Endogenous Antioxidant Defense System Research Articles

The rhizobacterial Priestia megaterium strain SH-19 mitigates the hazardous effects of heat stress via an endogenous secondary metabolite elucidation network and molecular regulation signalling

Global warming is a leading environmental stress that reduces plant productivity worldwide. Several beneficial microorganisms reduce stress; however, the mechanism by which plant–microbe interactions occur and reduce stress remains to be fully elucidated. The aim of the present study was to elucidate the mutualistic interaction between the plant growth-promoting rhizobacterial strain SH-19 and soybeans of the Pungsannamul variety. The results showed that SH-19 possessed several plant growth-promoting traits, such as the production of indole-3-acetic acid, siderophore, and exopolysaccharide, and had the capacity for phosphate solubilisation. The heat tolerance assay showed that SH-19 could withstand temperatures up to 45 °C. The strain SH-19 was identified as P. megaterium using the 16S ribosomal DNA gene sequence technique. Inoculation of soybeans with SH-19 improved seedling characteristics under high-temperature stress. This may be due to an increase in the endogenous salicylic acid level and a decrease in the abscisic acid level compared with the negative control group. The strain of SH-19 increased the activity of the endogenous antioxidant defense system, resulting in the upregulation of GSH (44.8%), SOD (23.1%), APX (11%), and CAT (52.6%). Furthermore, this study involved the transcription factors GmHSP, GmbZIP1, and GmNCED3. The findings showed upregulation of the two transcription factors GmbZIP1 (17%), GmNCED3 (15%) involved in ABA biosynthesis and induced stomatal regulation, similarly, a downregulation of the expression pattern of GmHSP by 25% was observed. Overall, the results of this study indicate that the strain SH-19 promotes plant growth, reduces high-temperature stress, and improves physiological parameters by regulating endogenous phytohormones, the antioxidant defense system, and genetic expression. The isolated strain (SH-19) could be commercialized as a biofertilizer.

Muscle-derived IL-1β regulates EcSOD expression via the NBR1-p62-Nrf2 pathway in muscle during cancer cachexia.

Oxidative stress contributes to the loss of skeletal muscle mass and function in cancer cachexia. However, this outcome may be mitigated by an improved endogenous antioxidant defence system. Here, using the well-established oxidative stress-inducing muscle atrophy model of Lewis lung carcinoma (LLC) in 13-week-old male C57BL/6J mice, we demonstrate that extracellular superoxide dismutase (EcSOD) levels increase in the cachexia-prone extensor digitorum longus muscle. LLC transplantation significantly increased interleukin-1β (IL-1β) expression and release from extensor digitorum longus muscle fibres. Moreover, IL-1β treatment of C2C12 myotubes increased NBR1, p62 phosphorylation at Ser351, Nrf2 nuclear translocation and EcSOD protein expression. Additional studies in vivo indicated that intramuscular IL-1β injection is sufficient to stimulate EcSOD expression, which is prevented by muscle-specific knockout of p62 and Nrf2 (i.e. in p62 skmKO and Nrf2 skmKO mice, respectively). Finally, since an increase in circulating IL-1β may lead to unwanted outcomes, we demonstrate that targeting this pathway at p62 is sufficient to drive muscle EcSOD expression in an Nrf2-dependent manner. In summary, cancer cachexia increases EcSOD expression in extensor digitorum longus muscle via muscle-derived IL-1β-induced upregulation of p62 phosphorylation and Nrf2 activation. These findings provide further mechanistic evidence for the therapeutic potential of p62 and Nrf2 to mitigate cancer cachexia-induced muscle atrophy. KEY POINTS: Oxidative stress plays an important role in muscle atrophy during cancer cachexia. EcSOD, which mitigates muscle loss during oxidative stress, is upregulated in 13-week-old male C57BL/6J mice of extensor digitorum longus muscles during cancer cachexia. Using mouse and cellular models, we demonstrate that cancer cachexia promotes muscle EcSOD protein expression via muscle-derived IL-1β-dependent stimulation of the NBR1-p62-Nrf2 signalling pathway. These results provide further evidence for the potential therapeutic targeting of the NBR1-p62-Nrf2 signalling pathway downstream of IL-1β to mitigate cancer cachexia-induced muscle atrophy.

Magnesium, selenium and zinc deficiency compromises antioxidant defense in women with obesity.

Studies have shown that deficiencies in magnesium, selenium, and zinc in individuals with obesity compromise the endogenous antioxidant defense system. This study aimed to evaluate the impact of mineral deficiency on enzymatic antioxidant defense in women with obesity. The study involved 63 women with obesity (BMI ≥ 35kg/m2) and 77 eutrophic women (BMI between 18.5 and 24.9kg/m2). Variables such as fasting glucose, glycated hemoglobin, fasting insulin, and serum lipids were analyzed. Insulin resistance was measured using the homeostasis assessment model (HOMA-IR) and beta cell function using the homeostasis assessment model (HOMA-β). Dietary intake of energy, macronutrients (including magnesium, zinc, and selenium), and plasma, erythrocyte, and urinary concentrations of these minerals were measured and analyzed. Serum cortisol, plasma leptin, plasma thiobarbituric acid reactive substances, and the activity of erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPX), and erythrocyte catalase were also analyzed. Women with obesity had reduced plasma and erythrocyte concentrations and greater urinary excretion of all minerals compared to normal weight women (p < 0.05). There was a positive association between erythrocyte concentrations of zinc and selenium and the activity of the GPX and SOD enzymes in erythrocytes in women with obesity (p < 0.05), in addition to a positive association between serum insulin and the enzyme GPX, which is dependent on dietary selenium (p < 0.05). Individuals with obesity are deficient in magnesium, selenium, and zinc, which appears to impair the antioxidant defense system and contribute to important metabolic disorders such as oxidative stress in these patients.

Oxidative Stress and Dopaminergic Metabolism: A Major PD Pathogenic Mechanism and Basis of Potential Antioxidant Therapies

Reactive oxygen species (ROS)-induced oxidative stress triggers the vicious cycle leading to the degeneration of dopaminergic neurons in the nigra pars compacta. ROS produced during the metabolism of dopamine is immediately neutralized by the endogenous antioxidant defense system (EADS) under physiological conditions. Aging decreases the vigilance of EADS and makes the dopaminergic neurons more vulnerable to oxidative stress. As a result, ROS left over by EADS oxidize the dopamine-derived catechols and produces a number of reactive dopamine quinones, which are precursors to endogenous neurotoxins. In addition, ROS causes lipid peroxidation, uncoupling of the electron transport chain, and DNA damage, which lead to mitochondrial dysfunction, lysosomal dysfunction, and synaptic dysfunction. The mutations in genes such as DNAJC6, SYNJ1, SH3GL2, LRRK2, PRKN, and VPS35 caused by ROS have been associated with synaptic dysfunction and the pathogenesis of Parkinson’s disease (PD). The available drugs that are used against PD can only delay the progression of the disease, but they produce various side effects. Through their antioxidant activity, flavonoids can substantiate the EADS of dopaminergic neurons and disrupt the vicious cycle incepted by oxidative stress. In this review, we show how the oxidative metabolism of dopamine generates ROS and dopamine-quinones, which then exert unrestrained OS, causing mutations in several genes involved in the proper functioning of mitochondrion, synapse, and lysosome. Besides, we also present some examples of approved drugs used for the treatment of PD, therapies in the clinical trial phase, and an update on the flavonoids that have been tested to boost the EADS of dopaminergic neurons.

MnO2-coated nanodiamond-driven photodynamic therapy for enhanced antitumor effect by addressing hypoxia and glutathione depletion

The generation of reactive oxygen species (ROS) at the tumor site to induce destruction is emerging as a novel strategy for cancer treatment, which involves photodynamic therapy (PDT). Nevertheless, tumors typically create a hypoxic environment and are equipped with an endogenous antioxidant defense system that could potentially impede the efficiency of the therapeutic approach. To overcome these drawbacks, herein, a tumor microenvironment-responsive the ND-PAA-CD-Ce6@MnO2 (NPCC@M) delivery system was fabricated by disulfide bond coupling chlorin e6 (Ce6) to nanodiamond (ND) and further wrapped by MnO2 nanosheets to facilitate PDT. The use of disulfide bond not only stabilizes Ce6 in the blood circulation to prevent premature leakage, but also destroys the antioxidant barrier of overexpressed glutathione (GSH) in tumor cells. Moreover, the outer MnO2 was rapidly degraded by the endogenous hydrogen peroxide (H2O2) in the acidic pH and GSH within the tumor cells, which leads to an abundance of O2 and while increases the level of 1O2 under laser irradiation. The results eventually broke the redox homeostasis and attenuate hypoxia, thereby inducing apoptosis and necrosis of tumor cells. Detailed in vitro and in vivo biological effect has revealed a good biosafety profile and a high tumor suppression effect. Such a novel ND-based system with tumor microenvironment-modulating capability to elevate oxygen content and promote GSH consumption in tumor cells opens new opportunities for enhanced ROS treatment paradigms.

Chondrocyte-targeted exosome-mediated delivery of Nrf2 alleviates cartilaginous endplate degeneration by modulating mitochondrial fission

BackgroundCartilaginous endplate (CEP) degeneration, which is an important contributor to intervertebral disc degeneration (IVDD), is characterized by chondrocyte death. Accumulating evidence has revealed that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and dysfunction lead to apoptosis during CEP degeneration and IVDD. Exosomes are promising agents for the treatment of many diseases, including osteoporosis, osteosarcoma, osteoarthritis and IVDD. Despite their major success in drug delivery, the full potential of exosomes remains untapped.Materials and methodsIn vitro and in vivo models of CEP degeneration were established by using lipopolysaccharide (LPS). We designed genetically engineered exosomes (CAP-Nrf2-Exos) expressing chondrocyte-affinity peptide (CAP) on the surface and carrying the antioxidant transcription factor nuclear factor E2-related factor 2 (Nrf2). The affinity between CAP-Nrf2-Exos and CEP was evaluated by in vitro internalization assays and in vivo imaging assays. qRT‒PCR, Western blotting and immunofluorescence assays were performed to examine the expression level of Nrf2 and the subcellular localization of Nrf2 and Drp1. Mitochondrial function was measured by the JC-1 probe and MitoSOX Red. Mitochondrial morphology was visualized by MitoTracker staining and transmission electron microscopy (TEM). After subendplate injection of the engineered exosomes, the degree of CEP degeneration and IVDD was validated radiologically and histologically.ResultsWe found that the cargo delivery efficiency of exosomes after cargo packaging was increased by surface modification. CAP-Nrf2-Exos facilitated chondrocyte-targeted delivery of Nrf2 and activated the endogenous antioxidant defence system in CEP cells. The engineered exosomes inhibited Drp1 S616 phosphorylation and mitochondrial translocation, thereby preventing mitochondrial fragmentation and dysfunction. LPS-induced CEP cell apoptosis was alleviated by CAP-Nrf2-Exo treatment. In a rat model of CEP degeneration, the engineered exosomes successfully attenuated CEP degeneration and IVDD and exhibited better repair capacity than natural exosomes.ConclusionCollectively, our findings showed that exosome-mediated chondrocyte-targeted delivery of Nrf2 was an effective strategy for treating CEP degeneration.Graphic abstract CAP-Nrf2-Exos delivered Nrf2 into CEP cells and alleviated LPS-induced apoptosis by inhibiting Drp1-mediated mitochondrial fission

S-Nitrosoglutathione Attenuates Oxidative Stress and Improves Retention Memory Dysfunctions in Intra-Cerebroventricular-Streptozotocin Rat Model of Sporadic Alzheimer’s Disease via Activation of BDNF and Nuclear Factor Erythroid 2-Related Factor-2 Antioxidant Signaling Pathway

Plain Language SummaryThis work is mainly focused on the investigation of the antioxidant activity of S-nitrosoglutathione (GSNO) in intracerebroventricular infusion of streptozotocin (ICV-STZ)-induced Alzheimer’s disease (AD) in rats. GSNO is an endogenous nitric oxide donor and has potent antioxidant activities. Our study revealed for the first time that GSNO may have antioxidant activities in AD by improving the endogenous antioxidant defense system. Further, GSNO treatment improved spatial retention and contextual fear memory in rats. Also, GSNO treatment decreased the AD neuropathological parameters (neuronal damage, amyloid beta-Aβ40, Aβ42) and improved the neuroprotective parameters (GSH, brain-derived neurotrophic factor, and nuclear factor erythroid 2-related factor-2) levels in AD brain tissues. These findings indicate that GSNO activates the neuronal antioxidant defense system and normalizes oxidative stress in the AD brain.

Ginseng fruit rare saponins (GFRS), a promising anti-wrinkle agent: Evidence of its antioxidant effect and its capacity to prevent matrix metalloproteinase (MMPs) expression in vitro and in vivo

Rare saponins show numerous significant biological activities, however, there has been no research on using ginseng fruit rare saponins (GFRS) to minimize skin wrinkles. This paper studied the anti-wrinkle effect, related mechanism, material basis of efficacy, and structure-activity relationship of GFRS in vivo and in vitro. The findings demonstrate that GFRS has potent collagenase and elastase inhibition capabilities in addition to superior ultraviolet absorption properties. Secondly, GFRS can strengthen the endogenous antioxidant defense system, thus lessening the UVB-induced ultraviolet damage that L929 cells and zebrafish experience. Matrix metalloproteinases (MMPs) studies have shown that GFRS could significantly inhibit the UVB-induced MMP1 and MMP9 proteins production. Finally, the main ginsenoside component in GFRS was identified by LC-MS, and 16 kinds of ginsenoside were analyzed, including rare ginsenoside such as Rg6, F4, and R/S-Rg3, which may be caused by the transformation of prototype saponins Re and Rd caused by citric acid heat treatment (CAHT). After doing a quantitative HPLC analysis on twelve of them, it was discovered that CAHT could enrich the content of rare saponins in GFS. By evaluating these ginsenoside’s anti-wrinkle properties. It is found that the main material basis for GFRS’s anti-wrinkle action may be ginsenoside Rg6 or F4. In summary, GFRS exhibits promising properties as an anti-wrinkle treatment because of its robust anti-oxidation, anti-collagenase, anti-elastase activity, favorable ultraviolet absorption effect, and capacity to regulate MMPs in vivo and in vitro models.

Changes in Endogenous Intoxication and Antioxidant Defense System Markers in Patients with Tumor-Induced Acute Colonic Obstruction

A comprehensive evaluation of clinical and biochemical markers defining the status of endotoxemia in patients diagnosed with acute colonic obstruction (ACO) was conducted. The findings revealed that advancing stages of ACO corresponded to an increase in serum levels of endogenous intoxication markers and a simultaneous decrease in antioxidant defense system (ADS) markers.&#x0D; The aim of the study was to analyze changes in endogenous intoxication and ADS markers in patients with tumor-induced ACO throughout the disease progression and evaluate the outcomes.&#x0D; Materials and Methods. The study is based on examining serum levels of endogenous intoxication markers, including middle weight molecules (MWM), products of lipid peroxidation (LPO) - conjugated dienes (CD), malonaldehyde (MA), protein oxidative modification (POM), and key ADS markers, specifically superoxide dismutase (SOD), catalase (CAT), and ceruloplasmin (CP), in 155 patients with ACO throughout the disease progression and 20 apparently healthy individuals.&#x0D; Results. Upon patient admission to the hospital, the duration of ACO was found to correlate with an increase in endogenous intoxication markers and a decrease in antioxidant defense markers. Depending on ACO stage, MWM levels were 0.42 (0.38; 0.43) IU, 0.56 (0.51; 0.58) IU, and 0.72 (0.69; 0.73) IU, respectively (р1&lt;0.01, р2&lt;0.01, р3&lt;0.01), with a normal range of 0.23 (0.18; 0.25) IU. In the compensated stage of ACO, MA levels significantly increased compared to the control group, reaching 6.39 (6.25; 6.42) nmol/mL (р1&lt;0.001, р2&lt;0.01, р3&lt;0.05). Additionally, with the progression of the disease, a gradual increase in MA levels up to 6.39 (6.25; 6.42) nmol/mL, 7.88 (7.62; 7.92) nmol/mL, and 8.11 (8.05; 8.15) nmol/mL, respectively, was noted (р1&lt;0.001, р2&lt;0.01, р3&lt;0.05), with a normal range of 3.14 (2.58; 3.17) nmol/mL. Similar trend was observed in serum CD levels - 3.11 (3.02; 3.18) IU, 3.69 (3.52; 3.72) IU, and 4.69 (4.53; 4.82) IU, respectively, with a normal range of 1.41 (1.32; 1.46) IU (р1&lt;0.01, р2&lt;0.01, р3&lt;0.01). The study of LPO intensity via the optical density of aldehyde and ketone derivatives of neutral and basic dinitrophenylhydrazones (POM 356, POM 370, POM 430, POM 530) revealed an increase in POM product levels with the disease progression compared to the control group (р1&lt;0.001, р2&lt;0.01, р3&lt;0.01). The analysis of the ADS showed an opposite trend, characterized by a significant decrease in marker levels. In patients with different ACO stages, serum CAT levels were 8.08 (7.95; 8.12) Н2О2/mL, 6.32 (6.25;6.41) Н2О2/mL, and 5.67 (5.59; 5.75) Н2О2/mL, respectively, with a normal range of 12.36 (12.21; 12.55) Н2О2/ml (р1&lt;0.001, р2&lt;0.01, р3&lt;0.01), while SOD concentration decreased with the disease progression as well - 42.43 (31.75; 51.84) IU, 35.65 (24.72; 45.53) IU, and 32.18 (18.72; 41.15) IU, respectively, with a normal range of 63.60 (54.41; 74.56) IU (р1&lt;0.001, р2&lt;0.01, р3&lt;0.01). In the compensated stage of ACO, CP level exceeded the normal value - 39.21 (38.92; 39.41) IU, with a normal range of 28.9 (28.4; 29.1) IU, indicating a compensatory defensive response of the body to a dramatic increase in LPO products. CP reserves, however, were depleted with the disease progression and a consistent decrease in this marker was subsequently observed: 19.10 (18.91; 19.23) IU in the subcompensated stage and 16.12 (16.01; 16.15) IU in the decompensated stage (р1&lt;0.001, р2&lt;0.01, р3&lt;0.01).&#x0D; Conclusions. As a systemic process that induces various metabolic homeostasis disorders, endogenous intoxication serves as the pathogenetic foundation for the development of multiple organ failure in ACO patients. With ACO progression, endogenous intoxication caused an increase in LPO and POM activity, resulting in elevation of highly toxic middle-molecular weight substances, concurrently accompanied by a decline in the AOS activity.

The Role of Oxidative Stress in Tumorigenesis and Progression.

Oxidative stress refers to the imbalance between the production of reactive oxygen species (ROS) and the endogenous antioxidant defense system. Its involvement in cell senescence, apoptosis, and series diseases has been demonstrated. Advances in carcinogenic research have revealed oxidative stress as a pivotal pathophysiological pathway in tumorigenesis and to be involved in lung cancer, glioma, hepatocellular carcinoma, leukemia, and so on. This review combs the effects of oxidative stress on tumorigenesis on each phase and cell fate determination, and three features are discussed. Oxidative stress takes part in the processes ranging from tumorigenesis to tumor death via series pathways and processes like mitochondrial stress, endoplasmic reticulum stress, and ferroptosis. It can affect cell fate by engaging in the complex relationships between senescence, death, and cancer. The influence of oxidative stress on tumorigenesis and progression is a multi-stage interlaced process that includes two aspects of promotion and inhibition, with mitochondria as the core of regulation. A deeper and more comprehensive understanding of the effects of oxidative stress on tumorigenesis is conducive to exploring more tumor therapies.

Nanomaterials-Induced Redox Imbalance: Challenged and Opportunities for Nanomaterials in Cancer Therapy.

Cancer cells typically display redox imbalance compared with normal cells due to increased metabolic rate, accumulated mitochondrial dysfunction, elevated cell signaling, and accelerated peroxisomal activities. This redox imbalance may regulate gene expression, alter protein stability, and modulate existing cellular programs, resulting in inefficient treatment modalities. Therapeutic strategies targeting intra- or extracellular redox states of cancer cells at varying state of progression may trigger programmed cell death if exceeded a certain threshold, enabling therapeutic selectivity and overcoming cancer resistance to radiotherapy and chemotherapy. Nanotechnology provides new opportunities for modulating redox state in cancer cells due to their excellent designability and high reactivity. Various nanomaterials are widely researched to enhance highly reactive substances (free radicals) production, disrupt the endogenous antioxidant defense systems, or both. Here, the physiological features of redox imbalance in cancer cells are described and the challenges in modulating redox state in cancer cells are illustrated. Then, nanomaterials that regulate redox imbalance are classified and elaborated upon based on their ability to target redox regulations. Finally, the future perspectives in this field are proposed. It is hoped this review provides guidance for the design of nanomaterials-based approaches involving modulating intra- or extracellular redox states for cancer therapy, especially for cancers resistant to radiotherapy or chemotherapy, etc.

Options for Topical Treatment of Oxidative Eye Diseases with a Special Focus on Retinopathies.

Antioxidants, usually administered orally through the systemic route, are known to counteract the harmful effects of oxidative stress on retinal cells. The formulation of these antioxidants as eye drops might offer a new option in the treatment of oxidative retinopathies. In this review, we will focus on the use of some of the most potent antioxidants in treating retinal neuropathies. Melatonin, known for its neuroprotective qualities, may mitigate oxidative damage in the retina. N-acetyl-cysteine (NAC), a precursor to glutathione, enhances the endogenous antioxidant defense system, potentially reducing retinal oxidative stress. Idebenone, a synthetic analogue of coenzyme Q10, and edaravone, a free radical scavenger, contribute to cellular protection against oxidative injury. Epigallocatechin-3-gallate (EGCG), a polyphenol found in green tea, possesses anti-inflammatory and antioxidant effects that could be beneficial in cases of retinopathy. Formulating these antioxidants as eye drops presents a localized and targeted delivery method, ensuring effective concentrations reach the retina. This approach might minimize systemic side effects and enhance therapeutic efficacy. In this paper, we also introduce a relatively new strategy: the alkylation of two antioxidants, namely, edaravone and EGCG, to improve their insertion into the lipid bilayer of liposomes or even directly into cellular membranes, facilitating their crossing of epithelial barriers and targeting the posterior segment of the eye. The synergistic action of these antioxidants may offer a multifaceted defense against oxidative damage, holding potential for the treatment and management of oxidative retinopathies. Further research and clinical trials will be necessary to validate the safety and efficacy of these formulations, but the prospect of antioxidant-based eye drops represents a promising avenue for future ocular therapies.

RETRACTED: Cladribine induces apoptosis, neuroinflammation, mitochondrial oxidative stress, tau phosphorylation and Aβ (1−42) pathway in the hippocampus: An in vivo approach

Cladribine is a purine nucleoside found to enhance toxic amyloid protein and cause memory impairment. Patients following chemotherapy treatment commonly suffer from cognitive deficits more prevalent in the elderly than adults. A previous research study revealed that cladribine has a high affinity to the brain, increases the level of amyloid precursor protein, and results in learning deficits. The study was designed to validate an animal model of cladribine administration to rats through mitochondrial oxidative stress, inflammation, apoptosis, tau phosphorylation, and amyloid-β (1–42) accumulation. In this study, all rats were orally given cladribine (0.5 and 1 mg/kg) for 28 days, resulting in impaired spatial memory confirmed by behavioural activity. On day 29, all rats were euthanized, and the hippocampal tissues were isolated and used for the estimation of neuroinflammatory markers, biochemicals parameters (glutathione, catalase, lipid peroxidation, and nitrite), amyloid-β (1–42) level, neurotransmitters, and nuclear factor kappa B analysis. Cladribine administration significantly elevated cytokines release, dysbalanced neurotransmitter concentration, and promoted the Aβ accumulation and hyperphosphorylation of tau protein. Our study outcome confirmed that cladribine produces cognitive impairment via activation of Nuclear factor kappa B, mitochondrial oxidative stress and dysbalanced of the endogenous antioxidant defence system.

Hydroxytyrosol produced by engineered Escherichia coli strains activates Nrf2/HO-1 pathway: An in vitro and in vivo study.

This study explores the biological effects of hydroxytyrosol (HT), produced by the metabolic engineering of Escherichia coli, in a series of in vitro and in vivo experiments. In particular, a metabolically engineered Escherichia coli strain capable of producing HT was constructed and utilized. HEK293 and HeLa cells were exposed to purified HT to determine non-toxic doses that can offer protection against oxidative stress (activation of Nrf2/HO-1 signaling pathway). Male CD-1 mice were orally supplemented with HT to evaluate (1) renal and hepatic toxicity, (2) endogenous system antioxidant response, and (3) activation of Nrf2/HO-1 system in the liver. HT protected cells from oxidative stress through the activation of Nrf2 regulatory network. Activation of Nrf2 signaling pathway was also observed in the hepatic tissue of the mice. HT supplementation was safe and produced differential effects on mice's endogenous antioxidant defense system. HT biosynthesized from genetically modified Escherichia coli strains is an alternative method to produce high-quality HT that exerts favorable effects in the regulation of the organism's response to oxidative stress. Nonetheless, further investigation of the multifactorial action of HT on the antioxidant network regulation is needed.

Liver protective effect of chloroform extract of Bauhinia purpurea leaves is attributed partly to its antioxidant action and the presence of flavonoids

Context Bauhinia purpurea L. (Fabaceae) is used in the Ayurvedic system to treat various oxidative-related ailments (e.g., wounds, ulcers etc.). Therefore, it is believed that the plant also has the potential to alleviate oxidative-related liver damage. Objective This study elucidates the hepatoprotective activity of chloroform extract of B. purpurea leaves (CEBP) in paracetamol (PCM)-induced liver injury (PILI) rats. Materials and methods Male Sprague-Dawley rats (n = 6) were pre-treated once daily (p.o.) with CEBP (50–500 mg/kg) for seven consecutive days before being administered (p.o.) a hepatotoxic agent, 3 g/kg PCM. Liver enzyme levels were determined from the collected blood, while the collected liver was used to determine the activity of endogenous antioxidant enzymes and for histopathological examination. CEBP was also subjected to radical scavenging assays and phytochemical analysis. Results CEBP significantly (p < 0.05) reversed the toxic effect of PCM by increasing the serum levels of AST and ALT, and the activity of endogenous catalase (CAT) and superoxide dismutase (SOD) while reducing the liver weight/body weight (LW/BW) ratio. Other than low TPC value and radical scavenging activity, CEBP had a high antioxidant capacity when evaluated using the oxygen radical absorbance capacity (ORAC) assay. UHPLC-ESI-MS analysis of CEBP showed the presence of flavonoids. Discussion and conclusions CEBP exerts its hepatoprotective activity through a non-free radical scavenging pathway that involves activation of the endogenous enzymatic antioxidant defense system. Further study is needed to identify the responsible bioactive compounds before the plant can be developed as a future alternative hepatoprotective medicament for clinical use.

Discovery of New D-Ring Modified Isosteviol Derivatives as Potent Cardioprotective Agents against Oxidative Stress-Trigged Damage.

Cardiovascular diseases (CVDs) are a major global health concern, and oxidative stress is known to play a central role in their pathogenesis. The identification of new agents capable of inhibiting oxidative stress presents a promising strategy for preventing and treating CVDs. Natural products and their derivatives offer a valuable source for drug discovery, and isosteviol, a readily available natural product, is known to exhibit cardioprotective effects. In this study, 22 new D-ring modified isosteviol derivatives were synthesized and evaluated for their cardioprotective effect in vivo using the zebrafish cardiomyopathy model. The findings revealed that derivative 4e exhibited the most potent cardioprotective effect, surpassing its parent compound isosteviol and the positive drug levosimendan. At 1 μM, derivative 4e significantly protected the cardiomyocytes from injury, while at 10 μM it effectively maintained normal heart phenotypes, preventing cardiac dysfunction in zebrafish. Further investigation demonstrated that 4e protected cardiomyocytes from oxidative stress-induced damage by inhibiting reactive oxygen species overaccumulation, activating superoxide dismutase 2 expression, and enhancing the endogenous antioxidant defense system. These results suggest that isosteviol derivatives, particularly 4e, have the potential to serve as a novel class of cardioprotective agents for the prevention and treatment of CVDs.

STUDY OF THE CONTENT OF POLYPHENOLS AND ANTIOXIDANT ACTIVITY OF THE EXTRACT OF GREEN MARINE ALGAE ULVA LACTUCA L.

It was studied the impact of a water-alcohol extract (70%) from the marine green algae Ulva lactuca L., enriched with a polyphenol fraction, and a herbal preparation – extract of Eleutherococcus senticosus (Rupr. &amp; Maxim.) Maxim. (Araliaceae) on the indicators of antioxidant protection of the liver and blood plasma of rats under acute stress (vertical fixation by the dorsal neck fold). The total polyphenols and flavonoids content in the extract of U. lactuca made 16.2±1.8 µg GAE/g and 9.10±1.87 g QE/g, respectively, which was 2 times higher than its amount in the Eleutherococcus extract – 7.6±0.25 µg GAE/g and 4.8±0.3 µg QE/g respectively. The antiradical activity against ABTS+ and alkyl-peroxyl radicals of the U. lactuca extract was also almost 2 times higher in compere with Eleutherococcus. The pharmacological effect of the phenolic complex of U. lactuca in Wistar rats under stress was manifested in the stabilization of the antioxidant defense system. It was noted a decrease of the malondialdehyde content, an increase of the antiradical activity level, reduced glutathione content and the activity of enzymes of glutathione cycle in the liver and blood plasma of rats. In terms of efficiency, the extract of U. lactuca was not inferior to the reference preparation Eleutherococcus, and in terms of the ability to restore the activity of antioxidant enzymes and indicators of the glutathione system, it was superior to that. The pharmacological effect of the phenolic complex of U. lactuca, to our opinion, is provided by the action of its constituent flavonoids, phenolic terpenoids, phenolic acids (hydroxybenzoic, hydroxycinnamic, coumaric, synapic), etc., which have pronounced antioxidant properties, which prevents the development of lipid peroxidation and oxidative stress. Thus, the marine green algae U. lactuca is a promising raw material for the development of preparations that can increase the potential of the endogenous antioxidant defense system of the body at stress-induced disorders.

Response of the Endogenous Antioxidant Defense System Induced in RAW 264.7 Macrophages upon Exposure to Dextran-Coated Iron Oxide Nanoparticles.

Presently, iron oxide nanoparticles are the only ones approved for clinical use as contrast agents in magnetic resonance imaging (MRI). Even though there is a high demand for these types of nanoparticles both for clinical use as well as for research, there are difficulties in obtaining stable nanoparticles with reproducible properties. In this context, in this study, we report the obtaining by an adapted coprecipitation method of dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs). The morphology and structure of the dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) were determined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The TEM and SEM micrographs highlighted the obtaining of particles of nanometric size and spherical shape morphology. Furthermore, the high-resolution transmission electron microscopy (HRTEM), as well as selected area diffraction (SAED), revealed that the obtained samples presented the structure of cubic maghemite. In this study, we also explored the effects of the co-precipitation synthesized dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) on the redox status of macrophages. For cytotoxicity evaluation of these NPs, murine macrophages (RAW 264.7 cell line) were exposed to different concentrations of dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) corresponding to 0-500 μg Fe3+/mL and incubated for 24, 48, and 72 h. Intracellular iron uptake, changes in the oxidative stress parameters (reactive oxygen species production and malondialdehyde level), and the activity of antioxidant enzymes, as well as GSH concentration in cells, were evaluated after incubation with a lower (50 μg Fe3+/mL) and higher (500 μg Fe3+/mL) dose of NPs. The results indicated a significant decrease in RAW 264.7 cell viability after 72 h in the presence of NPs at concentrations above 25 μg Fe3+/mL. An important accumulation of NPs, dependent on dose and exposure time, was detected in macrophages, but it induced only a limited raise in the oxidative status. We showed here that the antioxidant capacity of RAW 264.7 macrophages was efficient in counteracting dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) toxicity even at higher doses.

The Analysis of Antioxidant Activity and Capacity of Boiled and Infused Indonesian Herbals

Antioxidants from natural ingredients such as medicinal plants are crucial to improving endogenous antioxidant defense system. The aim of the study was to evaluate the antioxidant activity and capacity of boiled and infused Indonesian herbals using DPPH (2,2-iphenyl-1- picrylhydrazyl) assay. The DPPH assay was conducted with triplicate repetitions to 10 herbals (Phyllanthus niruri, Lantana camara, Piper crocatum, Curcuma xanthorrhiza, Moringa oleifera, Tamarindus indica, Kaempferia galanga, Citrus aurantifolia, Hibiscus sabdariffa, and Zingiber officinale), each consisting of boiled and infused samples. The antioxidant activities of those herbals were (boiled and infused samples, respectively): 91.88 %, 91.30 % (P. niruri), 92.14 %, 86.60 % (L. camara), 53.39 %, 58.99 % (P. crocatum), 18.73 %, 20.86 % (C. xanthorrhiza), 51.35 %, 59.96 % (M. oleifera), 63.60 %, 16.95 % (T. indica), 13.14 %, 18.82 % (K. galanga), 20.46 %,69.24 %. (C. aurantifolia), 34.49 %, 34.40 % (H. sabdariffa), and 27.16 %, 26.01 % (Z. officinale). P. niruri and L. camara reached the high R2 value. P. niruri and L. camara reached the stable antioxidant activity after 50 minutes, while the other herbals after 60 minutes. P. niruri and L. camara were the 2 herbals with the highest antioxidant activity and slightly lower antioxidant capacity. The other herbals had lower antioxidant activity and higher antioxidant capacity. There was no significant difference in antioxidant activity between boiled and infused samples of all herbals, except T. indica and C. aurantifolia.

Mercury Chloride Affects Band 3 Protein-Mediated Anionic Transport in Red Blood Cells: Role of Oxidative Stress and Protective Effect of Olive Oil Polyphenols.

Mercury is a toxic heavy metal widely dispersed in the natural environment. Mercury exposure induces an increase in oxidative stress in red blood cells (RBCs) through the production of reactive species and alteration of the endogenous antioxidant defense system. Recently, among various natural antioxidants, the polyphenols from extra-virgin olive oil (EVOO), an important element of the Mediterranean diet, have generated growing interest. Here, we examined the potential protective effects of hydroxytyrosol (HT) and/or homovanillyl alcohol (HVA) on an oxidative stress model represented by human RBCs treated with HgCl2 (10 µM, 4 h of incubation). Morphological changes as well as markers of oxidative stress, including thiobarbituric acid reactive substance (TBARS) levels, the oxidation of protein sulfhydryl (-SH) groups, methemoglobin formation (% MetHb), apoptotic cells, a reduced glutathione/oxidized glutathione ratio, Band 3 protein (B3p) content, and anion exchange capability through B3p were analyzed in RBCs treated with HgCl2 with or without 10 μM HT and/or HVA pre-treatment for 15 min. Our data show that 10 µM HT and/or HVA pre-incubation impaired both acanthocytes formation, due to 10 µM HgCl2, and mercury-induced oxidative stress injury and, moreover, restored the endogenous antioxidant system. Interestingly, HgCl2 treatment was associated with a decrease in the rate constant for SO42- uptake through B3p as well as MetHb formation. Both alterations were attenuated by pre-treatment with HT and/or HVA. These findings provide mechanistic insights into benefits deriving from the use of naturally occurring polyphenols against oxidative stress induced by HgCl2 on RBCs. Thus, dietary supplementation with polyphenols might be useful in populations exposed to HgCl2 poisoning.