Superoxide Dismutase Levels Research Articles

Citreoviridin induces apoptosis through oxidative damage and inflammatory response in PC-12 cells.

Citreoviridin (CIT) is a mycotoxin produced by various fungi. Although CIT has been reported to cause neurotoxicity, the molecular mechanism is poorly understood. Therefore, the aim of this study was to investigate the effects and molecular mechanisms of CIT in neurotoxicity. Different concentrations of CIT were treated to rat pheochromocytoma (PC-12 cells), and oxidative stress parameters, cytokine levels, and cell apoptosis were evaluated. CIT treatment (5 and 10μM) significantly induced PC-12 cell apoptosis and increased lactate dehydrogenase activity. Additionally, CIT treatment induced oxidative stress, as evidenced by a significant increase in intracellular levels of reactive oxygen species, malondialdehyde, and superoxide dismutase and a decrease in glutathione activity. Moreover, CIT treatment induced an inflammatory response, as evidenced by a significant increase in the intracellular levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1-beta in PC-12 cells. Furthermore, quantitative PCR and western blotting showed that CIT treatment increased both the protein and mRNA expression of GADD45α and p21 in PC-12 cells, suggesting that CIT may induce apoptosis by inhibiting cell cycle, blocking cell growth, and damaging DNA. Conclusively, this study contributes the understanding the toxicity mechanisms of CIT to nerve cells.

Evidence for endogenous hydrogen peroxide production by E. coli fatty acyl-CoA dehydrogenase.

Aerobic organisms continuously generate internal superoxide and hydrogen peroxide, which can damage enzymes and impair growth. To avoid this problem cells maintain high levels of superoxide dismutases, catalases, and peroxidases. Surprisingly, we do not know the primary sources of these reactive oxygen species (ROS) in living cells. However, in vitro studies have shown that flavoenzymes can inadvertently transfer electrons to oxygen. Therefore, it seems plausible that substantial ROS may be generated when large metabolic fluxes flow through flavoproteins. Such a situation may arise during the catabolism of fatty acids. Acyl-CoA dehydrogenase (FadE) is a flavoprotein involved in each turn of the beta-oxidation cycle. In the present study the catabolism of dodecanoic acid specifically impaired the growth of strains that lack enzymes to scavenge hydrogen peroxide. The defect was absent from fadE mutants. Direct measurements confirmed that the beta-oxidation pathway amplified the rate of intracellular hydrogen peroxide formation. Scavenging-proficient cells did not display the FadE-dependent growth defect. Those cells also did not induce the peroxide stress response during dodecanoate catabolism, indicating that the basal defenses are sufficient to cope with moderately elevated peroxide formation. In vitro work still is needed to test whether the ROS evolve specifically from the FadE flavin site and to determine whether superoxide as well as peroxide is released. At present such experiments are challenging because the natural redox partner of FadE has not been identified. This study supports the hypothesis that the degree of internal ROS production can depend upon the type of active metabolism inside cells.

Therapeutic effect of berberine against 5-fluorouracil induced ovarian toxicity in rats

ABSTRACT Berberine (BER) is a naturally occurring alkaloid with a multitude of beneficial effects on human health. Although it is one of the most studied phytochemicals, its curative effect against ovarian damage caused by 5-fluorouracil (5-FU) has not been demonstrated to date. The aim of this study was to investigate the possible protective effect of BER against 5-FU-induced ovotoxicity, focusing on its ability to attenuate oxidative stress, inflammation and apoptosis. The 30 female rats were randomly divided into five groups: Control, BER (2 mg/kg), 5-FU (100 mg/kg), 5-FU+BER (1 mg/kg) and 5-FU+BER (2 mg/kg). The levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT), 8-hydroxy-2’-deoxyguanosine (8-OHdG), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and caspase-3 were determined using spectrophotometric methods. In addition, ovarian samples were evaluated histopathologically using hematoxylin&eosin staining method. The MDA, TOS, 8-OHdG, IL-6, TNF-α and caspase-3 levels significantly increased by 5-FU administration. Also, we found that 5-FU significantly decreased TAS, SOD and CAT levels. Treatments with BER significantly attenuated the 5-FU-induced ovarian damage via increasing the antioxidant capacity and reducing the oxidative stress, inflammation and apoptosis in a dose-dependent manner. Moreover, the ovoprotective effect of BER was also confirmed by histopathological evaluation. BER may be evaluated as a potential candidate molecule to reduce 5-FU-induced ovarian toxicity.

Metabolomic analysis of the browning and browning inhibition pulp of Fuji apple at different ripening stages

Apples at different ripening stages display distinct processing properties and browning characteristics in products. This study aimed to identify differential metabolites and metabolic pathways of browning pulp and browning inhibition pulp of Fuji apple across four ripening stages (M1–M4), corresponding to days after full bloom (DAFB: 148, 155, 162, and 171). We investigated the physicochemical characteristics, browning-related enzyme activities, and metabolomic profiles of apples at the four stages, revealing defensive metabolic changes associated with browning throughout ripening. Specifically, the browning rate in apples increased with ripening, peaking before declining in the late stages, and exhibited positive correlations with activities of polyphenol oxidase (PPO), peroxidase (POD), and catalase (CAT), and negative correlations with superoxide dismutase (SOD), phenylalanine ammonia-lyase (PAL), and H2O2 levels. Metabolomic profiling identified 315, 393, and 243 distinct metabolites in fresh control (FC), browning pulp (BR), and browning-inhibited pulps (CM) of apple at the four ripening stages, respectively. KEGG enrichment analysis revealed that FC and BR of the four ripening apples were differentiated by phenylpropanoid biosynthesis, while CM was featured by flavonoid biosynthesis. The characterized differential metabolites in BR were changed to α-linolenic acid metabolism with ripening, while those in CM were from flavonoid and phenylpropanoid biosynthesis. Furthermore, the in-depth analysis revealed 40 significantly differential metabolites associated with amino acid, nucleotide, coenzyme, and vitamin metabolism, potentially modulating the stress-responsive cellular redox balance. This research provides critical insights for browning prevention in the processing of fruits at various ripening stages.

Assessing the chronic toxicity of climbazole to Daphnia magna: Physiological, biochemical, molecular, and reproductive perspectives

The widespread use of climbazole (CBZ) has led to its increased presence in aquatic environments, potentially threatening freshwater ecosystems. However, evidence regarding the harmful effects of CBZ on aquatic organisms remains limited. In this study, Daphnia magna was exposed to CBZ at concentrations of 0, 0.2, 20, and 200 μg/L for 21 days to evaluate its chronic toxicity through assessment of life-history traits, physiological parameters, biochemical analyses, and gene expression. The results indicated that CBZ exposure delayed the days to the first brood, reduced the frequency of molting per adult, decreased the offspring number at first brood, diminished the body length, and decreased both the total number of broods per female and the total number of offspring per female. Additionally, CBZ inhibited the swimming speed, filtration rate, and ingestion rate. Moreover, CBZ altered the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), while increasing malondialdehyde (MDA) levels. Gene expression analysis revealed varied responses in mRNA levels related to metabolic detoxification (cyp360a8, gst, and p-gp), digestive enzymes (α-amylase, α-esterase, and trypsin), energy (ak), oxygen transport (dhb), and reproduction (nvd, cyp314, ecr, vtg, and jhe) following CBZ exposure. These results indicate that the presence of CBZ in aquatic environments can induce toxicity by altering energy acquisition, supply, and metabolism; impairing metabolic detoxification pathways; eliciting oxidative stress; and causing reproductive toxicity in D. magna.

Exogenous Nitric Oxide Induces Pathogenicity of Alternaria alternata on Huangguan Pear Fruit by Regulating Reactive Oxygen Species Metabolism and Cell Wall Modification.

Black spot caused by Alternaria alternata is one of the most common postharvest diseases in fruit and vegetables. A comprehensive investigation into its pathogenicity mechanism is imperative in order to propose a targeted and effective control strategy. The effect of nitric oxide (NO) on the pathogenicity of A. alternata and its underlying mechanism was studied. The results showed that treatment with 0.5 mM L-1 of sodium nitroprusside (SNP) (NO donor) increased the lesion diameter of A. alternata in vivo and in vitro, which was 22.8% and 13.2% higher than that of the control, respectively. Exogenous NO treatment also induced endogenous NO accumulation by activating nitric oxide synthase (NOS). In addition, NO triggered an increase in reactive oxygen species (ROS) levels. NO enhanced activities and gene expression levels of NADPH oxidase (NOX), superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione peroxidase (GPX), and glutathione reductase (GR). Moreover, NO stimulated cell wall degrading enzymes by activating the corresponding gene expression in vivo and in vitro. These results suggested that exogenous NO promoted the pathogenicity of A. alternata by inducing ROS accumulation and activating antioxidants and cell wall degrading enzymes. The present results could establish a theoretical foundation for the targeted control of the black spot disease in pear fruit.

Effect of encapsulated Medinilla javanensis fruit extract on growth, protein digestibility and health of broilers

The study investigated the effect of encapsulated Medinilla javanensis fruit extract on performance, protein digestibility, and health of broilers. A total of 200 Cobb broiler chicks were divided into five treatments with four repetitions, including T0 (basal diet), T1 (basal diet + 200 mg/kg encapsulated Medinilla javanensis fruit extract), T2 (basal diet + 400 mg/kg encapsulated Medinilla javanensis fruit extract), T3 (basal diet + 600 mg/kg encapsulated Medinilla javanensis fruit extract), and T4 (basal diet + 800 mg/kg encapsulated Medinilla javanensis fruit extract). Sample collection was conducted on day 35 of age. Results showed that increased encapsulated Medinilla javanensis fruit extract levels in feed linearly increased (P<0.05) body weight, body weight gain, intestinal lactic acid bacteria counts, protein digestibility and serum superoxide dismutase levels, while linearly decreasing (P<0.05) feed conversion ratio, intestinal Escherichia coli counts, small intestinal pH values and serum malondialdehyde levels. In conclusion, encapsulated Medinilla javanensis fruit extract improved growth performance, protein digestibility intestinal health and antioxidant status of broilers. The encapsulated Medinilla javanensis fruit extract at a level of 600 mg/kg exerted the best performance and health of broilers.

Anti-fatigue effect of an enzymatically derived deer velvet extract through muscle damage recovery and improvement of antioxidant levels

Ethnopharmacological relevanceDeer velvet (DV) has been extensively used in traditional Oriental medicine to treat various diseases. Its pharmacological spectrum encompasses tonicity, longitudinal bone growth of adolescence, blood retention, hemopoiesis facilitation, enhancement of organ function, physical function improvement, and augmentation of physical vitality. Among its myriad effects, DV notably exhibits anti-fatigue properties; however, its specific mode of action is yet to be fully elucidated. Aim of the studyThis study was undertaken to investigate the anti-fatigue and exercise performance-enhancing effects of YC-1101(HENKIV®), an enzymatically derived DV extract, in C2C12 cell lines and forced swimming mouse models. Materials and methodsThe effect of YC-1101 on increasing cell growth and lowering lactate dehydrogenase (LDH) activity was assessed in C2C12. The antioxidative effects of YC-1101 and its mechanistic underpinnings were also evaluated in C2C12 cells. Moreover, mice were subjected to an exhaustive swimming test subsequent to 3 weeks of YC-1101 extract administration. Fatigue-associated biochemical parameters, such as LDH activity and lactate, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels, were measured in serum and muscle tissues. ResultsYC-1101 significantly promoted myoblast growth and reduced LDH activity, indicative of a cell-proliferative effect. Notably, free radical scavenging assays and analysis of reactive oxygen species production and antioxidant-related mRNA expression corroborated the significant involvement of YC-1101 in antioxidation, an important mechanism in anti-fatigue processes. Furthermore, animal experiments demonstrated prolonged swimming endurance and inhibition of muscle LDH accumulation in forced swimming mouse models. Serum biochemical analysis further revealed significant modulation of the expression of anti-fatigue-related biomarkers. Various bioactive low-molecular-weight DV peptides were enriched in YC-1101 compared to YHC-BE-2038 (a DV extract without enzymatic digestion). The anti-fatigue effect of YC-1101 was significantly stronger than that of YHC-BE-2038. ConclusionsThese findings suggest the potential of YC-1101 as a nutraceutical adjunct in ameliorating fatigue, concurrently facilitating muscle damage recovery, and exerting antioxidant effects via the nuclear factor E2-related factor 2-Kelch-like ECH-associated protein-1 pathway. It can be assumed that the complex action of low-molecular-weight DV peptides produced during the enzymatic degradation process was effective, and the further research is needed.

Hypoxia Activates FGF-23-ERK/MAPK Signaling Pathway in Ischemia-Reperfusion-Induced Acute Kidney Injury.

Both hypoxia and fibroblast growth factor-23 (FGF-23) are key factors in ischemia-reperfusion (I/R)-induced acute kidney injury (AKI). This study aimed to explore the relationship between hypoxia and FGF-23 in AKI. An I/R-AKI animal model was established using male BALB/c mice. HK-2 cells, a part of the human proximal tubular epithelial cell line, were subjected to hypoxia/reoxygenation (H/R). qPCR was used to measure FGF-23 and HIF1α, and ELISA was used to measure inflammatory and oxidative stress cytokines. Western blotting was used to measure the phosphorylation of extracellular signal-regulated kinase (ERK) level. In I/R mice, the levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), malondialdehyde (MDA), and the phosphorylation of ERK (p-ERK) were increased, whereas the levels of interleukin-10 (IL-10), superoxide dismutase (SOD), glutathione peroxidase (GPx), and klotho were decreased, compared to the sham-operated mice. Silencing the FGF-23 expression in I/R mice normalized the levels of IL-6, IL-10, TNF-α, MDA, SOD, GPx, and p-ERK. In HK-2 cells, hypoxia-reperfusion (H/R) elevated the levels of IL-6, TNF-α, MDA, and p-ERK, but reduced IL-10, SOD, GPx, and klotho levels. Hypoxia induced apoptosis in HK-2 cells, but silencing of FGF-23 expression blocked the effects of hypoxia on cell apoptosis, pro-inflammatory factor levels, oxidative stress response, and p-ERK levels. FGF-23 is a key molecule in AKI, and hypoxia plays a crucial role in AKI by inducing cell apoptosis; however, its role is regulated by FGF-23. FGF-23 affects oxidative stress and the inflammatory response of kidney tissues by activating the ERK/mitogen-activated protein kinase (MAPK) signaling pathway.

Supplementing exogenous xylanase improves the liver antioxidant capacity and immune response of Tibetan sheep fed wheat-based diets

Xylanase is a heteropolysaccharide found in the plant cell wall, which aids in the absorption and utilisation of nutrients. When embedded in animal feed, it enhances nutrient availability, leading to improved animal performance. The aim of this study was to explore the effect of xylanase supplementation in wheat-based feeds on the hepatic development, antioxidant capacity, and immune response in Tibetan sheep. Sixty healthy, weaned, non-neutered male lambs (19.35 ± 2.18 kg) were randomly assigned to two equal groups (n = 30 per group). Dietary treatments were: basal diet (H group), and basal diet with 0.2% xylanase supplementation (E group). After a 10–day adaptation period, the feeding trial was carried out for 90 days. The live weight, morphology, antioxidant capacity and immune response were measured. The differential genes in liver were identified by RNA-sequencing. Our results showed that the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were significantly higher in E group than in H group (p < 0.05). Enzyme-linked immunosorbent assay (ELISA) revealed that immunoglobulin A (IgA), IgM, and IgG were significantly higher in E group than in H group (p < 0.05). The hepatocytes of sheep fed xylanase diet showed arranged radially into hepatic plates cantered around the central vein, and the plates linked with each other to form a lost-like structure. A total of 4,509 differential genes (DEGs) were identified, among which 4,427 were up-regulated and 82 down-regulated. Additionally, the expression of antioxidant-related genes in cluding catalase (CAT), superoxide dismutase 1 (SOD1), oxidation resistance 1 (OXR1) and glutathione peroxidase 2 (GPX2), and immunity-related gene including mitogen-activated protein kinase 1 (MAPK1), signal transducer and activator of transcription 5B (STAT5B), janus kinase 3 (JAK3) and jun proto-oncogene (JUN) were verified using the quantitative reverse transcription polymerase chain reaction (qRT-PCR). Conclusion: In conclusion, dietary 0.2% xylanase supplementation promoted hepatic antioxidant capacity and immune response via modulating the expression of functional genes in Tibetan sheep.

Efficacy of multimodal analgesia based on the concept of enhanced recovery after surgery in laparoscopic radical gastrectomy for gastric cancer

Objective: To explore the effect of multimodal analgesia based on the concept of enhanced recovery after surgery (ERAS) in patients undergoing laparoscopic radical gastrectomy (LRG) for gastric cancer (GC). Methods: Clinical data of 128 patients undergoing LRG for GC, admitted to Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from March 2021 to March 2022, were retrospectively analyzed. Among them, 66 patients received a multimodal analgesic management based on ERAS (ERAS group), and 62 patients were treated with conventional mode of analgesia (control group). Pain levels, rehabilitation status, as well as inflammatory factors and stress response indicators before and after surgery were compared between the two groups. Results: There was no significant difference in baseline data between the two groups (P&gt;0.05). The postoperative pain and recovery in the ERAS group were better than those in the control group (P&lt;0.05). After the surgery, serum levels of tumor necrosis factor-alpha (TNF-α), Interleukin 6 (IL-6), and C-reactive protein (CRP) in both groups increased compared to before the surgery, but were significantly lower in the ERAS group compared to the control group (P&lt;0.05). After the surgery, serum malondialdehyde (MDA) and xanthine oxidase (XOD) levels in both groups increased, while superoxide dismutase (SOD) levels decreased compared to preoperative levels. The observed postoperative levels of serum MDA and XOD were significantly lower in the ERAS group, while the postoperative SOD levels were higher compared to the control group (P&lt;0.05). Conclusions: Patients undergoing LRG for GC can benefit from a multimodal pain management plan based on ERAS to reduce postoperative pain, alleviate inflammation, stress responses, and shorten the postoperative recovery process. doi: https://doi.org/10.12669/pjms.40.10.10088 How to cite this: Xu L, Yao L, Qin J, Xu H. Efficacy of multimodal analgesia based on the concept of enhanced recovery after surgery in laparoscopic radical gastrectomy for gastric cancer. Pak J Med Sci. 2024;40(10):2190-2195. doi: https://doi.org/10.12669/pjms.40.10.10088 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Ficus carica Puree Exerts a Higher Antioxidative Profile in Hypoxic Lungs after Intermittently Inducing Hypoxia in Sprague–Dawley Rats

Abstract Background: The body produces more hypoxia-inducible factor and reactive oxygen species in response to hypoxic situations because they cause unbalanced oxygen levels. Ficus carica provides numerous benefits because of its high antioxidant and mineral content. Nevertheless, the mechanism by which F. carica consumption confers this protective benefit remains incompletely understood. Aim: This study aimed to evaluate how F. carica puree (FCP) can affect the antioxidant enzyme activity and malondialdehyde (MDA) levels in the lung by mitigating the effects of intermittent hypoxia (IH). Methods: Thirty Sprague–Dawley rats were divided into five groups negative control (NC), untreated; positive control (PC), treated with aquadest; FCP1; FCP2; and FCP3, which received FCP at doses of 1.25, 2.5, and 5 mL/200 g body weight. The treatment was administered for 4 weeks before inducing IH (10% O2 and 90% N2) into all groups (except NC) for 4 h for 7 days. Furthermore, hemoglobin (Hb) level, lung MDA level, and lung superoxide dismutase (SOD) enzyme activity were assessed. Results: The Hb level did not exhibit a significant increase under IH conditions. Conversely, the PC group exhibited the least activity of lung antioxidant enzymes and the highest lung MDA levels. In addition, the FCP intervention group exhibited lower MDA levels than the PC group and ameliorated relative lung weight loss. Conclusion: All FCP intervention groups showed lower MDA levels and higher SOD levels compared to the PC group, suggesting that FCP could mitigate the effects of hypoxia in rat lungs.

The effect of major depressive disorder comorbidity on ischemia-modified albumin levels, a marker of oxidative stress, and antioxidant defense system in patients with obsessive compulsive disorder.

The aim of this study was to examine the levels of oxidant and antioxidant markers in patients with obsessive-compulsive disorder (OCD) and to investigate whether these levels change in the presence of major depressive disorder (MDD) comorbidity. This study was completed with 23 OCD patients with MDD comorbidity (OCD+MDD), 21 OCD patients without MDD comorbidity (OCD-MDD) and 21 healthy controls. Oxidative stress levels of the cases' were determined by ischemia modified albumin (IMA) and malondialdehyde (MDA) measurements and antioxidant levels were determined by superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) measurements. One-way analysis of variance (ANOVA) and unpaired Student's t-test were used to compare the study groups. Post hoc Bonferroni test was used for the degree of significance between groups, and repeated measures analysis of covariance (ANCOVA) was used to investigate the effect of age and gender. IMA and MDA levels were significantly higher in the OCD group compared to the control group, and SOD, CAT and GSH-Px levels were lower in the OCD group compared to the control group (p<0.01). IMA levels were significantly higher in the OCD+MDD group compared to the OCD-MDD group, while SOD, CAT and GSH-Px levels were significantly lower in the OCD+MDD group compared to the OCD-MDD group (p<0101). MDA levels were significantly higher in the OCD+MDD group compared to the OCD-MDD group (p=0.009). When the entire OCD patient group was examined, significant, powerful, positive correlations were observed between Y-BOCS and HDRS scores and IMA and MDA, and significant powerful negative correlations between Y-BOCS and HDRS scores and SOD, CAT, and GSH-Px (p<0.001 for all). In OCD+MDD group, oxidative stress markers increased significantly in parallel with the severity of depression, while antioxidant levels decreased (p=0.003 for IMA, p<0.001 for others). We believe that parameters indicating impaired oxidant/antioxidant balance in patients with obsessive-compulsive disorder may help to elucidate the cause of the disease and may be potentially useful biomarkers in the diagnosis and determination of the severity of comorbid MDD.

Frequency-Dependent Antioxidant Responses in HT-1080 Human Fibrosarcoma Cells Exposed to Weak Radio Frequency Fields.

This study explores the complex relationship between radio frequency (RF) exposure and cancer cells, focusing on the HT-1080 human fibrosarcoma cell line. We investigated the modulation of reactive oxygen species (ROS) and key antioxidant enzymes, including superoxide dismutase (SOD), peroxidase, and glutathione (GSH), as well as mitochondrial superoxide levels and cell viability. Exposure to RF fields in the 2-5 MHz range at very weak intensities (20 nT) over 4 days resulted in distinct, frequency-specific cellular effects. Significant increases in SOD and GSH levels were observed at 4 and 4.5 MHz, accompanied by reduced mitochondrial superoxide levels and enhanced cell viability, suggesting improved mitochondrial function. In contrast, lower frequencies like 2.5 MHz induced oxidative stress, evidenced by GSH depletion and increased mitochondrial superoxide levels. The findings demonstrate that cancer cells exhibit frequency-specific sensitivity to RF fields even at intensities significantly below current safety standards, highlighting the need to reassess exposure limits. Additionally, our analysis of the radical pair mechanism (RPM) offers deeper insight into RF-induced cellular responses. The modulation of ROS and antioxidant enzyme activities is significant for cancer treatment and has broader implications for age-related diseases, where oxidative stress is a central factor in cellular degeneration. The findings propose that RF fields may serve as a therapeutic tool to selectively modulate oxidative stress and mitochondrial function in cancer cells, with antioxidants playing a key role in mitigating potential adverse effects.

Preliminary study on Cyclocodon lancifolius leaf blight and screening of Bacillus subtilis as a biocontrol agent.

This study aimed to identify the pathogen responsible for leaf blight in Cyclocodon lancifolius, investigate its biological characteristics, and identify effective synthetic fungicides. Additionally, this study examined changes in physiological and biochemical indices of leaves following pathogen infection and screened biocontrol bacteria that inhibit the pathogen growth, providing a scientific basis for preventing and managing leaf blight in C. lancifolius. Pathogens were isolated from the interface of healthy and infected leaf tissues and identified through morphological and molecular biological methods. Amplification and sequencing of three genomic DNA regions-internal transcribed spacer region, translation elongation factor 1-α, and glyceraldehyde-3-phosphate dehydrogenase of ribosomal DNA-were performed, followed by the construction of a phylogenetic tree. The biological characteristics of pathogens under various temperature and pH conditions and different nitrogen and carbon sources were analyzed using the mycelial growth rate method. The antifungal effects of 13 chemical agents were evaluated using the poisoned medium method and mycelial growth rate method. Changes in physiological and biochemical indicators post-infection were also assessed. An antagonistic experiment was conducted to screen for biocontrol bacteria. A total of 29 potential pathogenic strains were isolated from infected leaf tissues, with Koch's Postulates confirming Stemphylium lycopersici as a key pathogen causing the disease. Growth analysis of S. lycopersici revealed optimal growth at 20°C and pH 6, with lactose or maltose serving as the most suitable carbon source and histidine as the preferred nitrogen source. Among the 13 synthetic fungicides tested, strain DHY4 exhibited the greatest sensitivity to 400 g/L flusilazole. Significant differences (p < 0.05) were observed in superoxide dismutase, phenylalanine ammonia-lyase, peroxidase, polyphenol oxidase, catalase, and malondialdehyde levels between treated and control groups 3 days post-inoculation. The biocontrol strain DYHS2, identified as a strain of Bacillus subtilis, demonstrated an inhibition rate of 51.80% against S. lycopersici in dual-culture experiments and showed a relative inhibition rate of 78.82% in detached leaf assays. These findings provide valuable insights into the newly identified causal agent of leaf blight in C. lancifolius and its biological characteristics, underscoring the potential of B. subtilis DYHS2 and synthetic fungicides such as flusilazole as effective disease management strategies.

Flavonoids from Verbascum thapsus Protect Against Nephrotoxicity in Rats

General Background: Nephrotoxicity induced by carbon tetrachloride (CCl4) poses significant health risks, prompting the exploration of natural antioxidants for renal protection. Specific Background: Verbascum thapsus, a plant known for its flavonoid content, has shown potential in mitigating oxidative stress, but its specific protective effects against CCl4-induced nephrotoxicity remain under-investigated. Knowledge Gap: While previous studies have indicated antioxidant properties of flavonoids, their efficacy in renal preservation in vivo has not been fully elucidated. Aims: The study evaluated the antioxidative and nephroprotective properties of flavonoids from Verbascum thapsus leaves in a rat model of CCl4-induced nephrotoxicity.Results: Rats were divided into three groups: control, CCl4-treated, and flavonoid plus CCl4-treated. Biochemical analyses revealed that CCl4 significantly elevated malondialdehyde (MDA), urea, creatinine, and uric acid levels while decreasing superoxide dismutase (SOD) and glutathione (GSH) levels. Notably, flavonoid administration markedly reduced MDA, urea, creatinine, and uric acid levels and enhanced SOD and GSH levels compared to the CCl4-only group. Novelty: This study uniquely highlights the protective role of flavonoids from Verbascum thapsus against nephrotoxicity, demonstrating both their antioxidative capacity and renal preservation in an experimental model. Implications: The findings support the potential use of Verbascum thapsus as a therapeutic agent in the management of kidney diseases, suggesting further investigation into its application in clinical settings to address nephrotoxicity and related renal disorders. Highlights: Nephroprotective: Flavonoids significantly protect against CCl4-induced kidney damage. Biochemical Enhancement: Improved antioxidant levels; reduced harmful biochemical indicators. Therapeutic Potential: Supports natural treatments for kidney diseases. Keywords: Verbascum thapsus, flavonoids, nephrotoxicity, antioxidants, carbon tetrachloride

Doxorubicin Incorporation into Gold Nanoparticles: An In Vivo Study of Its Effects on Cardiac Tissue in Rats.

Gold nanoparticles (Au-NPs) have been explored as potential vectors for enhancing the antitumor efficacy of doxorubicin (DOX) while minimizing its cardiotoxic effects. However, the impacts of DOX Au-NPs on cardiac function and oxidative stress remain inadequately understood. This study aimed to explore the effects of DOX Au-NPs in comparison to free DOX, focusing on oxidative stress markers, inflammation, ultrastructural changes, and cardiac function. Male rats were divided into the following four groups: control, citrate Au-NPs, DOX, and DOX Au-NPs. Cardiac function was assessed using echocardiography, and oxidative stress was evaluated through Nrf2, malondialdehyde (MDA) and superoxide dismutase (SOD) levels, and the GSH/GSSG ratio. The ultrastructure of cardiac tissue was assessed by transmission electron microscopy (TEM). Rats treated with DOX Au-NPs exhibited significant cardiac dysfunction, as indicated by a reduction in fractional shortening and ejection fraction. Oxidative stress markers, including elevated MDA levels and a reduced GSH/GSSG ratio, were significantly worse in the DOX Au-NP group. SOD levels decreased, indicating compromised antioxidant defenses. Citrate Au-NPs also caused some alterations in cardiac function and ultrastructure but without other molecular alterations. DOX Au-NPs failed to mitigate cardiotoxicity, instead exacerbating oxidative stress and cardiac dysfunction. DOX Au-NPs possess cardiotoxic effects, necessitating further investigation into alternative nanoparticle formulations or therapeutic combinations to ensure both efficacy and safety in cancer treatment.

Oxidative damage biomarkers and antioxidant enzymes in saliva of patients with peri-implant diseases

Objectives8-hydroxydeoxyguanosine (8-OHdG) and Malondialdehyde (MDA) are commonly used as markers to evaluate oxidative DNA and Lipid damage in disorders including chronic inflammatory diseases. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) protect tissues against oxidative injury from free oxygen radicals generated by various metabolic processes. The aim of this study was to evaluate 8-OHdG and MDA levels, and SOD and GPx activities in whole saliva of patients with peri-implant diseases.Materials and methodsA cross-sectional study was conducted on a sum of 60 age gender balanced; peri-implantitis (n = 20), peri-mucositis (n = 20) and healthy (n = 20) individuals. Unstimulated whole saliva samples were collected and to determine the clinical condition of each subject; the plaque index (PI), gingival index (GI), peri-implant probing pocket depth (PIPD), peri-implant presence of bleeding on probing (BOP) (with/without suppuration) and radiographic signs of crestal bone loss (BL) were measured. The salivary 8-OHdG level was measured using the ELISA method. SOD, GPx activities and MDA levels were determined spectrophotometrically.ResultsA total of 60 individuals had evaluations of 318 implants. In comparison to the peri-mucositis and peri-implantitis groups, the healthy group had significantly lower PI and GI scores (p < 0.001). The PIPD value differed amongst the groups, with the peri-implantitis group having the highest value (p < 0.001). Compared to the peri-mucositis and control groups, the peri-implantitis group had a significantly higher BL score (p < 0.001 and p < 0.001, respectively). The peri-implantitis group showed a significantly higher 8-OHdG level (p < 0.001; p < 0.001 respectively) than the peri-mucositis and control groups. Compared to the peri-mucositis and control groups, the peri-implantitis group had a significantly higher MDA level (p < 0.001 and p < 0.001, respectively). The peri-implantitis group had a significantly higher SOD level (p < 0.001 and p < 0.001, respectively) in comparison to the peri-mucositis and control groups. There was no significant difference in GPx levels between the peri-mucositis and control groups (p > 0.05), while the peri-implantitis group had significantly lower GPx levels than the peri-mucositis and control groups (p < 0.001 and p < 0.001, respectively).ConclusionsElevated levels of oxidative stress in saliva may indicate the onset of pathological bone loss surrounding the implant and may be an indication of peri-implantitis.Clinical relevanceIn peri-implant diseases, changes may occur in the levels of 8-OHdG, MDA, SOD and GPx in saliva, which may lead to a deterioration in the oxidant/antioxidant balance.

Acute toxicity assessment and QSAR modeling of zebrafish embryos exposed to methyl paraben and its halogenated byproducts

Halogenated methyl parabens are formed readily during water chlorination, with or without bromide ion presence. However, research gaps persist in in vivo toxicological assessments of vertebrates exposed to halo-MePs. To address this gap, this study evaluated acute toxicities at 24−96 h-post-fertilization in zebrafish embryos exposed to methyl paraben and its mono- or di-halogenated derivatives, using various apical endpoints. Significant enhanced toxic effects were confirmed for halo-MePs compared to MeP on embryo coagulation (3–19 fold), heartbeat rate decrement (11–80 fold), deformity rate increment (9–68 fold), and hatching failure (4–33 fold), with parentheses indicating the determined toxic potency ratios. Moreover, halo-MePs showed a significantly higher increase in biochemical levels of reactive oxygen species, catalase, superoxide dismutase, and malondialdehyde, while acetylcholinesterase activity was inhibited compared to NT and MeP. The experimental toxic potencies (log(1/EC50 or LC50)) were compared with the predicted ones (log(1/EC50 or LC50, baseline)) using the baseline toxicity Quantitative Structure-Activity Relationship previously established for zebrafish embryos. Halo-MePs were specific (or reactive) toxicants based on their toxic ratios of more than 10 for apical endpoints including heartbeat rate, deformity rate, and hatching rate, while MeP acted as a baseline toxicant. Overall, this study presents the comprehensive toxicological assessment of halo-MePs in zebrafish embryos, contributing to an essential in vivo toxicity database for halogenated phenolic contaminants in aquatic ecosystems.

Investigating the protective effects of epigallocatechin-gallate against polystyrene microplastics-induced biochemical and hematological alterations in rats

BackgroundPolystyrene microplastics (PS-MPs) are widely used and found in drinking water and food, concerns have been raised about their potential health effects, especially in causing oxidative stress and inflammation in living organisms. ObjectivesThe aim of this study was to investigate the protective effects of epigallocatechin-gallate (EGCG), a natural antioxidant and anti-inflammatory compound, against PS-MPs-induced biochemical and hematological alterations in rats. MethodsMale Wistar rats were divided into four groups: control, EGCG-treated (80 mg∙ kg-1/d), PS-MPs-exposed (0.01 mg∙kg-1/d), and PS-MPs+EGCG-treated groups. PS-MPs were orally administered for 56 days, while EGCG was given concomitantly by gavage. At the end of the treatment period, blood samples were collected for hematological and biochemical analyses. Oxido-nitrergic stress markers, including malondialdehyde (MDA), nitric oxide (NO), reactive nitrogen species (RONS) and reduced glutathione (GSH), Superoxide dismutase (SOD), catalase (CAT), as well as inflammatory markers, such as tumor necrosis factor alpha (TNF-α), interferon gamma (IFY-γ) and interleukin-10 (IL-10), were also measured in serum. ResultsTreatment with PS-MPs caused a significant increase in MDA, RONS, NO levels and a decrease in SOD, CAT and GSH levels, indicating the induction of oxido-nitrergic stress. PS-MPs also caused an increase in the levels of TNF-α, IFY-γ, MPO and decreased IL-10, indicating the induction of inflammation. Additionally, PS-MPs caused alterations in hematological and serum transaminase parameters, including a decrease in red blood cell count, hemoglobin, and hematocrit levels, neutrophil and eaosinophil and an increase in white blood cell count, lymphocyte count, AST, ALT, ALP, LDH and GGT. PS-MPs also caused disturbances in electrolyte balance and renal function markers. However, treatment with EGCG significantly attenuated these alterations induced by PS-MPs, indicating its protective effects. ConclusionThe results of this study demonstrate that EGCG can protect against PS-MPs-induced biochemical and hematological alterations in rats, possibly through its antioxidant and anti-inflammatory properties.