SOD Activity Research Articles

Cytotoxicity of single and binary mixtures of copper and silica nanoparticles exposed to Nitzschia closterium f. minutissima.

A large number of nanoparticles are produced and enter the aquatic environment, where they interact with each other, posing a potential threat to aquatic organisms. The toxicity of two types of nanoparticles (nCu and nSiO2) on Nitzschia closterium f. minutissima (N. closterium f. minutissima) was investigated in this study by examining changes in microalgal cell density, instantaneous fluorescence rate (Ft), and a range of antioxidant parameters in the cells. It was found that both nCu and nSiO2 showed time- and concentration-dependent toxic effects on N. closterium f. minutissima. nSiO2 could promote microalgae growth at low concentrations by providing Si, an essential element for the synthesis of siliceous shells. As the exposure time increased, both the growth and photosynthetic efficiency of the microalgae were inhibited. Nanoparticles also produced oxidative stress and caused lipid peroxidation in the microalgae. In the meantime, SOD and CAT activity were altered to protect cells from oxidative damage. Inverted biomicroscopy images showed that the microalgae enhanced their cell size to adapt to the environmental stress as exposed to 1 mg/L nCu. Scanning electron microscope (SEM) images showed that 10 mg/L nSiO2 could adsorb nCu and reduce the toxic effect of nCu on the microalgae, while 30 mg/L nSiO2 caused mechanical damage to microalgal cells and accelerated the internalization of nanoparticles and Cu2+ in the cells.

TBBPA caused multiple intestinal injuries via ROS/NF-κB signal in common carp

Tetrabromobisphenol A (TBBPA) is an aquatic environment's prevalent pollutant, posing a great threat to the health of aquatic animals. The intestine is a key organ for nutrient absorption as well as an important barrier to prevent pollutants from invading the body of fish. Exploring the effects of pollutants on the intestine is of great significance for maintaining fish health. Therefore, the purpose of this study was to assess the toxic effects of TBBPA on the intestine of Cyprinus carpio L. (common carp) by establishing models of common carp and primary intestinal epithelial cells exposed to TBBPA. Histological observation revealed that TBBPA exposure led to damage in the intestinal mucosa and breakage of intestinal villi. Detection of oxidative stress levels showed that TBBPA increased the levels of ROS and MDA, and decreased the activity of SOD, CAT, GSH-PX, and T-AOC in intestinal tissue and cells. Observation of inflammatory factor levels revealed that TBBPA upregulated the mRNA levels of inflammatory factors (IL-6, TNF-α, IL-1β, NF-κB p65 and IκBα). ELISA and western blotting results were consistent with the mRNA results. Moreover, TBBPA induced cell death, as evidenced by TUNEL staining and flow cytometry and confirmed by increasing levels of Bax, Cas-3, Cyt C, RIP1, RIP3, and MLKL, together with decreasing the levels of Bcl-2. TBBPA also destroyed the intestinal tight junction by reducing the mRNA and protein levels of claudin-1, ZO-1, and occludin. In summary, this study reveals that TBBPA caused intestinal injuries, inducing oxidative stress, inflammation, cell death, and tight junction disruption via ROS/NF-κB signal in common carp.

18β-Glycyrrhetinic Acid Mitigates Bisphenol A-induced Liver and Renal Damage: Inhibition of TNF-α/NF-κB/p38-MAPK, JAK1/STAT1 Pathways, Oxidative Stress and Apoptosis.

Bisphenol A (BPA) has been commonly used in various consumer products, including water bottles, food containers, and canned food linings. However, there are concerns about its potential toxicity to human health, particularly its impact on the liver and kidneys. The objective of this research was to investigate the potential ameliorative effects of 18β-glycyrrhetinic acid (GA) against BPA-induced liver and kidney toxicities. The animals were supplemented with BPA (250 mg/kg b.w.) alone or with GA (50 and 100 mg/kg b.w.) for 14 days. GA treatment alleviated the BPA-induced hepato-renal tissue injuries through reducing the serum ALT, AST and ALP levels, and urea and creatinine levels. GA co-treatment also increased activities of SOD, CAT and GPx enzymes and levels of GSH, and suppressed MDA levels in BPA induced tissues. BPA also induced inflammation by increasing the levels of TNF-α, NF-κB, JAK1, STAT1, P38 MAPK and JNK in liver and kidney tissues and GA treatment ameliorated these effects. BPA triggered apoptosis by increasing caspase-3, bax, and cytochrome c at protein levels and also by decreasing the antiapoptotic bcl-2 level. However, treatment with GA (50 and 100 mg/kg) decreased apoptosis. Overall, our results have revealed the potential ameliorative mechanisms of GA, as a possible agent for BPA-induced liver and kidney toxicities.

DEHP-mediated oxidative stress leads to impaired testosterone synthesis in Leydig cells through the cAMP/PKA/SF-1/StAR pathway.

Leydig cells (LCs) injury is often irreversible upon discovery; hence, early identification of risk factors for injury is crucial. The ubiquitous plasticizer di-2-ethylhexyl phthalate (DEHP) in the environment has been shown to potentially cause damage to LCs. However, the underlying mechanisms remain unclear. The present study utilized scRNA-seq analysis, the advantage of which is the ability to explore the characteristics of various testicular cells, combined with studies in vitro and in vivo, to assay the changes in and damage processes of LCs during DEHP exposure. We found that DEHP disrupted the structure and function of LCs. GO analysis suggested that a series of pathways changed, among which the most significant were the "steroid synthesis" and "oxidative stress" pathways. Moreover, DEHP dramatically changed the manner of interaction between LCs and other cells, and the most significant type was the cell-cell contact, which included NECTIN, APP, CADM, and CD39. In addition, the activity of multiple transcription factors (TFs) decreased after DEHP exposure, and the activity of steroidogenic factor 1 (SF-1, Nr5a1) was the most obviously altered. Next, we found that the LCs region indeed experienced oxidative stress, including increased ROS signals, the decreased SOD activity and T-AOC, and increased concentration of 8-OHdG and MDA content. The testosterone level, as well as the expression of StAR, P450scc, and 3β-HSD, was also reduced. To study the association between testosterone synthesis and oxidative stress, the antioxidants N-acetyl-L-cysteine (NAC) and H2O2 were used, and we found that mono-2-ethylhexyl ester (MEHP, a major biometabolite of DEHP) disrupted testosterone synthesis through the inhibition of the cAMP/PKA/SF-1/StAR pathway by inducing oxidative stress. Our study provides new insights into the role and mechanisms of DEHP in LCs injury.

Renoprotective Effect of Berberine in Cisplatin-Induced Acute Kidney Injury: Role of Klotho and the AMPK/mTOR/ULK1/Beclin-1 Pathway.

Cisplatin (Cisp.) is a potent cancer drug, but its use is limited by acute kidney injury (AKI). Autophagy, a process that removes damaged proteins and maintains cellular homeostasis, has been shown to alleviate Cisp-induced AKI. The balance between autophagy and apoptosis is crucial to kidney protection. Treatment with Berberine, known for its antioxidant and anti-inflammatory effects in nephrotoxicity models, was studied for its potential to enhance autophagy in Cisp-induced AKI. Treatment with Berberine (Berb) upregulated Klotho gene expression, enhancing autophagy as indicated by elevated protein levels of pS486-AMPK, pS638-ULK1, and Beclin-1, accompanied by a decrease in pS248-mTOR protein expression. Also, Berb mitigated oxidative stress by reducing elevated MDA levels and boosting SOD activity, which in turn suppressed inflammation by down-regulating HMGB1 and RAGE gene expression, as well as reducing pS536-NF-κB and IL-6 protein contents. Additionally, Berb reduced apoptosis by increasing Bcl-2 and decreasing Bax. This coordinated action preserved kidney function, evidenced by reductions in early injury markers (cystatin C, KIM-1, NGAL) and late markers (creatinine, BUN), along with attenuation of histopathological alterations. The use 3-MA, autophagy inhibitor, nullified these protective effects, highlighting Berb's role in promoting autophagy, reducing oxidative stress, inflammation, and apoptosis, and preserving renal health in Cisp-induced AKI.

Effects of Turmeric and Rosemary Extract on Oxidative Stress Markers in Goats

Background: Due to their versatility, goats are becoming popular as livestock on commercial farms. To obtain a high productivity, the maintenance of homeostasis in these organisms is needed. Some supplements that could help improve their health state have been tested recently. The study examines the effects of a turmeric–rosemary extract mixture on the antioxidant status of the blood of young castrated bucks. Results: Supplementation lowered lipoperoxidation and increased TAC, probably due to the improved neutralization of reactive oxygen species (ROS) by enhanced antioxidant pathways. Despite lowering lipid peroxidation, these products can increase protein oxidation. Thus, while enhancing lipid defense mechanisms may reduce lipid peroxidation, it may also increase the level of OMP, probably due to the accumulation of lipid peroxidation metabolites. The activities of SOD, GPx, and GR remained unchanged, whereas CAT activity decreased. CP, ALT, and AST remained stable, suggesting no adverse effects on key markers of liver function. Conclusions: The high antioxidant potential observed after supplementation indicates that the turmeric–rosemary extract mixture elicited a favorable biochemical response; the supplemented compounds effectively enhanced antioxidant defenses (by improving the neutralization of ROS) without negatively affecting liver enzyme activities. Turmeric–rosemary dry extract supplementation can help with homeostasis maintenance in goat organisms and, consequently, improve their productivity.

Typical tetra-mediated signaling and plant architectural changes regulate salt-stress tolerance in indica rice genotypes.

Upon exposure to salt stress, calcium signaling in plants activates various stress-responsive genes and proteins along with enhancement in antioxidant defense to eventually regulate the cellular homeostasis for reducing cytosolic sodium levels. The coordination among the calcium signaling molecules and transporters plays a crucial role in salinity tolerance. In the present study, twenty-one diverse indigenous rice genotypes were evaluated for salt tolerance during the early seedling stage, and out of that nine genotypes were further selected for physio-biochemical study. Further analysis identified potential salt-tolerant and salt-sensitive genotypes with tolerant lines exhibiting lower Na+/K+ ratio. Plant phenotype clearly documented the root architectural changes among the most salt-tolerant and sensitive genotypes, while the histo-biochemical DAB and NBT staining and in-gel SOD activity clearly revealed the differential ROS accumulation between the contrasting genotypes and their antioxidant activity. Ultrastructural study depicted stronger UV autofluorescence in the hypodermal and vascular bundle regions, while phloroglucinol staining displayed intense coloration in the vascular bundle region of Bhutmuri, the salt-tolerant genotype, compared to Manipuri Black, the salt-sensitive one showing differential lignification among the contrasting genotype to combat salt stress. Based on expression study, our proposed model depicted immediate upregulation (short-term) of OsSOS3 and OsNHX1 along with gradual upregulation of OsHKT and downregulation of OsSOS1 throughout the stress period to protect the tolerant plant through signaling cascade, while the inadequate upregulation of OsSOS3, OsNHX1, and OsHKT under early stress, coupled with poor coordination between the expression of OsSOS1 and OsSOS3 genes, makes the plant salt sensitive.

Silencing superoxide dismutases (SOD1&SOD2) potentiates ROS-induced apoptosis in chordoma cells.

Chordoma, characterized as a slow growing yet locally invasive and destructive bone tumor mainly emerging in the sacrum and clivus, presents a unique challenge due to its rarity, hampering the development of effective treatment strategies. Comprehensive understanding of tumor biology is crucial to suggest novel treatment modalities. Reactive oxygen species (ROS), a family of chemically reactive and unstable oxygen derivatives, are controlled by an intracellular antioxidant system to maintain homeostasis. Higher doses of ROS levels have been associated with the oxidative stress-induced tumor cell death, highlighting the potential of fine-tuning ROS regulation as a target for cancer therapies. The association of ROS mechanism and chordoma remains to be elucidated. In this study, we investigated the effect of targeting the ROS mechanism in chordoma, focusing on superoxide dismutase 1 and superoxide dismutase 2. Two different chordoma datasets were used to assess oxidative stress-related genes. ROS levels and mitochondrial membrane potential (mtMP) in chordoma cells were measured. The gene expression levels of SOD1 and SOD2 in chordoma patients were also evaluated. SOD2 and SOD1 targeted siRNAs were used to silence gene expression in chordoma cells, and quantitative real-time PCR (qRT-PCR) was used to compare gene expression levels. Apoptotic cell populations were determined using flow cytometry. The levels of ROS and mtMP were increased in chordoma cell lines compared to healthy nucleus pulposus cells. The chordoma omics data showed induced levels of SOD2. Chordoma tissues also showed high levels of the SOD2 gene. Silencing SOD2 and combined silencing of SOD2 and SOD1 expression increased ROS levels or mtMP, and both induced apoptosis in chordoma cells. ROS imbalance plays a role in chordoma pathogenesis. SOD2 and SOD1 might be key enzymes in chordoma to modulate ROS levels, and inhibiting the SOD2 and SOD1 activity might be a potential therapeutic target for chordoma treatment.

Paraquat neurotoxicity: Oxidative stress and neuronal dysfunction in the ascidian brain.

Paraquat (PQ) is a widely used herbicide; however, it has been linked to various diseases, including an increased risk of developing Parkinsonism. To study this, invertebrates such as ascidians have been used. They have a simple nervous system and are considered an emerging model for the study of neurodegenerative diseases. Here, we investigated the effects of PQ in the brain of the ascidian Styela plicata. We performed behavioral tests, assessed morphology, and monitored oxidative stress and the expression of tyrosine hydroxylase (TH) and caspase-3 (Casp 3) using immunofluorescence. In the presence of PQ, siphon movement was reduced and cortical thickness was increased. In addition, an observed increase in ROS was detected, along with attenuated SOD and CAT activities and increased LPO production. Interestingly, PQ downregulated the expression of TH and upregulated that of Casp 3. We conclude that PQ-induced oxidative stress leads to the death of catecholaminergic neurons in the S. plicata brain.

Effect of repeated sprint training in hypoxia on acute and chronic redox balance modulation

Little is known regarding the effects high-intensity training performed in hypoxia on the oxidative stress and antioxidant systems. The aim of this study was to assess the potential effect of 4 weeks of repeated sprint training in hypoxia (RSH) on the redox balance. Forty male well-trained cyclists were matched into two different interventions (RSH, n = 20) or in normoxia, RSN, n = 20) and tested twice (before (Pre-) and after (Post-) a 4-week of training) for performance (repeated sprint ability (RSA) test), oxidative stress, and antioxidant status. Antioxidant enzyme activity (Superoxide Dismutase, Glutathione Peroxidase, and catalase), NO metabolites (NOx: nitrites and nitrates), ferric reducing antioxidant power, Malondialdehyde (MDA), nitrotyrosine, and carbonyls were measured in plasma. At Post-, MDA, and carbonyls increased (p < 0.05) in the RSN group both at rest (+90.6%) and also acutely in response to RSA (+22.9%); but not in RSH. At Post-, in the RSH group, catalase increased (p < 0.05) both at rest (+44.7%) and in response to the RSA test (+66.3%). At Post-, SOD, and nitrotyrosine decreased after RSA and at rest, regardless of the group (p = 0.0012 and p = 0.0413, respectively). At Post-, NOx decreased after the RSA test, regardless of the group (p < 0.05). In conclusion, several weeks of RSH training limits the increase in oxidative stress markers both at rest and in response to RSA test. Moreover, such training downregulated SOD activity, possibly due to an overproduction of reactive oxygen species. These findings could constitute a paradigm shift with a better enzymatic adaptation after RSH concomitant with a distinct reactive oxygen species (ROS) production between RSH and RSN.

N-acetylneuraminic acid promotes ferroptosis of H9C2 cardiomyocytes with hypoxia/reoxygenation injury by inhibiting the Nrf2 axis.

To investigate the mechanism through which N-acetylneuraminic acid (Neu5Ac) exacerbates hypoxia/reoxygenation (H/R) injury in rat cardiomyocytes (H9C2 cells). H9C2 cells were cultured in hypoxia and glucose deprivation for 8 h followed by reoxygenation for different durations to determine the optimal reoxygenation time. Under the optimal H/R protocol, the cells were treated with 0, 5, 10, 20, 30, 40, 50, and 60 mmol/L Neu5Ac during reoxygenation to explore the optimal drug concentration. The cells were then subjected to H/R injury followed by treatment with Neu5Ac, Fer-1 (a ferroptosis inhibitor), or both. The changes in SOD activity, intracellular Fe2+ and lipid ROS levels in the cells were evaluated, and the cellular expressions of Nrf2, GPX4, HO-1, FSP1, and xCT proteins were detected using Western blotting. Following hypoxia and glucose deprivation for 8 h, the cells with reoxygenation for 6 h, as compared with other time lengths of reoxygenation except for 9 h, showed the lowest expression levels of Nrf2, GPX4, HO-1, and FSP1 proteins (P<0.001). Neu5Ac treatment of dose-dependently decreased the viability of the cells with H/R injury with an IC50 of 30.07 mmol/L. Reoxygenation for 3 h with normal glucose supplementation and a Neu5Ac concentration of 30 mmol/L were selected as the optimal conditions in the subsequent experiments. The results showed that Neu5Ac could significantly increase SOD activity, Fe2+ and lipid ROS levels and reduce Nrf2, GPX4, HO-1, and FSP1 protein expressions in H9C2 cells with H/R injury, but its effects were significantly attenuated by treatment with Fer-1. Neu5Ac exacerbates ferroptosis of myocardial cells with H/R injury by inhibiting the Nrf2 axis to promote the production of ROS and lipid ROS.

Hyperglycaemia-Induced Nephropathy is Prevented by Resveratrol and Pioglitazone Co-Administration in Type-2 Diabetic Male Wistar Rats

Background: Hyperglycaemia results in oxidative stress and activation of certain pathways such as that of aldose reductase, commonly observed in the development of diabetic nephropathy. The aim of this research was to evaluate the effect of resveratrol and pioglitazone co-administration in hyperglycaemia-induced nephropathy in type-2 diabetes. Methods: Thirty (30) adult male Wistar rats were induced with type-2 diabetes through high-fat-diet and fructose feeding for six weeks, followed by a single dose of 35 mg/kg streptozotocin (STZ) injection intraperitoneally. Rats with fasting blood glucose (FBG) levels of ≥ 200 mg/dL (20) were randomly divided into 5 groups of 4 rats each. Eight (8) other apparently healthy rats received regular diet and formed groups I and II of the experiment who received 1 ml/kg distilled water and 1 ml/kg carboxymethylcellulose (CMC) respectively, group III remained untreated, group IV, V, VI and VII received 100 mg/kg resveratrol, 5 mg/kg pioglitazone, 100 mg/kg resveratrol + 5 mg/kg pioglitazone and 1 mg/kg Lisinopril respectively. All interventions were given through oral route and lasted for six weeks post STZ injection. Rats were then fasted overnight and anaesthesized with 50 mg/kg ketamine hydrochloride and 25 mg/kg diazepam. Blood was collected via cardiac puncture in plain bottles and the right kidney of each rat was homogenized for biochemical assays. Data were analyzed and expressed as mean ± standard error of mean (SEM) using one way or repeated measure analysis of variance, followed by Tukey’s post-hoc test to compare level of significance, values of p ˂ 0.05 were considered statistically significant. Results: There was a significant decrease (p &lt; 0.05) in FBG levels between the co-administration and diabetic untreated groups at weeks 8, 10 and 12. Activities of antioxidant enzymes SOD, CAT and GSH in kidney homogenate increased significantly with a corresponding statistical significant decrease in MDA concentration between co-administration and diabetic untreated groups. Also, significant decreases (p&lt; 0.05) were seen in serum levels of aldose reductase and KIM-1 in the co-administration group compared to the diabetic control. Conclusion: The outcome of this study shows that resveratrol could potentially augment the effect of anti-diabetic drugs, in this case pioglitazone, in the prevention of diabetic nephropathy development in type-2 diabetes.

Isolation, Purification,andCharacterization of Lentinus edodes Polysaccharides Extracted with Subcritical Water Enhanced with Deep Eutectic Solvent.

TheLentinus edodespolysaccharide (LEP) was extracted witha new subcritical water extraction (SWE) enhanced with deep eutectic solvent (DES) methodand then purified with a DEAE-52 cellulose column and a Sephadex G-100 column. Two purifiedpolysaccharides (LEP1 and LEP2) were obtained and their structure, antioxidant activity,and immunomodulatory activitywere analyzed. LEP1 and LEP2 were composed ofmannose, glucose, and galactose with amolar ratio of 1:12.97:7.84 and 1:51.18:5.29, respectively. The molecular weightswere 9.878×104Da and 1.976×104Da, respectively. Interestingly, both LEP1 and LEP2 were mainly composed of→4)-β-D-Glcp-(1→, →6)-β-D-Glcp-(1→and →6)-α-D-Galp-(1→ withdifferentmolar ratio. Besides, both LEP1 and LEP2 hadstrong DPPH free radical scavenging activity and Fe2+ chelating capacity.Moreover, theycould reduce the level of ROS and regulate the activities of MDA, CAT, and SOD in HepG2 cells, demonstrating strong antioxidant activity. Furthermore, both LEP1 and LEP2 could improve the phagocytic capacity, NO release, and the content of IL-6, IL-1β,and TNF-α in RAW264.7 cells, exhibitedsignificant immunostimulatory activity. It wasworth noting that LEP2 exhibitedstronger biological activities than LEP1. Therefore, the SWE enhanced with DESis an ideal method for extracting polysaccharides, whichcan be further applied toextract otherpolysaccharides.

Association of -607C/A (rs1946518) and -137G/C (rs187238) polymorphisms and immune response in radiation-exposed workers

Purpose Interleukin-18, transforming growth factor-β, and superoxide dismutase are important cytokines and antioxidants in protecting the body from damage caused by radiation exposure through an immune response mechanism. Genetic polymorphisms −607 C/A and −137 G/C are thought to affect the IL-18 cytokine in carrying out its function as a biomarker to indicate adverse conditions due to radiation. The purposes of this study were to investigate the association between 607 C/A and −137 G/C SNPs on the concentrations of IL-18, and to measure TGF-β and SOD activity in radiation workers and control group. Material and method We enrolled 40 radiation workers and 40 non-radiation workers as a control group. We determined genotype distribution of −607 C/A and −137 G/C SNPs and their correlation with IL-18 concentration by using PCR-RFLP method. We also measured the IL-18, TGF-β concentration, and SOD activity by using Elisa assay. Results and conclusion No relationship was found between −607 C/A and −137 G/C on IL-18 concentrations in all genotype groups, and no significant difference in IL-18 and TGF-β concentrations in the radiation worker and control groups. Significant differences were found only in lower SOD activity in radiation workers compared to controls. The −607 C/A and −137 G/C did not significantly correlate with IL-18 cytokine production in all genotypes. There was no significant difference between IL-18 and TGF-β concentrations in the radiation worker and control groups. However, there was a very significant decrease in the SOD activity of the radiation workers by 3.31 times compared to the controls.

Thymelaea hirsuta extract attenuates testosterone-induced benign prostatic hyperplasia in rats: Effect on oxidative stress, inflammation and apoptosis.

Benign prostatic hyperplasia (BPH) is one of the most prominent diseases of the aged men urinary system. It is associated with cellular proliferation, hormonal imbalance, oxidative stress, inflammation and apoptosis. Traditionally, Thymelaea hirsuta (L.) (TH) leaves and flowers were used as a decoction or infusion in traditional medicine to treat skin disorders, urinary tract infection and infertility. To date, its potential protective effects for benign prostatic hyperplasia (BPH) have not been investigated. This study explored the effects of Thymelaea hirsuta extract (THE) on the development of BPH using a rat model of testosterone induced BPH. The THE phenolic composition was identified by liquid chromatography with a diode array detector (LC-DAD). Then, 21 male Wistar rats (Ten-week old) weighting 200-250g were separated into three groups: the group 1 was considered as a control while the group 2 and 3 received intramuscular injection of testosterone at dose of 3mg/kg (BPH). Only the group 3 received orally THE at dose of 36mg/kg. After four-week experimental time, the animals were sacrificed, and reproductive tissue was taken for histological and immunohistochemical analyses. Biochemical tests were also carried out. Additionally, the protein expression levels including in the inflammation pathway were analyzed by western blot. Our results revealed that THE treatment reduced the prostate weight and index. Orally THE administration improved the prostate biochemical and morphological characteristic in BPH rats and then lead to a normal prostate morphology restoration. As expected, THE supplementation significantly inhibited rat prostate enlargement, improved the pathological feature and reduced the epithelial thickness. Additionally, the anti-hyperplasic effect of THE is related to its possible ability to regulate the apoptotic and inflammatory pathways. Indeed, immunohistochemical and western blot analyses displayed a significant regulation of the apoptotic markers (Bax and Bcl-2) and a decrease in the inflammatory protein expression (NF-κB and TNF-α). Similarly, THE treatment increased the prostate cells' endogenous antioxidant capacity through the improvement of GSH level and the SOD activity. Conversely, it decreased the prostatic lipid peroxidation content. The HPLC-ESI-MSn analysis showed that chlorogenic acid and vicenin-2 were putatively identified as the major compounds of THE. The advanced results revealed the THE efficiency in the prevention of the testosterone-induced BPH in rats indicating that THE can be used as an alternative therapy for BPH management.

Effects of Astragaloside IV and Formononetin on Oxidative Stress and Mitochondrial Biogenesis in Hepatocytes.

Over-accumulation of reactive oxygen species (ROS) causes hepatocyte dysfunction and apoptosis that might lead to the progression of liver damage. Sirtuin-3 (SIRT3), the main NAD+-dependent deacetylase located in mitochondria, has a critical role in regulation of mitochondrial function and ROS production as well as in the mitochondrial antioxidant mechanism. This study explores the roles of astragaloside IV (AST-IV) and formononetin (FMR) in connection with SIRT3 for potential antioxidative effects. It was shown that the condition of combined pre- and post-treatment with AST-IV or FMR at all concentrations statistically increased and rescued cell proliferation. ROS levels were not affected by pre-or post-treatment individually with AST-IV or pre-treatment with FMR; however, post-treatment with FMR resulted in significant increases in ROS in all groups. Significant decreases in ROS levels were seen when pre- and post-treatment with AST-IV were combined at 5 and 10 μM, or FMR at 5 and 20 μM. In the condition of combined pre- and post-treatment with 10 μM AST-IV, there was a significant increase in SOD activity, and the transcriptional levels of Sod2, Cat, and GPX1 in all treatment groups, which is indicative of reactive oxygen species detoxification. Furthermore, AST-IV and FMR activated PGC-1α and AMPK as well as SIRT3 expression in AML12 hepatocytes exposed to t-BHP-induced oxidative stress, especially at high concentrations of FMR. This study presents a novel mechanism whereby AST-IV and FMR yield an antioxidant effect through induction of SIRT3 protein expression and activation of an antioxidant mechanism as well as mitochondrial biogenesis and mitochondrial content and potential. The findings suggest these agents can be used as SIRT3 modulators in treating oxidative-injury hepatocytes.

Acute Toxicity and Neuroprotective Effect of "RJ6601", a Newly Formulated Instant Soup, in Geriatric Rats.

Given its antioxidant effects and central nervous system benefits, we hypothesized that RJ6601 should improve neurodegeneration in the hippocampus, a region critical for cognition and the maintenance of quality of life (QoL). To assure its safety, a single fixed dose of 2000 mg/kg BW was administered to female Wistar rats (250-450 g, 18 months old) to test the acute toxicity of RJ6601. No mortality and toxicity signs were observed. To prove that RJ6601 can protect against age-related neurodegeneration, RJ6601 at doses of 200 and 400 mg/kg BW was administered to the female Wistar rats once daily for 4 weeks. At the end of the study period, assessments were conducted to evaluate the neuron density; MDA levels; and activities of SOD, CAT, GSH-Px, AChE, total MAO, MAO-A, and MAO-B in the hippocampus. Our results reveal increased neuron density, SOD, CAT, and GSH-Px but decreased MDA, AChE, total MAO, MAO-A, and MAO-B in the hippocampi of female Wistar rats subjected to RJ6601 treatment at both doses used in this study. Therefore, RJ6601 is considered to have low toxicity and may improve neurodegeneration as well as cholinergic and monoaminergic dysfunctions. Subchronic toxicity studies and clinical trials are essential to confirm the safety of RJ6601 consumption and its health benefits.

The Effect of Boric Acid on Oxidative Stress, Inflammation, and Apoptosis in Embryonic and Fetal Tissues Damage Caused by Consumption of High-Fructose Corn Syrup in Pregnant Rats.

This study aimed to determine the protective role of boric acid in a pregnant rat model of high fructose corn syrup consumption. Consumption of high fructose corn syrup has been associated with adverse health outcomes in humans and animals. Twenty-eight healthy female Wistar albino rats (250-300g weight and 16-24 weeks old) were randomly distributed into four equal groups (n = 7): Control, Boric acid (BA), High Fructose Corn Syrup (HFCS), HFCS + BA. Boric acid (20mg/kg) was administered to pregnant rats via oral gavage every day during pregnancy. The prepared 30% HFCS (F30) solution (24% fructose, 28% dextrose) was added to the drinking water throughout pregnancy. At the end of pregnancy (day 19), blood, placenta, uterus, and fetuses were collected from rats. The results indicated that HFCS increases oxidative stress by increasing the level of MDA and decreasing GSH, SOD, and CAT activity in the blood of maternal. However, BA administration significantly decreased MDA levels and increased GSH levels, SOD, and CAT activity (p < 0.05). In addition, HFCS consumption significantly increased plasma TNF-α, IL-6, and leptin levels compared to control, BA, and HFCS + BA groups (p < 0.05). However, BA administration significantly decreased plasma TNF-α, IL-6, and leptin levels (p < 0.05). Furthermore, BA (20mg/kg) significantly decreased HFCS-induced histopathological and immunohistochemical alterations in the placenta, uterus, and fetal tissue. In conclusion, BA may prevent HFCS toxicity in maternal and fetal tissues, as it regulates oxidative imbalance in pregnant rat and alleviates histopathological and immunohistochemical changes. The findings indicate a need for further studies to assess the potential of boron in preventing or mitigating the effects of HFCS during pregnancy.

Unraveling the Beneficial Role of Resveratrol in Fructose-Induced Non-Alcoholic Steatohepatitis with a Focus on the AMPK/Nrf2 Signaling Axis.

Background and Objectives: High fructose intake is associated with non-alcoholic fatty liver disease (NAFLD), a chronic liver disease that is on the rise worldwide. New alternatives for treatment, such as bioactive phytochemicals, are needed. The aim of this study was to investigate the beneficial role of resveratrol in treating non-alcoholic steatohepatitis (NASH). Materials and Methods: Sixty male albino rats were allocated to three groups: group I, the normal control group; group II, the fructose-enriched diet group (FED), which was fed a 70% fructose diet for six weeks to induce NASH; and group III, the resveratrol-FED group (RES + FED), which was given the same FED diet plus an oral dose of 70 mg/kg resveratrol (RES) every day for an additional six weeks. We performed histological evaluations and assessed blood lipids and liver enzymes to study resveratrol's impact on NASH. Quantitative real-time PCR was used to assess the mRNA expression of nuclear factor E2-related factor 2 (Nrf2) in the liver samples. ELISA was used to measure Beclin 1, AMPK, IL-6, and the DNA-binding activity of Nrf2. Oxidative stress indicators, including GSH, SOD, and MDA, were evaluated spectrophotometrically. Results: Resveratrol effectively alleviated the biochemical and histopathological abnormalities associated with NASH, improving autophagy by raising Beclin 1 levels while reducing inflammation by decreasing IL-6 levels. Furthermore, resveratrol restored the liver architecture and the oxidative balance, as evidenced by the decreased MDA levels and improved antioxidant status via elevated GSH and SOD activities, as well as the activation of the AMPK/Nrf2 signaling axis. Conclusions: This study specifically examines resveratrol's therapeutic effects in a high-fructose diet-induced NASH model, focusing on the AMPK/Nrf2 signaling pathway to address oxidative stress and autophagy, providing novel insights into its molecular mechanism of action. Resveratrol reduces NASH by boosting autophagy and activating the AMPK/Nrf2 pathway. These findings underscore the potential of resveratrol as a promising therapeutic agent that can support treatment alongside conventional medications in the management of non-alcoholic steatohepatitis (NASH).

Construction and analysis of the immune effect of subunit vaccines based on the flagellin FlaB and FlaC of Vibrioharveyi.

Vibrio harveyi is a common sort of pathogenic bacterium in marine, which annually gives rise to huge financial losses in aquaculture industry. Flagellin is one of the important virulence factors for bacteria, but meanwhile it is also a preferable vaccine candidate. In this study, we have identified and analyzed two flagellin antigens of V. harveyi, FlaB and FlaC; and moreover, on this basis, two subunit vaccines (rFlaB and rFlaC) were constructed, and the potential as vaccines against V. harveyi infection were determined and compared. Sequence analysis indicated that the coding region of FlaB was 1131 bp, sharing the highest sequence identity (97.07%) with the counterparts of V. campbellii, and that FlaC (1155 bp) shared the highest sequence identity (98.18%) with the counterparts of V. campbellii. The vaccine potential of subunit vaccines, rFlaB and rFlaC, were analyzed in the Epinephelus coioides model. The results showed that fish vaccinated with rFlaB or rFlaC at 4-week post-vaccination (p.v.), exhibiting a relative percent survival (RPS) of 81.8% and 59.1%, respectively; when fish were vaccinated with rFlaB or rFlaC at 8-week p.v., the RPS of rFlaB and rFlaC were 76.2% and 42.9%, respectively. Compared to control group, immunological analysis showed that both rFlaB and rFlaC could elicited specific antibody expression and innate immune responses. Of note, rFlaB could induce higher levels of IgM, AKP, LZM, ACP and SOD activity in fish in comparison with rFlaC. Additionally, qPCR results manifested that the expressions of IL-1β, CD4, CD8α, IgM, IFNγ, MHCⅠα, MHCⅡα, TLR5M and TLR5S were significantly up-regulated in the fish immunized with rFlaB and rFlaC, indicating their ability to activate innate immunity and trigger the inflammatory and cell immune responses. Overall, FlaB is superior to FlaC as regards potential as vaccines. This research has developed two promising subunit vaccines against diseases caused by V. harveyi that are well-suited for application in aquaculture.