily observed effect induced by nanoparticles, with the measurement of lipid peroxidation levels being one of the most frequently used biological markers for its evaluation. Here, we describe the spectrophotometric and fluorimetric methods for determining the modifications of the malondialdehyde (MDA) level induced by many types of nanoparticles in in vitro and in vivo biological systems.

Interaction of silicon-based quantum dots with gibel carp liver: oxidative and structural modifications.

Quantum dots (QDs) interaction with living organisms is of central interest due to their various biological and medical applications. One of the most important mechanisms proposed for various silicon nanoparticle-mediated toxicity is oxidative stress. We investigated the basic processes of cellular damage by oxidative stress and tissue injury following QD accumulation in the gibel carp liver after intraperitoneal injection of a single dose of 2 mg/kg body weight Si/SiO2 QDs after 1, 3, and 7 days from their administration.QDs gradual accumulation was highlighted by fluorescence microscopy, and subsequent histological changes in the hepatic tissue were noted. After 1 and 3 days, QD-treated fish showed an increased number of macrophage clusters and fibrosis, while hepatocyte basophilia and isolated hepatolytic microlesions were observed only after substantial QDs accumulation in the liver parenchyma, at 7 days after IP injection.Induction of oxidative stress in fish liver was revealed by the formation of malondialdehyde and advanced oxidation protein products, as well as a decrease in protein thiol groups and reduced glutathione levels. The liver enzymatic antioxidant defense was modulated to maintain the redox status in response to the changes initiated by Si/SiO2 QDs. So, catalase and glutathione peroxidase activities were upregulated starting from the first day after injection, while the activity of superoxide dismutase increased only after 7 days. The oxidative damage that still occurred may impair the activity of more sensitive enzymes. A significant inhibition in glucose-6-phosphate dehydrogenase and glutathione-S-transferase activity was noted, while glutathione reductase remained unaltered.Taking into account that the reduced glutathione level had a deep decline and the level of lipid peroxidation products remained highly increased in the time interval we studied, it appears that the liver antioxidant defense of Carassius gibelio does not counteract the oxidative stress induced 7 days after silicon-based QDs exposure in an efficient manner.

Structural and oxidative changes in the kidney of crucian carp induced by silicon-based quantum dots.

Silicon-based quantum dots were intraperitoneally injected in Carassius auratus gibelio specimens and, over one week, the effects on renal tissue were investigated by following their distribution and histological effects, as well as antioxidative system modifications. After three and seven days, detached epithelial cells from the basal lamina, dilated tubules and debris in the lumen of tubules were observed. At day 7, nephrogenesis was noticed. The reduced glutathione (GSH) concentration decreased in the first three days and started to rise later on. The superoxide dismutase (SOD) activity increased only after one week, whereas catalase (CAT) was up-regulated in a time-dependent manner. The activities of glutathione reductase (GR) and glutathione peroxidise (GPX) decreased dramatically by approximately 50% compared to control, whereas the glutathione-S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) increased significantly after 3 and 7 days of treatment. Oxidative modifications of proteins and the time-dependent increase of Hsp70 expression were also registered. Our data suggest that silicon-based quantum dots induced oxidative stress followed by structural damages. However, renal tissue is capable of restoring its integrity by nephron development.

Impact of silicon-based quantum dots on the antioxidative system in white muscle of Carassius auratus gibelio.

Silicon-based quantum dots were intraperitoneally injected in individuals of Carassius auratus gibelio. Their effects on white muscle were investigated by following their distribution and impact on the antioxidative system. The GSH level significantly increased after 1 and 3 days of exposure by, respectively, 85.3 and 25.4%. Seven days later, GSH levels were similar to control concentrations. MDA concentration rose after three days by 46.9% and remained at the same level after 7 days. Protein thiol levels significantly decreased by 6.7 and 8.1% after 3 and 7 days, whereas advanced oxidation protein products increased by 12.7, respectively, 28.1% in the same time intervals. The protein reactive carbonyl groups were raised only after the first day of exposure and returned to the control level later on. SOD specific activity increased up to 48% after 7 days, while CAT activity increased by 328, 176, and 26% after 1, 3, and 7 days of treatment. GST specific activity was up-regulated by 87, 18, and 9%, while GR activity increased by 68, 34, and 9%. G6PD activity was up-regulated by 12, 22, and 50%, whereas GPx activity raised by 75 and 109% compared to control after, respectively, 1, 3, and 7 days. Our results suggest that oxidative stress induced by silicon-based quantum dots was not strong enough to cause permanent damage in the white muscle of crucian carp.