Oxidative Stress Enzyme Activities Research Articles

Investigating the inhibitory effects of carotenoids-fortified Helix aspersa slime on oxidative stress, collagenase and tyrosinase enzyme activities.

The investigations of snail slime and its possible biological activities have been performed recently. This study aimed to evaluate the properties of Helix aspersa snail slime (HAS), and carotenoids-fortified slime (HASC). Snails were fed with carrots for 10 days. Slime was collected and extracted using water. Saponins identification, antioxidant, collagenase, and tyrosinase enzyme inhibition activities, carotenoids, total phenols, and flavonoids content, were determined. UHPLC-MS/MS analysis was performed for phytochemical characterization. Saponins were detected in the HAS extract only. However, HASC was shown to contain a higher carotenoid content than HAS (29.51 ± 0.4 vs. 18.11 ± 0.2 μg/g). similarly, total phenolic and flavonoid content were higher for the the HASC extract compared to the HAS (182.3 ± 5.2 vs. 150.28 ± 3.3 mg/g equivalent to gallic acid), and (77.62 ± 1.2 vs. 14.19 ± 0.9 mg/g equivalent to quercetin). As expected, the HASC extract exhibited higher antioxidant activity compared to the HAS, using DPPH and the ABTS assays (IC50 = 7.75 ± 0.14 vs. 20.1 ± 0.4 μg/mL), and (IC50 = 7.6 ± 0.26 vs. 19.57 ± 1.4 μg/mL). UHPLC-MS/MS analysis revealed the presence of several phytocomponents of which, hexadecanoic acid and ascorbic acid, were observed in the HASC extract. Furthermore, HASC extract exhibited superior inhibitory activity compared to HAS against collagenase and tyrosinase enzymes (IC50 = 8.4 ± 1.19 vs. 15.3 ± 1.12 μg/mL) and (IC50 = 30.1 ± 0.91 vs. 35 ± 1.3 μg/mL). These findings highlight the potential of HASC as a valuable ingredient in various pharmaceutical applications, due to their content of various phenolic, antioxidants, carotenoids, hexadecanoic, and ascorbic acids. The latter is well known for its great cosmeceutical applications used for slowing the process of skin aging.

Impacts of Combining Steinernema carpocapsae and Bracon hebetor Parasitism on Galleria mellonella Larvae.

The greater wax moth, Galleria mellonella, is a significant pest in apiculture and a well-established model organism for immunological and ecotoxicological studies. This investigation explores the individual and combined effects of the ectoparasite Bracon hebetor (B.h.) and the entomopathogenic nematode Steinernema carpocapsae (S.c.) on G. mellonella larvae. We evaluated the activity of oxidative stress enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), malondialdehyde (MDA) levels, cytochrome P450 activity, cell viability using Annexin V-FITC, DNA damage via comet assay, and larval morphology through scanning electron microscopy (SEM). Control larvae exhibited higher GPx and GST activities compared to those treated with B.h., S.c., or the B.h. + S.c. combination. Conversely, MDA levels displayed the opposite trend. SOD activity was reduced in the B.h. and S.c. groups but significantly higher in the combined treatment. Cytochrome P450 activity increased in response to parasitism by B. hebetor. The Annexin V-FITC assay revealed decreased cell viability in parasitized groups (B.h. 79.4%, S.c. 77.3%, B.h. + S.c. 70.1%) compared to controls. DNA damage analysis demonstrated significant differences between groups, and SEM observations confirmed severe cuticle abnormalities or malformations in G. mellonella larvae. These findings highlight the complex interactions between B. hebetor, S. carpocapsae, and their host, G. mellonella. Additionally, they illuminate the intricate physiological responses triggered within the host larvae.

Early Life Stress Influences Oxidative Stress Enzyme Activities in Liver, Heart, Kidney, Suprarenal Glands, and Pancreas in Male and Female Rat Pups.

Early life stress (ELS) is a risk factor for the development of chronic diseases resulting from functional alterations of organs in the cardiorespiratory and renal systems. This work studied the changes in oxidative stress enzyme activities (EAs) of SOD, CAT, GPX, GR, GST, NOS, MDA, and FRAP in different organs (heart, liver, kidney, adrenal glands (AGs), and pancreas) of male and female Sprague-Dawley rat pups on postnatal day (PN) 15, immediately after basal and acute or chronic stress conditions were accomplished, as follows: basal control (BC; undisturbed maternal pups care), stress control (SC; 3 h maternal separation on PN15), basal maternal separation (BMS; daily 3 h maternal separation on PN 1-14), and stress maternal separation (SMS; daily 3 h maternal separation on PN 1-14 and 3 h maternal separation on PN15). Acute or long-term stress resulted in overall oxidative stress, increase in EA, and reduced antioxidant capacity in these organs. Some different response patterns, due to precedent SMS, were observed in specific organs, especially in the AGs. Acute stress exposure increases the EA, but chronic stress generates a response in the antioxidant system in some of the organs studied and is damped in response to a further challenge.

Relationships between pesticides, polychlorinated biphenyls, blood parameters and oxidative stress of white stork Ciconia ciconia chicks in Poland

The white stork Ciconia ciconia is a bird species located at the top of the trophic pyramid in grassland and wetland ecosystems. This charismatic species is susceptible to pesticides and their environmental residues. In 2016, we collected blood samples from 114 white stork chicks across Western and Southern Poland. Chicks were sexed by molecular analysis and aged by development pattern. We studied the relationship between the concentration of pesticides (beta-HCH, heptachlor, aldrin, endrin, 4.4′-DDD, 4.4′-DDE and 4.4′-DDT) and of PCB in the chicks’ blood with blood morphology and biochemistry parameters in the blood. The mean (± SD) values of concentrations of above detection level pesticides were: for (1) beta-HCH 4.139 ± 19.205; (2) 4.4′-DDE 9.254 ± 91.491 and additionally (3) PCB 16.135 ± 44.777 ppb. We found negative relationships between beta-HCH and oxidative stress enzyme activity in the blood, between beta-HCH and leukocyte concentration and between 4.4′-DDE and catalase activity. We also found a positive relationship between the concentration of pesticides in blood and the age of chicks. Interestingly, we found a higher concentration of PCB in the blood of male stork chicks than in female stork chicks. We provide more evidence that the presence of pesticides in the environment can be a strong stress factor, shaping the health status of birds.

Degradation ability of Trichoderma spp. in the presence of poly(butylene adipate-co-terephthalate) microparticles

Investigating the effects of microplastics remains a pertinent issue given the extensive biodiversity of exposed organisms, variations in the mechanisms of action among individual polymers, and their reliance on environmental conditions. Therefore, the objective of the study was to investigate some interactions of the popular biodegradable plastic poly(butylene adipate-co-terephthalate) (PBAT) on some aspects of the physiology of filamentous fungi Trichoderma spp., integral components of the soil microbiome known for promoting plant growth and aiding in pollution remediation. In the two Trichoderma strains examined, a positive influence on fungal growth was observed in the presence of microplastics (MPs). The capability to degrade MPs with the involvement of cytochrome P450 monooxygenases was confirmed through the detection of terephthalic acid (TPA) in postculture extractions. Additionally, inhibition of degradative activity in the presence of MPs was observed for metolachlor (MET) and 2,4-dichlorophenoxyacetic acid (2,4-D). Moreover, biodegradation pathways with the involvement several dechlorinated or hydroxylated metabolites were proposed for examined compunds. Concentration-dependent shifts in oxidative stress enzymes activity and slight modifications in phospholipid profiles were noted for the tested PBAT concentrations. In summary, this study enhances our understanding of PBAT's impact on the physiology of filamentous fungal and their degradative capacities important for mitigating environmental pollution by xenobiotics and plastics.

Antiepileptic and antioxidant effects of aqueous extract of Lippia multiflora Moldenke (Verbenaceae) on pilocarpine-induced seizures in Mus musculus Swiss mice

Epilepsy is a chronic neurological disorder that affects the central nervous system. Approximately 3% of the population at some point in their lives would be affected by epileptic disorders in the world, that is to say nearly 70 million people and therefore about 85% live in developing countries. The objective of this study is to determine the anticonvulsant effects of Lippia multiflora on the animal model of epileptogenesis induced by pilocarpine injection in mice during the acute phase. Mice were treated with different doses of the aqueous extract of L. multiflora or sodium valproate. The anticonvulsant effects were evaluated 24 after the injection of pilocarpine by referring to the Racine scale. Then a daily treatment was done for one week corresponding to the acute stage of the disease. Oxidative stress parameters were measured from brain samples taken on the last day of treatment. The injection of pilocarpine induced the Status epilepticus, which is translated by the appearance of convulsive seizures while the administration of different doses of the aqueous extract of L. multiflora led to a significant decrease of the seizures induced by pilocarpine in mice. In addition, L. multiflora extract restored endogenous levels of oxidative stress markers (MDA and NO) and increased the activity of oxidative stress enzymes (SOD, CAT and GSH). L. multiflora possesses anticonvulsant properties mediated by the involvement of GABAA receptors and antioxidants.

Enhancing functional buffalo yogurt: Improving physicochemical properties, biological activities, and shelf life using marjoram and geranium essential oils

The use of essential oils (EO) has attracted interest in the food industry because of their wide range of beneficial properties. In this study, a new functional yogurt was developed using 2 EO, marjoram and geranium, at 3 different concentrations (0.2%, 0.4%, and 0.6% vol/vol). The physicochemical properties, including syneresis, viscosity, pH, and chemical composition; bioactivities, including antioxidant activity, anticancer and antibacterial effects, total phenolic content (TPC), and total flavonoid content (TFC); and sensory characteristics of the developed yogurt were evaluated. The findings indicated that the yogurts fortified with 0.6% marjoram or geranium exhibited higher viscosity and lower syneresis compared with other treatments. The yogurt supplemented with 0.6% marjoram displayed significant antibacterial activity against Listeria monocytogenes, Staphylococcus aureus, Salmonella typhimurium, and Escherichia coli. In addition, the yogurt enriched with geranium and marjoram oils at a concentration of 0.6% had notably significant (P < 0.05) higher TFC levels compared with the control sample and other concentrations. In the same context, in terms of TPC, yogurt supplemented with 0.6% marjoram displayed significantly (P < 0.05) elevated levels in comparison to the other samples tested. Yogurt enriched with marjoram oil exhibited noteworthy antioxidant activity, followed by geranium oil, compared with the control samples. The yogurt supplemented with 0.6% marjoram demonstrated strong radical scavenging activity, and the yogurt fortified with 0.6% geranium showed higher anticancer activity against HepG2 human liver carcinoma cells and oxidative stress enzyme activities. Among the various concentrations of EO tested, the yogurts fortified with 0.6% marjoram or geranium EO exhibited the most favorable outcomes, followed by 0.4% marjoram or geranium. To summarize, geranium and marjoram EO can be used as a potential nutritious ingredient and as a natural preservative for milk and related products.

Exploring the Associations of Inflammatory and Oxidative Stress Biomarkers with Pancreatic Diseases: An Observational and Mendelian Randomisation Study.

Identifying biomarkers linked to pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) is crucial for early detection, treatment, and prevention. Methods: Association analyses of 10 serological biomarkers involved in cell signalling (IFN-γ, IL-6, IL-8, IL-10), oxidative stress (superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities, total glutathione (GSH), malondialdehyde (MDA) levels), and intestinal permeability proteins (zonulin, I-FABP2) were conducted across PDAC (n = 12), CP (n = 21) and control subjects (n = 23). A Mendelian randomisation (MR) approach was used to assess causality of the identified significant associations in two large genetic cohorts (FinnGen and UK Biobank). Results: Observational results showed a downregulation of SOD and GPx antioxidant enzyme activities in PDAC and CP patients, respectively, and higher MDA levels in CP patients. Logistic regression models revealed significant associations between CP and SOD activity (OR = 0.21, 95% CI [0.05, 0.89], per SD), GPx activity (OR = 0.28, 95% CI [0.10, 0.79], per SD), and MDA levels (OR = 2.05, 95% CI [1.36, 3.08], per SD). MR analyses, however, did not support causality. Conclusions: These findings would not support oxidative stress-related biomarkers as potential targets for pancreatic diseases prevention. Yet, further research is encouraged to assess their viability as non-invasive tools for early diagnosis, particularly in pre-diagnostic CP populations.

Consumption of Feed Supplemented with Oat Beta-Glucan as a Chemopreventive Agent against Colon Cancerogenesis in Rats

Colorectal cancer (CRC) accounts for 30% of all cancer cases worldwide and is the second leading cause of cancer-related deaths. CRC develops over a long period of time, and in the early stages, pathological changes can be mitigated through nutritional interventions using bioactive plant compounds. Our study aims to determine the effect of highly purified oat beta-glucan on an animal CRC model. The study was performed on forty-five male Sprague–Dawley rats with azoxymethane-induced early-stage CRC, which consumed feed containing 1% or 3% low molar mass oat beta-glucan (OBG) for 8 weeks. In the large intestine, morphological changes, CRC signaling pathway genes (RT-PCR), and proteins (Western blot, immunohistochemistry) expression were analyzed. Whole blood hematology and blood redox status were also performed. Results indicated that the histologically confirmed CRC condition led to a downregulation of the WNT/β-catenin pathway, along with alterations in oncogenic and tumor suppressor gene expression. However, OBG significantly modulated these effects, with the 3% OBG showing a more pronounced impact. Furthermore, CRC rats exhibited elevated levels of oxidative stress and antioxidant enzyme activity in the blood, along with decreased white blood cell and lymphocyte counts. Consumption of OBG at any dose normalized these parameters. The minimal effect of OBG in the physiological intestine and the high activity in the pathological condition suggest that OBG is both safe and effective in early-stage CRC.

Effect of brassinosteroids on rooting of the ornamental deciduous shrubs

Brassinosteroids are a developing group of growth regulators. They are a group of steroid hormones involved in plants’ physiological and developmental processes. Among other things, they are responsible for cell wall regeneration or cell elongation. This experiment aimed to examine the effect of rooting stimulants on rhizogenesis in cuttings of two deciduous shrub species: Philadelphus ’Virginal’ and Hydrangea paniculata ’Limelight’. Aqueous solutions of indole-3-butyric acid (IBA) at 200 mg·L–1, Brassinolide (BL) at 0.05% and 24-epibrassinolide (24epiBL) (0.05%) were used in this study. The results obtained showed that both auxin and both of the brassinosteroids used increased the percentage of rooted cuttings almost twice, the degree of rooted cuttings and root length – for BL + IBA – longer roots than the control by 41% in jasmine and by 59% in hydrangea. The growth regulators applied during the rooting of cuttings also caused changes in the organic compound content of plant tissues and the activity of oxidative stress enzymes. The studies and results suggest that brassinosteroids may soon replace the popular rooting stimulants.

Mechanism of composite passivators to reduce cadmium absorption and accumulation in Chinese cabbage on cadmium-polluted soil

Abstract Background The accumulation of heavy metals, including cadmium (Cd), in soil endangers the quality of agricultural products and can harm human health. At present, the application of passivators is a relatively efficient, quick, and economical way to address this problem. In the experimental site of the present study, the effects of different composite passivators (red mud + lime + phosphorite powder, red mud + lime + biochar, lime + humic acid + seafoam, seafoam + biochar + red mud, seafoam + biochar + phosphorite powder) on the physiology and biochemistry of Chinese cabbage were investigated. Results After passivator application, the soil’s effective state Cd content was reduced, and the Cd content, bioconcentration factor (BCF), transfer coefficient (TF), oxidative stress, and antioxidant enzyme activity levels of Chinese cabbage leaves and stalks were reduced to different degrees. The reduction of reactive oxygen species content was mainly owing to passivator application, which reduced the degree of oxidative stress and increased the content of osmotic substances, the activity of antioxidant enzymes, and the ability to scavenge hydroxyl radicals. The soluble protein content of Chinese cabbage was mainly increased by an increase in the content of osmotic substances and non-enzymatic antioxidant substances and a reduction in the inhibition of protein synthesis. Conclusions Our findings suggest that the reduction of reactive oxygen species was the main cause of the reduction of Cd accumulation, transport, and toxicity in leaves. The increase in soluble protein was the main cause of the reduction of Cd accumulation, transport, and toxicity in petioles. Graphical Abstract

Microbiome structure variation and soybean's defense responses during flooding stress and elevated CO2.

With current trends in global climate change, both flooding episodes and higher levels of CO2 have been key factors to impact plant growth and stress tolerance. Very little is known about how both factors can influence the microbiome diversity and function, especially in tolerant soybean cultivars. This work aims to (i) elucidate the impact of flooding stress and increased levels of CO2 on the plant defenses and (ii) understand the microbiome diversity during flooding stress and elevated CO2 (eCO2). We used next-generation sequencing and bioinformatic methods to show the impact of natural flooding and eCO2 on the microbiome architecture of soybean plants' below- (soil) and above-ground organs (root and shoot). We used high throughput rhizospheric extra-cellular enzymes and molecular analysis of plant defense-related genes to understand microbial diversity in plant responses during eCO2 and flooding. Results revealed that bacterial and fungal diversity was substantially higher in combined flooding and eCO2 treatments than in non-flooding control. Microbial diversity was soil>root>shoot in response to flooding and eCO2. We found that sole treatment of eCO2 and flooding had significant abundances of Chitinophaga, Clostridium, and Bacillus. Whereas the combination of flooding and eCO2 conditions showed a significant abundance of Trichoderma and Gibberella. Rhizospheric extra-cellular enzyme activities were significantly higher in eCO2 than flooding or its combination with eCO2. Plant defense responses were significantly regulated by the oxidative stress enzyme activities and gene expression of Elongation factor 1 and Alcohol dehydrogenase 2 in floodings and eCO2 treatments in soybean plant root or shoot parts. This work suggests that climatic-induced changes in eCO2 and submergence can reshape microbiome structure and host defenses, essential in plant breeding and developing stress-tolerant crops. This work can help in identifying core-microbiome species that are unique to flooding stress environments and increasing eCO2.

The effects of short-time air pollution, SO2, and ozone on biochemical, histo-pathological, oxidative stress, and carcinogenesis related genes expressions in the liver of the rats.

Air pollution is a universal issue and has significant deleterious effects on both human health and also environment. The important indicators of air pollution include ozone (O3), particulate matter (PM), nitrogen dioxide (NO2), and sulfur dioxide (SO2). This research aims to investigate the impacts of ambient air pollution (AAP), SO2, and O3 on oxidative stress parameters, liver tissue histopathology, and expression of some carcinogenesis-related genes in the hepatic tissue of rats. 32 Wistar rats were randomly allocated to four groups: the control group, the AAP group, the SO2 group (10 ppm), and the ozone group (0.6 ppm). Over a period of five consecutive weeks, the rats were exposed to the specified pollutants for 3 h daily; liver tissues were harvested and instantly fixed with formalin. Pathological changes were assessed in the tissue samples. Additionally, the RT-qPCR technique was utilized to investigate Expression alterations of BAX, p-53, BCL2, caspase-3, caspase-8 and caspase-9. Furthermore, 30 milligrams of hepatic tissues were extracted to assess the activities of oxidative stress enzymes. The liver catalase and MDA activity were elevated in the air pollution (p < .05). Also, liver GPx activity in air pollution and ozone groups was significant in comparison to the control group (p < .05). The SO2 group exhibited severe lesions in histopathology examinations. The findings revealed an alteration in liver histopathology, an induction of oxidative stress, and the expression of some apoptosis-related genes in hepatic tissues after exposure to AAP, SO2, and O3.

Effect of Irrigation With Household Detergent on Germination, Activities of Oxidative Stress Enzymes and Chlorophyll Content of Pod Maize

Effect of Irrigation With Household Detergent on Germination, Activities of Oxidative Stress Enzymes and Chlorophyll Content of Pod Maize

Effects of hypoxia stress on oxidative stress, apoptosis and microorganisms in the intestine of large yellow croaker (Larimichthys crocea)

In order to understand the physiological response of large yellow croaker under hypoxia stress, large yellow croaker with body weight of (31.67 ± 3.69) g was used as the research object. The 96 h hypoxia (2.0 ± 0.1) mg / L stress group and normoxia (7.8 ± 0.5) mg / L control group were set up. The changes of oxidative stress index, apoptosis rate, apoptosis-related gene expression, tissue morphology and microorganisms of large yellow croaker intestine in hypoxia stress group and normoxia control group were analyzed by biochemical detection, paraffin section, qRT-PCR and 16S rDNA sequencing. The results showed that the oxidative stress indexes such as ROS, SOD, CAT, MDA and GSH in the intestinal tissue of the hypoxic stress group were significantly higher than those in the control group. The expression of bax, caspase-3 and caspase-9 mRNA was significantly higher than that of the control group, and the expression of bcl2 mRNA was significantly lower than that of the control group. After 96 h of hypoxia stress, the apoptosis index of intestinal cells in in the hypoxia stress group was significantly higher than that in the control group, the number of intestinal goblet cells decreased, and the height, width of intestinal villi and muscle thickness were significantly lower than those in the control group. There were significant differences in intestinal microorganisms between the hypoxia stress group and the control group. The dominant bacteria involved in energy metabolism under hypoxia stress were Firmicutes and Bacteroidetes, and the dominant bacteria involved in intestinal inflammation were Proteobacteria. Oxidative stress enzyme activity and apoptosis gene expression were significantly correlated with the abundance changes of conditional pathogenic bacteria such as Mycoplasma, Staphylococcus and Pseudomonas, and beneficial bacteria such as Lactobacillus and Clostridium. The above results showed that hypoxia stress caused oxidative stress and apoptosis in large yellow croaker, and changed the intestinal tissue structure and intestinal microorganisms. Intestinal probiotics help fish to resist oxidative stress and apoptosis under hypoxic stress, while conditional pathogenic bacteria have the opposite effect. This study has accumulated basic biological data for the study of the physiological response mechanism of large yellow croaker to hypoxia stress, and provided new understanding for understanding the mechanism of hypoxia affecting fish intestinal health.

Liver metabolomics reveals potential mechanism of Jieduan-Niwan formula against acute-on-chronic liver failure (ACLF) by improving mitochondrial damage and TCA cycle

BackgroundAcute-on-chronic liver failure (ACLF) is a refractory disease with high mortality, which is characterized by a pathophysiological process of inflammation-related dysfunction of energy metabolism. Jieduan-Niwan formula (JDNWF) is a eutherapeutic Chinese medicine formula for ACLF. However, the intrinsic mechanism of its anti-ACLF effect still need to be studied systematically.PurposeThis study aimed to investigate the mechanism of JDNWF against ACLF based on altered substance metabolic profile in ACLF the expression levels of related molecules.Materials and methodsThe chemical characteristics of JDNWF were characterized using ultra performance liquid chromatography (UPLC) coupled with triple quadrupole mass spectrometry. Wistar rats subjected to a long-term CCL4 stimulation followed by a combination of an acute attack with LPS/D-GalN were used to establish the ACLF model. Liver metabolites were analyzed by LC–MS/MS and multivariate analysis. Liver function, coagulation function, histopathology, mitochondrial metabolic enzyme activity and mitochondrial damage markers were evaluated. The protein expression of mitochondrial quality control (MQC) was investigated by western blot.ResultsLiver function, coagulation function, inflammation, oxidative stress and mitochondrial enzyme activity were significantly improved by JDNWF. 108 metabolites are considered as biomarkers of JDNWF in treating ACLF, which were closely related to TCA cycle. It was further suggested that JDNWF alleviated mitochondrial damage and MQC may be potential mechanism of JDNWF improving mitochondrial function.ConclusionsMetabolomics revealed that TCA cycle was impaired in ACLF rats, and JDNWF had a regulatory effect on it. The potential mechanism may be improving the mitochondrial function through MQC pathway, thus restoring energy metabolism.

Phlorizin, a novel caloric restriction mimetic, stimulates hypoxia and protects cardiomyocytes through activating autophagy via modulating the Hif-1α/Bnip3 axis in sepsis-induced myocardial dysfunction

BackgroundSepsis is a systemic inflammatory syndrome that can lead to multiple organ dysfunction and life-threatening complications. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to be present in half of patients with septic shock, increasing their mortality rate to 70–90%. The pathogenesis of SIMD is complex, and no specific clinical treatment has yet been developed. Caloric restriction mimetics (CRM), compounds that simulate the biochemical and functional properties of CR, can improve cardiovascular injury by activating autophagy. This study investigated the effect of a new type of CRM which can induce hypoxia, the SGLT nonspecific inhibitor phlorizin on SIMD. Materials and methodsIn vivo, phlorizin was administered at 1 mg/kg/day intragastrically for 28 days. In vitro, AC16 was treated with 120 μM phlorizin for 48 h. Echocardiography was used to assess cardiac function. Myocardial injury markers were detected in serum and cell supernatant. Western blotting was employed to detect changed proteins associated with apoptosis and autophagy. Immunofluorescence, immunohistochemistry, co-immunoprecipitation, molecular docking, and other methods were also used to illustrate cellular changes. ResultsIn vivo, phlorizin significantly improved the survival rate and cardiac function after sepsis injury, reduced markers of myocardial injury, inhibited myocardial apoptosis and oxidative stress, and promoted autophagy. In vitro, phlorizin alleviated the apoptosis of AC16, as well as inhibited oxidative stress and apoptotic enzyme activity. Phlorizin acts on autophagy at multiple sites through low energy (activation of AMPK) and hypoxia (release of Beclin-1 by Hif-1α/Bnip3 axis), promoting the formation and degradation of autophagosomes. ConclusionWe indicated for the first time that phlorizin could inhibit glucose uptake via GLUT-1 and conforms to the metabolic characteristics of CRM, it can induce the hypoxic transcriptional paradigm. In addition, it inhibits apoptosis and improves SIMD by promoting autophagy generation and unobstructing autophagy flux. Moreover, it affects autophagy by releasing Beclin-1 through the Hif-1α/Bnip3 axis.

Duloxetine HCl Alleviates Asthma Symptoms by Regulating PI3K/AKT/mTOR and Nrf2/HO-1 Signaling Pathways.

Asthma is an inflammatory disease characterized by airway hyperresponsiveness, airway remodeling, and airway inflammation. In recent years, the prevalence of asthma has been increasing steadily and the pathogenesis of asthma varies from person to person. Due to poor compliance or resistance, existing drugs cannot achieve the desired therapeutic effect. Therefore, developing or screening asthma therapeutic drugs with high curative effects, low toxicity, and strong specificity is very urgent. Duloxetine HCl (DUX) is a selective serotonin and norepinephrine reuptake inhibitor, and it was mainly used to treat depression, osteoarthritis, and neuropathic pain. It was also reported that DUX has potential anti-infection, anti-inflammation, analgesic, antioxidative, and other pharmacological effects. However, whether DUX has some effects on asthma remains unknown. In order to investigate it, a series of ex vivo and in vivo experiments, including biological tension tests, patch clamp, histopathological analysis, lung function detection, oxidative stress enzyme activity detection, and molecular biology experiments, were designed in this study. We found that DUX can not only relax high potassium or ACh precontracted tracheal smooth muscle by regulating L-type voltage-dependent Ca2+ channel (L-VDCC) and nonselective cation channel (NSCC) ion channels but also alleviate asthma symptoms through anti-inflammatory and antioxidative response regulated by PI3K/AKT/mTOR and Nrf2/HO-1 signaling pathways. Our data suggests that DUX is expected to become a potential new drug for relieving or treating asthma.

Assessment of the Oxidative Stress Status in those with Diabetes and Hypertension Attending Jos University Teaching Hospital (JUTH), Nigeria

Diabetes is a serious, long-term condition with a major impact on the lives and wellbeing of individuals, families, and societies worldwide. This study aimed to investigate the impact of oxidative stress on individuals with type 2 diabetes mellitus (T2DM) and hypertension who were receiving care at the Endocrinology unit of Jos University Teaching Hospital (JUTH). A total of 54 subjects, comprising both males and females, were randomly selected for the study. The subjects included 27 patients diagnosed with T2DM and hypertension, as well as 27 healthy volunteers who were recruited as a control group. The study focused on assessing various parameters related to oxidative stress and antioxidant enzyme activity. The evaluation of oxidant status involved measuring Malondialdehyde (MDA) levels, which serve as a marker for lipid peroxidation, as well as Glycated hemoglobin (HbA1c) levels and Lipid profile. Additionally, the activity of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH), was examined. Demographic information, lifestyle factors, and clinical assessments were also collected during the study. The results showed that HbA1c levels were significantly higher in diabetic patients compared to the healthy participants. Furthermore, the diabetic group exhibited higher MDA activity, indicating increased lipid peroxidation, compared to the control group (P = 0.001). In terms of antioxidant enzyme activity, the diabetic group showed elevated levels of SOD, CAT, and GSH compared to the control group (P = 0.001). Regarding lifestyle factors, there was a significant difference (P = 0.001) in lipid profiles between diabetic and non-diabetic individuals who engaged in regular exercise compared to those who did not exercise. Similarly, diabetic individuals who had consultations with a registered dietician or an Endocrinologist also demonstrated significantly improved lipid profiles compared to those who did not seek professional advice. Notably, diabetics who exercised regularly and received dietary guidance exhibited significantly higher levels of HDL compared to those who did not engage in exercise or receive dietary counseling. In conclusion, this study highlighted the association between oxidative stress and T2DM with hypertension. The findings emphasized the importance of managing oxidative stress through lifestyle modifications, such as regular exercise and dietary interventions, in improving lipid profiles and potentially mitigating the impact of diabetes on individuals' health and well-being.

Withania somnifera inhibits photorefractoriness which triggers neuronal apoptosis in both pre-optic and paraventricular hypothalamic area of Coturnix coturnix japonica: involvement of oxidative stress induced p53 dependent Caspase-3 mediated low immunoreactivity of estrogen receptor alpha.

Light has a very important function in the regulation of the normal physiology including the neuroendocrine system, biological rhythms, cognitive behavior, etc. The variation in photoperiod acts as a stressor due to imbalance in endogenous hormones. Estrogen and its receptors ER alpha and beta play a vital role in the control of stress response in birds. The study investigates the estrogenic effects of a well-known medicinal plant Withania somnifera (WS), mediated by estrogen receptor alpha (ERα) in the hypothalamic pre-optic area (POA) and paraventricular nuclei (PVN). Further the study elucidates its anti-oxidants and anti-apoptotic activities in the brain of Japanese quail. To validate this hypothesis, mature male quails were exposed to long day length for 3months and then transferred to intermediate day length to become photorefractory (PR) while controls were still continued under long daylength. Supplementation of WS root extract in PR quail increases plasma estrogen and lowers corticosterone. Further, in PR quail the variation in light downregulates immunoreactivity of ERα, oxidative stress and antioxidant enzyme activities i.e. superoxide dismutase and catalase in the brain. Neuronal apoptosis was observed in the POA and PVN of PR quail as indicated by the abundant expression of Caspase-3 and p53 which reduces after the administration of WS root extract. The neuronal population also found to decrease in PR although it increased in WS administered quails. Further, the study concluded that change in photoperiod from 3months exposure of 16L: 8D to 13.5L: 10.5D directly activates neuronal apoptosis via expression of Caspase3 and p53 expression in the brain and increases neuronal and gonadal oxidative stress while WS root extract reverses them via enhanced estrogen and its receptor ERα expression in the hypothalamic pre-optic and PVN area of Japanese quail.