Glutathione Peroxidase Research Articles

The effects of highly bioavailable curcumin in downhill running-induced muscle damage model

ABSTRACT Curcumin is a natural polyphenolic compound exerting antioxidative and anti-inflammatory effects on various tissues, including muscles. Nevertheless, its clinical usage has been limited because of its poor bioavailability. Thus, highly bioavailable curcumin, such as Theracurmin (CR-033P) composed of 36% crystalline curcumin, has been developed. This study investigated the antioxidant activity and muscle-protective effect of Theracurmin Super (TS-P1), a new formulation with 36% amorphous curcumin. TS-P1 and CR-033P demonstrated antioxidant activity in vitro. Compared with pure curcumin, orally administered TS-P1 or CR-033P (16.7 or 50 mg per kg of body weight) at one-third dose inhibited the elevation of plasma lactate dehydrogenase and creatine kinase levels in a mouse downhill running model, indicating superior muscle-protective effect. Particularly, TS-P1 showed better or equivalent effectiveness in restoring the activity of antioxidant enzymes including glutathione peroxidase and catalase, and in suppressing inflammatory responses. Therefore, formulation with amorphous curcumin is a promising strategy for curcumin-based supplements.

Decreased antioxidant capacity in children with diabetic ketoacidosis

Objective. To analyze the levels of antioxidant enzyme superoxide dismutase (SOD) and glutathione peroxidase (GP) against the background of diabetic ketoacidosis (DKA) in type 1 diabetes mellitus (DM) children and adolescents. Materials and methods. The study involved examination of 74 children: 50 DKA children (study group) and 24 relatively healthy children (control group). The study group children were divided into two subgroups: subgroup 1 included children with DKA against the background of type 1 DM onset (n=27), subgroup 2 consisted of children with DKA against the background of chronic type 1 DM (n=23). SOD and GP concentrations in blood plasma were determined in all children by enzyme immunoassay. The reliability between the data was estimated using the Mann-Whitney test, Kruskal-Wallis test and Spearman coefficient. Results. A significant decrease in SOD and GP in children with DKA was revealed as follows: 13130 [13005–18255] Pg/ml and 50.085 [42.02–70.325] Ng/ml, compared to controls: 16415 [13370–19935] Pg/ml and 84.695 [52.49–144.5] Ng/ml, respectively. Minimal SOD and GP were noted in patients with DKA at the background of chronic type 1 DM, compared to DM onset children. The study indicates a reliable correlation between age, duration of the disease, number of DKA in the history and low values of SOD and GP. Conclusion. Decreased antioxidant capacity was found in children with DKA in type 1 DM. SOD and GP can be considered in pediatric practice as markers of oxidative stress in DKA. In addition, an early detection of SOD and GP contributes to the efficient therapy of DKA in children and adolescents.

Cyclophosphamide induces ovarian granulosa cell ferroptosis via a mechanism associated with HO-1 and ROS-mediated mitochondrial dysfunction

Abnormal granulosa cell (GC) death contributes to cyclophosphamide (CTX) induced primary ovarian insufficiency (POI). To investigate the contribution of GCs to POI, gene profiles of GCs exposed to CTX were assessed using RNA-Seq and bioinformatics analysis. The results showed the differentially expressed genes (DEGs) were enriched in the ferroptosis-related pathway, which is correlated with upregulated heme oxygenase 1 (HO-1) and downregulated glutathione peroxidase-4 (GPX4). Using CTX-induced cell culture (COV434 and KGN cells), the levels of iron, reactive oxygen species (ROS), lipid peroxide, mitochondrial superoxide, mitochondrial morphology and mitochondrial membrane potential (MMP) were detected by DCFDA, MitoSOX, C11-BODIPY, MitoTracker, Nonylacridine Orange (NAO), JC-1 and transmission electron microscopy respectively. The results showed iron overload and disrupted ROS, including cytoROS, mtROS and lipROS homeostasis, were associated with upregulation of HO-1 and could induce ferroptosis via mitochondrial dysfunction in CTX-induced GCs. Moreover, HO-1 inhibition could suppress ferroptosis induced GPX4 depletion. This implies a role for ROS in CTX-induced ferroptosis and highlights the effect of HO-1 modulators in improving CTX-induced ovarian damage, which may provide a theoretical basis for preventing or restoring GC and ovarian function in patients with POI.

SELENOI Functions as a Key Modulator of Ferroptosis Pathway in Colitis and Colorectal Cancer.

Ferroptosis plays important roles both in normal physiology and multiple human diseases. It is well known that selenoprotein named glutathione peroxidase 4 (GPX4) is a crucial regulator for ferroptosis. However, it remains unknown whether other selenoproteins responsible for the regulation of ferroptosis, particularly in gut diseases. In this study, it is observed that Selenoprotein I (Selenoi) prevents ferroptosis by maintaining ether lipids homeostasis. Specific deletion of Selenoi in intestinal epithelial cells induced the occurrence of ferroptosis, leading to impaired intestinal regeneration and compromised colonic tumor growth. Mechanistically, Selenoi deficiency causes a remarkable decrease in ether-linked phosphatidylethanolamine (ePE) and a marked increase in ether-linked phosphatidylcholine (ePC). The imbalance of ePE and ePC results in the upregulation of phospholipase A2, group IIA (Pla2g2a) and group V (Pla2g5), as well as arachidonate-15-lipoxygenase (Alox15), which give rise to excessive lipid peroxidation. Knockdown of PLA2G2A, PLA2G5, or ALOX15 can reverse the ferroptosis phenotypes, suggesting that they are downstream effectors of SELENOI. Strikingly, GPX4 overexpression cannot rescue the ferroptosis phenotypes of SELENOI-knockdown cells, while SELENOI overexpression can partially rescue GPX4-knockdown-induced ferroptosis. It suggests that SELENOI prevents ferroptosis independent of GPX4. Taken together, these findings strongly support the notion that SELENOI functions as a novel suppressor of ferroptosis during colitis and colon tumorigenesis.

ARID3A enhances chemoresistance of pancreatic cancer via inhibiting PTEN-induced ferroptosis

Currently, chemotherapy remains occupying a pivotal place in the treatment of pancreatic ductal adenocarcinoma (PDAC). Nonetheless, the emergence of drug resistance in recent years has limited the clinical efficacy of chemotherapeutic agents, especially gemcitabine (GEM). Through bioinformatics analysis, AT-rich Interactive Domain-containing Protein 3A (ARID3A), one of transcription factors, is discovered to possibly participate in this progress. This study thoroughly investigates the potential role of ARID3A in the malignant progression and GEM chemoresistance of PDAC and explores the underlying mechanisms. The results indicate that ARID3A knockdown suppresses tumor development and enhances the sensitivity of PDAC cells to GEM in vitro and vivo. Mechanically, CUT&Tag profiling sequencing, RNA‐sequencing and functional studies demonstrates that decreased ARID3A expression alleviates the transcriptional inhibition of phosphatase and tensin homolog (PTEN), consequently leading to glutathione peroxidase 4 (GPX4) depletion and increased lipid peroxidation levels. Activated ferroptosis induced by the inhibition of GPX4 subsequently restricts tumor progression and reduces GEM resistance in PDAC. This research identifies the ferroptosis regulatory pathway of ARID3A-PTEN-GPX4 axis and reveals its critical role in driving the progression and chemoresistance of pancreatic cancer. Notably, both inhibition of ARID3A and enhancement of ferroptosis can increase chemosensitivity to GEM, which offers a promising opportunity for developing therapeutic strategies to combat acquired chemotherapy resistance in pancreatic cancer.

Prolactin is an Endogenous Antioxidant Factor in Astrocytes That Limits Oxidative Stress-Induced Astrocytic Cell Death via the STAT3/NRF2 Signaling Pathway

Oxidative stress-induced death of neurons and astrocytes contributes to the pathogenesis of numerous neurodegenerative diseases. While significant progress has been made in identifying neuroprotective molecules against neuronal oxidative damage, little is known about their counterparts for astrocytes. Prolactin (PRL), a hormone known to stimulate astroglial proliferation, viability, and cytokine expression, exhibits antioxidant effects in neurons. However, its role in protecting astrocytes from oxidative stress remains unexplored. Here, we investigated the effect of PRL against hydrogen peroxide (H2O2)-induced oxidative insult in primary cortical astrocyte cultures. Incubation of astrocytes with PRL led to increased enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX), resulting in higher total antioxidant capacity. Concomitantly, PRL prevented H2O2-induced cell death, reactive oxygen species accumulation, and protein and lipid oxidation. The protective effect of PRL upon H2O2-induced cell death can be explained by the activation of both signal transducer and activator of transcription 3 (STAT3) and NFE2 like bZIP transcription factor 2 (NRF2) transduction cascades. We demonstrated that PRL induced nuclear translocation and transcriptional upregulation of Nrf2, concurrently with the transcriptional upregulation of the NRF2-dependent genes heme oxygenase 1, Sod1, Sod2, and Gpx1. Pharmacological blockade of STAT3 suppressed PRL-induced transcriptional upregulation of Nrf2, Sod1 and Gpx1 mRNA, and SOD and GPX activities. Furthermore, genetic ablation of the PRL receptor increased astroglial susceptibility to H2O2-induced cell death and superoxide accumulation, while diminishing their intrinsic antioxidant capacity. Overall, these findings unveil PRL as a potent antioxidant hormone that protects astrocytes from oxidative insult, which may contribute to brain neuroprotection.

Biochar and silicon relegate the adversities of beryllium stress in pepper by modulating methylglyoxal detoxification and antioxidant defense mechanism.

Industrial activities have escalated beryllium (Be) release in environment which negatively affect plant growth and human health. This investigation describes Be-induced stress in pepper and its palliation by application of pineapple fruit peel biochar (BC) and potassium silicate (Si). The treatment of Be reduced seedling length, biomass, and physiological attributes and enhanced electrolyte leakage, hydrogen peroxide (H2O2), superoxide (O2•-) level in pepper plants; however, these oxidative stress markers were reduced with combined treatment (Be + BC + Si). Application of BC and Si also lowered Be cumulation in roots and shoots of pepper. Under combined treatment, superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) activities exhibited significant enhancement 19, 7.6, 22.8, and 48%, respectively, in Be-stressed pepper. The Be + BC + Si increased peroxidase (POD), glutathione S-transferase (GPX), and glutathione peroxidase (GST) activities 121, 55, and 53%, respectively, as compared to Be-treated pepper. Methylglyoxal level was reduced in pepper with rise in glyoxalase I and II enzymes. Thus, combined application of SS and BC effectively protects pepper against oxidative stress induced by Be by increasing both antioxidant defense and glyoxalase systems. Hence, pineapple fruit peel biochar along with potassium silicate can be used for enhancing crop productivity under Be-contaminated soil.

Efficacy of supplementing Aspergillus awamori in enhancing growth performance, gut microbiota, digestibility, immunity, and antioxidant activity of heat-stressed broiler chickens fed diets containing olive pulp

BackgroundGut microbes play a significant role in digestion, developing immunity, and intestinal health. Therefore, direct-fed microbials are used to modify gut microbiota, maintain a healthy digestive system, enhance immunity, and promote the broilers’ performance. In addition, it has a role in improving the utilization of unconventional feed ingredients (olive pulp, OP). This study provides the potential role of Aspergillus awamori in enhancing gut microbial content, nutrient utilization, growth performance, and antioxidative status in heat-stressed broiler chickens fed diets containing olive pulp.MethodsThree hundred chicks (Ross 308; one day old) were divided into four treatment groups (75 chick/ group) randomly, as follows; CON: chicks fed a basal diet based on corn and soybean meal, OP10: chicks fed a diet containing 10% OP, OA1: chicks fed a diet containing OP with A. awamori at 100 mg per kg, OA2: chicks fed a diet containing OP with A. awamori at 200 mg per kg.ResultsAdding A. awamori to the broiler diet that contains OP had a positive effect on productive performance via enhancing nutrition digestibility, body weight gain, feed conversion ratio, and carcass characteristics. A. awamori supplementation had a positive impact on immune responses by increasing serum immunoglobulin G and the relative weight of bursa of Fabricius (P < 0.05) compared to the other groups. Chickens fed A. awamori showed a noticeable improvement in the oxidative status through the increase in the level of serum superoxide dismutase, and glutathione peroxidase, and the decrease in the level of malondialdehyde. Feeding A. awamori also modified the intestinal microbial content by increasing the population of Lactobacillus (P < 0.05).ConclusionsOur study indicated that adding 200 mg A. awamori reduced the negative effect of heat stress by modifying the microbial content of the intestine, immune response, and enhancing feed utilization, thus improving broiler performance, as well as, improving the nutritional value of the olive pulp. Therefore, adding A. awamori to the OP diet can be effectively used in heat-stressed broiler diets.

Physiological and molecular responses of the copepods Acartia clausi and Acartia tonsa to nickel nanoparticles and nickel chloride

Nickel compounds in dissolved form or as nanoparticles may affect planktonic invertebrates in marine ecosystems. Here, we assessed the physiological (naupliar mortality, egg production, egg hatching success) and molecular (quantitative gene expression) responses of the crustacean copepods Acartia clausi (indigenous Mediterranean species) and Acartia tonsa (model organism in ecotoxicology), to nickel nanoparticles (NiNPs) and nickel chloride (NiCl2), over time. We also measured NPs size and the temporal release of Ni ions in aqueous solution, through dynamic light scattering (DLS) and inductively coupled plasma-mass spectrometry (ICP-MS), respectively.Nauplii of A. clausi were highly vulnerable to NiCl2 in the 48 h acute test, with an EC50 in the range of Ni concentrations measured in polluted waters. Females of both species exhibited a decreased egg production and hatching success after the 4-day exposure to NiNPs. Molecular responses in A. clausi incubated in NiNPs and NiCl2 showed a stronger up- or down-regulation, compared to A. tonsa, of genes associated with detoxification (phospholipid-hydroperoxide glutathione peroxidase, glutathione-S-transferase sigma), oxidative stress (superoxide dismutase), nervous system functioning (acetylcholinesterase), and oogenesis (vitellogenin).In conclusion, new information was here obtained on the effects of different forms of nickel on physiological and molecular responses of A. clausi, that could help to identify biomarker genes of exposure to be used as early-warning indicators. Our results also highlighted the need of employing indigenous copepod species to better evaluate the ecotoxicological impact of pollutants in different geographical area.

Effect of Scoparia dulcis Extract on Lipid Oxidation in Fish Feed, Growth Performance, and Hypoxia Tolerance in Juvenile Jian Carp (Cyprinus carpio var. Jian)

Lipid oxidation and hypoxia can lead to oxidative damage in aquatic animals. This study explored the effects of Scoparia dulcis extracts (SDE) on lipid oxidation, fish growth performance, digestive ability, antioxidant capacity, and hypoxia tolerance ability. The results showed that SDE decreased malonaldehyde (MDA), conjugated diene (CD), and peroxide value (PO) in the linoleic acid and linolenic acid as well as in fish feed. Broken-line analysis revealed that the optimal acetone extract of S. dulcis (AE) supplements was 4.02, 4.01, and 4.01 g kg−1 determined from PO, CD, and MDA, respectively. Dietary AE supplementation increased feed intake and specific growth rate and activities of amylase, trypsin, and lipase as well as alkaline phosphatase in fish hepatopancreas and gut. Polynomial regression analysis showed that optimal dietary AE supplement was 3.61 g kg−1 diet determined from weight gain. Furthermore, dietary AE supplementation decreased MDA content and increased glutathione content and the activities of glutathione peroxidase, catalase, superoxide dismutase, and glutathione reductase in fish digestive organs, gills, erythrocytes, and muscle. Dietary AE supplementation increased durative time (DT) and oxygen consumption rate (OCR) under hypoxia condition. Based on polynomial regression analysis, optimal dietary AE supplements were 4.73 and 4.60 g kg−1 diet determined from DT and OCR for hypoxia tolerance in fish, respectively. According to our current research, SDE’s antioxidant capacity may be attribute to their phenolic chemicals.

Selenium nanoparticles decorated with polysaccharides from Sargassum fusiforme protects against 6-OHDA-induced neurotoxicity in PC12 cells and rat model of Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder and identifying disease-causing pathways and drugs that target them has remained challenging. Herein, selenium nanoparticles decorated with polysaccharides from Sargassum fusiforme (SFPS-SeNPs) were investigated on 6-OHDA-induced neurotoxicity in PC12 cells and rats. 6-OHDA can significantly increase neurotoxicity, oxidative stress and decrease the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) both in vitro and vivo. In vitro, treatment with SFPS-SeNPs can significantly decrease 6-OHDA cytotoxicity, reactive oxygen species (ROS) production or malondialdehyde (MDA) levels, and cell apoptosis, significantly increased the activity of SOD and GPx. In vivo, 6-OHDA exposure could also decrease the expression of Nrf2 and OH-1, while treatment with SFPS-SeNPs (1 mg Se/kg) increased. SFPS-SeNPs can protect neurons from 6-OHDA-induced neurotoxicity by regulating apoptosis and Nrf2/ARE pathway. The present study demonstrated that SFPS-SeNPs is a good candidate for developing a new drug against neurodegenerative diseases such as PD.

Luteolin attenuates CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11.

Luteolin (3,4,5,7-tetrahydroxy flavone) is reported to strongly protect from acute carbon tetrachloride (CCl4) -induced liver injury or fibrosis. Ferroptosis can be induced by hepatic injury, and contributes to liver fibrosis development. The exact functional mechanism underlying luteolin inhibition of hepatic injury and whether ferroptosis is involved are unclear. Mice model and cell model of liver injury were constructed or induced to explore the effect and molecular mechanisms of Luteolin in the treatment of hepatic injury using CCl4. Cell Counting Kit-8 (CCK-8) and flow cytometry were used to evaluate HepG2 cell viability and apoptosis. The differential expressed genes involved in liver injury were scanned using RNA-seq and confirmed using functional study. Western blot was used to detect the indicators related to ferroptosis. Luteolin attenuated hepatic injury by alleviating cell morphology and decreasing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels in vivo mice models, and increasing cell viability, downregulating arachidonate 12-lipoxygenase (ALOX12), cyclooxygenase-2 (COX-2) and P21 protein expression, suppressing apoptosis in vitro cell models. Luteolin also inhibited ferroptosis by stimulating glutathione peroxidase 4 (GPX4) and mitochondrial ferritin (FTMT) protein expression, increasing glutathione (GSH) content, and minimizing Fe2+ and malondialdehyde (MDA) levels. Solute carrier family 7a member 11 (SLC7A11) was identified to be a key regulatory gene that participated in luteolin attenuation of CCl4-induced hepatic injuries in HepG2 cells using Microarray assay. Functional study showed that SLC7A11 can alleviate hepatic injury and ferroptosis. Luteolin attenuated CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11. SLC7A11 may serve as a novel alternative therapeutic target for hepatic injury.

Obesity aggravates neuroinflammatory and neurodegenerative effects of bisphenol A in female rats

Bisphenol A (BPA), a common plasticizer, is categorized as a neurotoxic compound. Its impact on individuals exhibits sex-linked variations. Several biological and environmental factors impact the degree of toxicity. Moreover, nutritional factors have profound influence on toxicity outcome. BPA has been demonstrated to be an obesogen. However, research on the potential role of obesity as a confounding factor in BPA toxicity is lacking. We studied the neurodegenerative effects in high-fat diet (HFD)-induced obese female rats after exposure to BPA (10 mg/L via drinking water for 90 days). Four groups were taken in this study – Control, HFD, HFD + BPA and BPA. Cognitive function was evaluated through novel object recognition (NOR) test. Inflammatory changes in brain, and changes in hormonal level, lipid profile, glucose tolerance, oxidative stress, and antioxidants were also determined. HFD + BPA group rats showed a significant decline in memory function in NOR test. The cerebral cortex (CC) of the brain showed increased neurodegenerative changes as measured by microtubule-associated protein-2 (MAP-2) accompanied by histopathological confirmation. The increased level of neuroinflammation was demonstrated by microglial activation (Iba-1) and protein expression of nuclear factor– kappa B (NF-КB) in the brain. Obesity also caused significant (p < 0.05) increase in lipid peroxidation accompanied by reduced activities of antioxidant enzymes (glutathione S-transferase, catalase and glutathione peroxidase) and decrease in reduced-glutathione (p < 0.05) when compared to non-obese rats with BPA treatment. Overall, study revealed that obesity serves as a risk factor in the toxicity of BPA which may exacerbate the progression of neurological diseases.

Potential use of antioxidants for the treatment of chronic inflammatory diseases.

The excessive production of various reactive oxidant species over endogenous antioxidant defense mechanisms leads to the development of a state of oxidative stress, with serious biological consequences. The consequences of oxidative stress depend on the balance between the generation of reactive oxidant species and the antioxidant defense and include oxidative damage of biomolecules, disruption of signal transduction, mutation, and cell apoptosis. Accumulating evidence suggests that oxidative stress is involved in the physiopathology of various debilitating illnesses associated with chronic inflammation, including cardiovascular diseases, diabetes, cancer, or neurodegenerative processes, that need continuous pharmacological treatment. Oxidative stress and chronic inflammation are tightly linked pathophysiological processes, one of which can be simply promoted by another. Although, many antioxidant trials have been unsuccessful (some of the trials showed either no effect or even harmful effects) in human patients as a preventive or curative measure, targeting oxidative stress remains an interesting therapeutic approach for the development of new agents to design novel anti-inflammatory drugs with a reliable safety profile. In this regard, several natural antioxidant compounds were explored as potential therapeutic options for the treatment of chronic inflammatory diseases. Several metalloenzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, are among the essential enzymes that maintain the low nanomolar physiological concentrations of superoxide (O2•-) and hydrogen peroxide (H2O2), the major redox signaling molecules, and thus play important roles in the alteration of the redox homeostasis. These enzymes have become a striking source of motivation to design catalytic drugs to enhance the action of these enzymes under pathological conditions related to chronic inflammation. This review is focused on several major representatives of natural and synthetic antioxidants as potential drug candidates for the treatment of chronic inflammatory diseases.

Ferrostatin-1 mitigates cellular damage in a ferroptosis-like environment in Caenorhabditis elegans.

Although iron (Fe) is the most biologically abundant transition metal, it is highly toxic when it accumulates as Fe2+, forming a labile Fe pool and favoring the Fenton reaction. This oxidative scenario leads to a type of caspase-independent programmed cell death, referred to as ferroptosis, where following processes take place: 1) Fe2+ overload; 2) glutathione peroxidase 4 inactivation; 3) lipid peroxidation and 4) glutathione depletion. The present study sought to evaluate the consequences of Fe2+ administration on ferroptosis induction in Caenorhabditis elegans. We demonstrated higher mortality, increased lipid peroxidation, reduced glutathione peroxidase activity, and morphological damage in dopaminergic neurons upon Fe2+ overload. Pharmacological intervention at the level of lipid peroxidation with ferrostatin-1 (250 μM) mitigated the damage and returned the biochemical parameters to basal levels, revealing the potential of this therapeutical approach. Finally, to assess the relationship between ferroptosis and dopamine in a Parkinsonian background, we evaluated the UA44 worm strain which overexpresses the alpha-synuclein protein in cherry-labeled dopaminergic neurons. We demonstrated that Fe2+ administration reduced lethality associated with similar alterations in biochemical and dopaminergic morphological parameters in wild-type animals. These experiments provide mechanistic-based evidence on the efficacy of a pharmacological approach to mitigate the physiological, biochemical, and morphological consequences of Fe2+ overload. At the same time, they encourage further research on the impact of the combined effects resulting from the genetic background and dopamine signaling in a Parkinsonian phenotype.

Apigenin intervenes in liver fibrosis by regulating PKM2-HIF-1α mediated oxidative stress

Apigenin (API) is a natural flavonoid compound with antioxidant, anti fibrotic, anti-inflammatory and other effects, but there is limited research on the effect of API on liver fibrosis. This study aims to explore the effect and potential mechanism of API on liver fibrosis induced by CCl4 in mice. The results indicate that API reduces oxidative stress levels, inhibits hepatic stellate cell (HSC) activation, and exerts anti liver fibrosis effects by regulating the PKM2-HIF-1α pathway. We observed that API alleviated liver tissue pathological damage and collagen deposition in CCl4 induced mouse liver fibrosis model, promoting the recovery of liver function in mice with liver fibrosis. In addition, the API inhibits the transition of Pyruvate kinase isozyme type M2 (PKM2) from dimer to tetramer formation by regulating the EGFR-MEK1/2-ERK1/2 pathway, thereby preventing dimer from entering the nucleus and blocking PKM2-HIF-1α access. This change leads to a decrease in malondialdehyde (MDA) and Catalase (CAT) levels and an increase in glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) levels, as well as total antioxidant capacity (T-AOC) in the liver of liver fibrosis mice. At the same time, API downregulated the expression of α-smooth muscle actin (α-SMA), Vimentin and Desmin in the liver tissue of mice with liver fibrosis, inhibited the activation of HSC, and reduced collagen deposition. These results indicate that API can inhibit HSC activation and alleviate CCl4 induced liver fibrosis by inhibiting the PKM2-HIF-1α pathway and reducing oxidative stress, laying an important foundation for the development and clinical application of API as a novel drug for treating liver fibrosis.

Association of Oxidative Stress on Cognitive Function: A Bidirectional Mendelian Randomisation Study.

The purpose of this study was to investigate the relationship between oxidative stress and cognitive function, encompassing cognitive performance, intelligence, memory, reaction time, speech and vision by a bidirectional Mendelian randomisation study. Independent genetic variants associated with glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), peroxiredoxin (PRDX), sulfhydryl oxidase (SOX) and thyroid peroxidase (TPO) were explored using a genome-wide association study (GWAS). The inverse variance weighted (IVW) or Wald ratio method was employed to ascertain the relationship between antioxidant enzymes and cognitive function. The MR analyses indicated that the MR effect estimates of GST (β = 0.0352, P = 0.0047, FDR = 0.0164) and TPO (β = 0.0531, P = 0.0003, FDR = 0.0021) were significantly associated with cognitive performance elevation. Furthermore, genetically predicted GST (β = 0.0334, P = 0.0043, FDR = 0.0151) and TPO (β = 0.0496, P = 0.0031, FDR = 0.0151) were found to be associated with high intelligence. Additionally, there were also some associations of SOX (β = 0.0243, P = 0.0283, FDR = 0.066) on high cognitive performance, TPO (β = 0.1189, P = 0.0315, FDR = 0.2205) on larger maximum digits remembered correctly, and SOX (β = - 0.2435, P = 0.0395, FDR = 0.1185) on reaction time. Nevertheless, the associations between antioxidant enzymes and speech and linguistic disorders, as well as visual disturbances, were not significant. We did not find reverse causation between antioxidant enzymes and cognitive function traits. This study provides evidence of potential causal relationships between oxidative stress and cognitive function.

Antioxidant and Anti-Inflammatory Properties of Hydrolyzed Royal Jelly Peptide in Human Dermal Fibroblasts: Implications for Skin Health and Care Applications.

Hydrolyzed royal jelly peptide (RJP) has garnered attention for its health-promoting functions. However, the potential applications of RJP in skincare have not been fully explored. In this study, we prepared RJP through the enzymatic hydrolysis of royal jelly protein with trypsin and investigated its antioxidant and anti-inflammatory properties on primary human dermal fibroblasts (HDFs). Our results demonstrate that RJP effectively inhibits oxidative damage induced by H2O2 and lipid peroxidation triggered by AAPH and t-BuOOH in HDFs. This effect may be attributed to the ability of RJP to enhance the level of glutathione and the activities of catalase and glutathione peroxidase 4, as well as its excellent iron chelating capacity. Furthermore, RJP modulates the NLRP3 inflammasome-mediated inflammatory response in HDFs, suppressing the mRNA expressions of NLRP3 and IL-1β in the primer stage induced by LPS and the release of mature IL-1β induced by ATP, monosodium urate, or nigericin in the activation stage. RJP also represses the expressions of COX2 and iNOS induced by LPS. Finally, we reveal that RJP exhibits superior antioxidant and anti-inflammatory properties over unhydrolyzed royal jelly protein. These findings suggest that RJP exerts protective effects on skin cells through antioxidative and anti-inflammatory mechanisms, indicating its promise for potential therapeutic avenues for managing oxidative stress and inflammation-related skin disorders.

Protective Effects of Tunisian Orange Co-Product Extract and Oleuropein-Hesperidin Combination on Bleomycin-Induced Pulmonary Fibrosis in Rats.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia that leads to acute lung damage, deterioration of lung function, and increased mortality risk. In this study, we investigated the effects of the orange coproduct extract (OCE) and the combination of pure hesperidin and oleuropein (HO) on an experimental model of pulmonary fibrosis induced by bleomycin (BLM) in Wistar rats. Rats were divided into six groups: the control group (G1), the BLM group (G2), three groups (G3, G4, G5) receiving a single dose of BLM combined with OCE extract at 100, 200, and 300 mg/kg, and group 6 (G6) receiving a single dose of BLM combined with HO: both pure major phenolic compounds of OCE (hesperidin at 50 mg/kg) and olive leaves (oleuropein at 2.5 mg/kg). Oxidative stress in lung tissues was investigated using catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) assays and the measurement of malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels. Treatment with OCE and HO normalized the disturbance in oxidative markers' levels and showed a significant reduction in fibrosis score with no renal or hepatic toxic effects. In conclusion, OCE and HO exhibit antifibrotic effects on a rat model of pulmonary fibrosis.

Study on Soil Selenium-Induced Copper Deficiency in Yudong Black Goats.

Due to the degradation of pasture and strict restrictions on grazing ranges in recent years, copper (Cu) deficiency in Yudong black goats has been occurring, mainly manifested as emaciation, anemia, loss of appetite and lack of spirit. To explore the main causes of Cu deficiency in Yudong black goats, 40 black goats (1 year old, 25.11 ± 0.52 kg) were selected for this experiment; among them, 20 Yudong black goats with Cu deficiency from the experimental pasture were used as the experimental group, and 20 healthy Yudong black goats from the control pasture were used as the control group. In the pre-experiment, the mineral contents of the soil, forage, blood, and liver of black goats in both groups were determined, and in formal experiments, blood hematological, biochemical, antioxidant, and hemorheological parameters were analyzed. An experiment on the treatment of Cu deficiency in black goats was also conducted. This study showed that selenium (Se) levels in the soil, forage, blood, and liver from the experimental group were significantly lower than those from the control group (p < 0.01). The content of sulfur (S) in the forage was considerably higher than that of the control group (p < 0.01). The contents of Cu in the blood and liver from the experimental group were significantly lower than that from the control group (p < 0.01), and the content of S was considerably higher than that from the control group (p < 0.01). The blood hematology of the experimental group was affected, as evidenced by a decrease in hemoglobin, hematocrit value, mean corpuscular volume and mean corpuscular hemoglobin. The immunity and antioxidant capacity of black goats in the experiment group were impaired to varying degrees, with significant decreases in ceruloplasmin, immunoglobulin M, immunoglobulin G, glutathione peroxidase, and superoxide dismutase, and substantial increases in malondialdehyde. In addition, the experimental group showed a decrease in blood viscosity as evidenced by the rise in high shear viscosity, low shear viscosity, erythrocyte rigidity index, erythrocyte aggregation index, and erythrocyte deformation index, and a decrease in plasma viscosity. In the treatment experiment, oral administration of copper sulfate solution was carried out on 10 black goats with Cu deficiency. All the Cu deficiency goats were cured, and the Cu content in their bodies rebounded. In summary, low Se soil caused an increase in S content in the forage, and Yudong black goats feeding on high S forage resulted in a decrease in Cu absorption, which led to a secondary Cu deficiency.