Reduction Of Oxidative Stress Research Articles

The differential effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors: an updated systematic review of randomized controlled trials.

Cardiovascular disease remains a major global health concern. The combination of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been shown to beneficially modify a range of cardiovascular risk factors. However, whether EPA and DHA have differential effects or potencies is currently unclear. A systematic review of randomized controlled trials (RCTs) that compared ≥2 g/day of near pure EPA and DHA was conducted. A total of 24 publications from nine unique RCTs were included. EPA and DHA both lower triglyceride levels, with DHA most likely having a slightly greater effect. Furthermore, both EPA and DHA increase high density lipoprotein (HDL) 2 cholesterol, which is cardioprotective, with the increase being greater with DHA. DHA appears to increase low density lipoprotein (LDL) cholesterol; however, DHA also increases LDL particle size, which would render LDL less atherogenic. DHA seems more effective than EPA in decreasing heart rate and blood pressure. Both EPA and DHA alter platelet function decreasing thrombogenicity, although they may have different actions on platelets. Both EPA and DHA decrease F2-isoprostanes, interpreted as a reduction in oxidative stress. They both decrease inflammatory gene expression and promote an anti-inflammatory oxylipin profile. These are all favorable effects with regard to cardiovascular disease risk. Effects of EPA and DHA on blood glucose are inconsistent. This review is constrained by the small number of high quality RCTs that directly compare EPA to DHA and report on outcomes other than blood lipids. There is a need for additional high-quality research to assess the independent effects of EPA and DHA on cardiovascular risk factors (e.g., inflammation, blood pressure, vascular function, platelet function) in larger and more diverse study populations.

Effects of Yishentongluo Recipe on Nrf2 and HO-1 pathway activation leading to reduction of oxidative stress and kidney fibrosis in membranous nephropathy rat model

This study investigated Yishentongluo Recipe (YSTLF) effects on renal oxidative stress and fibrosis in membranous nephropathy (MN) rats. MN was induced by cationized bovine serum albumin injection. Rats were divided intocontrol, MN, YSTLF, and benazepril groups. After four weeks of treatment, urine protein levels (UTP), serum total cholesterol (TC), triglycerides (TG), total protein (TP), and albumin (ALB) were assessed. Kidney microstructure, IgG immune complex deposition, and protein expressions of superoxide dismutase (SOD), malondialdehyde (MDA), transforming growth factor β1 (TGF-β1), collagen I (Collagen-I), α-smooth muscle actin (α-SMA), nuclear factor E2-related factor (Nrf2), haem oxygenase 1 (HO-1), and NADPH oxidase 4 (NOX4) were evaluated. YSTLF and BNPL treatments reduced UTP, TC, TG, increased TP and ALB levels, downregulated TGF-β1, Collagen-I, and α-SMA, and upregulated Nrf2, HO-1, and NOX4. YSTLF partially reversed SOD reduction and MDA elevation, suggesting its efficacy in alleviating renal oxidative stress and fibrosis in MN rats via Nrf2/HO-1 signaling pathway activation.

Novel derivative of nicotinic acid ameliorates doxorubicin-induced cardiac injury via regulation of redox homeostasis

Introduction: Doxorubicin (DOX) is an anthracycline antibiotic with considerable significance in clinics as an anticancer agent, which is limited by its cardiotoxicity, though. A large number of possible therapeutic strategies for reducing cardiotoxicity with doxorubicin have been studied. However, none of them fully meets the requirements of clinical practice. The aim of the study: to evaluate the cardioprotective effects of a new original heterocyclic compound, a pyridine-3-carboxylic acid derivative potassium 5-hydroxynicotinate. Materials and Methods: Cardiac injury was induced by intraperitoneal administration of doxorubicin (DOX) at a dose of 20 mg/kg. After 48 hours, the parameters of left ventricular contractility and StTTI coefficient were assessed on isolated heart in the Langendorff system under the conditions of 480 beats per minute for 11 seconds. Additionally, specific markers of myocardial injury were determined. The lipid peroxidation products and SOD activity were measured as well to challenge whether the compound is able to reduce oxidative stress. Results: The study showed that pretreatment by potassium 5-hydroxynicotinate (35 mg/kg, 48 h) attenuated DOX-induced damage, resulting in a significant decrease in the StТТI coefficient to 3.3 values and in the restoration of the antioxidant activity of enzymes. Conclusion: The obtained data totally demonstrate the protective effects of potassium 5-hydroxynicotinate in DOX-induced cardiomyopathy. A significant role in potassium 5-hydroxynicotinate-mediated cardioprotection is, apparently, related to the reduction of oxidative stress and down-regulation of the level of intracellular calcium.

Astaxanthin: a novel antioxidant for polycystic ovary syndrome?

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder and the most prevalent gynecological condition among women of reproductive age. Current treatment options primarily focus on managing symptoms and fail to fully prevent long-term complications. Astaxanthin (ASX), a red carotenoid pigment, is known for its potent antioxidant, anti-inflammatory, anti-proliferative, and anti-apoptotic properties. This review aims to evaluate the efficacy of astaxanthin supplementation in PCOS management. Our team conducted a comprehensive search of relevant databases up to May 2024, including human clinical trials and animal studies investigating astaxanthin’s effects on PCOS. Of the 45 articles retrieved, 8 met the inclusion criteria (4 animal studies and 4 clinical trials). The majority of the studies demonstrated that astaxanthin has a beneficial impact on ovarian histo morphology and follicular development, with notable reductions in oxidative stress and inflammation among patients with PCOS. Although astaxanthin showed improvement in dyslipidemia, it had no significant effect on weight loss. It is suggested that astaxanthin’s therapeutic potential in PCOS is primarily due to its antioxidant and anti-inflammatory properties rather than its effects on weight. Thus, astaxanthin may be considered a promising therapeutic agent for alleviating PCOS complications; however, further research is warranted due to the limited availability of high-quality clinical trials.

Dysfunction of Endothelial Cell-Mediated Intercellular Communication and Metabolic Pathways in Age-Related Macular Degeneration

Purpose Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, but the therapies are not satisfactory. This study aimed to find AMD specific features through the analysis of high-throughput sequencing. Methods In this study, we integrated six projects containing single-cell RNA sequencing (scRNA-seq) data to perform a comprehensive analysis for AMD samples in the tissues of retina and retinal pigment epithelium/choroid, and in the positions of macula and periphery. Differentially expressed genes (DEGs) were analyzed and crucial signaling pathways were identified across cell types and between the macula and periphery. The intercellular signaling transduction among cell types were inferred by "CellChat" to build cell–cell communication network under normal and AMD conditions, and verified at the transcriptional level. The CD31+ endothelial cells were obtained to evaluate the enrichment of KEGG pathways in atrophic and neovascular AMD, and GSVA was adopted to discover differential metabolic signals in each AMD type. Results Thirteen major cell types were identified in the integrated scRNA-seq data. Although no disease-specific cell type or differential cell proportion was found, DEGs and enriched pathways were shown in cell-type- and position-dependent manners. Severe impairment of endothelial cell-mediated cell interactions was found in the signaling transduction network of the macula, and compromised cell interactions were observed in the periphery. Furthermore, distinct signaling pathways and metabolic states were uncovered in atrophic and neovascular AMD. Striking reduction in energy metabolism, lipid metabolism, and oxidative stress was indicated in the atrophic AMD. Conclusion Conclusively, we discover aberrant signals and metabolic pathways in AMD samples, providing insight into mechanisms and potential therapeutic targets for the AMD treatment.

Enzyme-delivery Metal-organic Framework Composite Coatings for Restoration of Hyperglycemia-damaged Osteoblast Differentiation

There is a significant clinical need to develop effective treatments for bone defects in patients with diabetes mellitus (DM), as they are at higher risk of fractures and impaired healing. Guided bone tissue engineering using biocompatible and biodegradable polymers is a promising approach. However, current diabetic bone regenerative therapies often fail due to the accumulation of advanced glycation products, which can affect the integration of traditional tissue engineering scaffolds with native bone. Therefore, novel approaches are needed to improve the efficacy of diabetic bone regeneration. This study presents a proof-of-concept development of a multifunctional polymer composite coating tailored towards restoring diabetes-related damage in osteoblast differentiation. Our composite system involves 3D-printed poly(caprolactone fumarate) (PCLF) and poly(caprolactone) (PCL) blend scaffolds coated with multifunctional chitosan methacrylate (chiMA). The chiMA coating is embedded with a sustained-release formulation of glucose oxidase (GOx) from MIL-127 metal-organic frameworks making the coating a stimuli-responsive biomolecule delivery system. The multifunctional coating is designed for the sustained release of GOx and sodium pyruvate for in vitro glucose modulation and oxidative stress reduction, respectively. We propose that sustained release of GOx from MIL-127 embedded chiMA coatings can modulate the high glucose (HG) cellular milieu towards normal glucose (NG), enhancing osteoblast (OB) differentiation via downstream effects. Our results show successful synthesis of MIL-127, encapsulation of GOx, and fabrication of composite coating on the PCLF/PCL scaffolds with effective enzyme activity measured as a function of lowering glucose concentration in HG media for 144 h to normal levels. In vitro evaluation of OB viability, attachment, proliferation, and differentiation showed an overall decrease in cellular activity in HG conditions, which was restored through the glucose-modulating functionality of the GOx-releasing MIL-127 coatings. Our results also presented preliminary evidence of a statistical correlation between DM-related gene markers and osteogenic markers in vitro that requires further exploration. Although this proof-of-concept study holds promise for advancing precision biomaterials development for diabetic tissue engineering and meeting the unmet clinical need for effective treatments and warrants future in vivo evaluation of the composite coating and molecular biology understanding of correlations between DM and osteogenic markers.

Dietary EPA and DHA enrichment of a high fat diet during doxorubicin-based chemotherapy attenuated neuroinflammatory gene expression in the brain of C57bl/6 ovariectomized mice

Chemotherapy agents in breast cancer are associated with chemotherapy-related cognitive impairments (CRCI). Mechanisms are not fully clear, but alterations of glucose and lipid metabolism, neuroinflammation and neurodegeneration may contribute to CRCI. The aim of this study was to investigate the combined effects of a high fat (HF) diet combined with doxorubicin-based chemotherapy on glucose and lipid metabolism, neuroinflammation, and neurodegeneration in mice. Additionally, we examined the therapeutic potential of dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to attenuate these effects. Female C57Bl/6 mice (n = 42) were fed HF, HFn-3 (2 % kcals as EPA + DHA) or Low Fat (LF) diets for seven weeks, with and without chemotherapy. In this study, two chemotherapy injections led to weight and body fat loss associated with a decrease in insulin resistance measured by HOMA-IR. HOMA-IR was significantly greater in HF versus LF groups; but HOMA-IR in HFn-3 group did not significantly differ from either HF or LF groups. Chemotherapy resulted in higher brain concentrations of the inflammatory chemokine KC/GRO. Compared to LF diet plus chemotherapy, HF diet plus chemotherapy upregulated multiple genes involved in neuroinflammation and neurodegeneration pathways. HFn-3 diet plus chemotherapy attenuated gene expression by downregulating multiple genes involved in neuroinflammation and blood brain barrier regulation, including Mapkapk2, Aqp4, and s100b, and upregulating Kcnb1 and Atxn3, genes involved in reduction of oxidative stress and anxiety, respectively. Overall, a HF diet combined with chemotherapy is associated with neuroinflammatory and neurodegenerative gene expression changes in this mouse model; dietary enrichment of EPA and DHA attenuated these effects. Further studies are needed to understand how diet impacts behavioral outcomes of CRCI.

Will melatonin supplementation become a new form of obesity treatment? A review of recent literature.

Background: In 2020, the World Health Organization (WHO) estimated that 650 million adults worldwide are obese, and 2.8 billion individuals struggle with overweight. Obesity is associated with an increased risk of cardiovascular diseases, type 2 diabetes, heart disease, adverse effects on mental health, the development of certain cancers, and other conditions. In recent years, there has been growing interest in the role of melatonin, which has therapeutic potential in the treatment of obesity. Studies suggest that melatonin supplementation may lead to weight reduction and improvement in metabolic parameters, significantly reduce cardiovascular disease risk factors, and enhance insulin sensitivity in obese individuals. Aim of study: This review aims to present the latest scientific findings on the impact of melatonin supplementation on the development of obesity and its complications. We focus primarily on the mechanisms of melatonin's action in the context of obesity, particularly on potential pathways that have not yet been thoroughly explored. Our aim is to provide deeper insights into research on obesity and its prevention. Materials and Methods: Search was conducted using PubMed and Google Scholar databases, utilizing the keywords "obesity," "melatonin," and "weight loss" in various configurations. The review primarily considers studies published after 2016 that are available online. Summary Melatonin supplementation leads to a statistically significant reduction in blood glucose levels and an increase in cellular insulin sensitivity. Its promising properties in the treatment of obesity have been demonstrated through the reduction of oxidative stress, indicating a potential adjunct for weight loss. Based on the cited studies, the beneficial effects of melatonin supplementation on cardiovascular risk factors have been confirmed. Melatonin could be considered as an adjunctive therapy for obese individuals who do not respond to other treatment modalities.

Potential of Sulodexide in the Treatment of Diabetic Retinopathy and Retinal Vein Occlusion.

Retinal vascular diseases, such as diabetic retinopathy or retinal vein occlusion, are common causes of severe vision loss. Central to the pathophysiology of these conditions are endothelial dysfunction, inflammation, capillary leakage, ischemia, and pathological neoangiogenesis. Capillary damage leads to leakage and the development of macular edema, which is associated with vision loss and requires complex treatment. Sulodexide, a glycosaminoglycan composed of heparan sulfate and dermatan sulfate with high oral bioavailability, exhibits several favorable pharmacologic properties, including antithrombotic, anti-inflammatory, and endothelium-protective effects. Additionally, treatment with sulodexide has been associated with the reduction of oxidative stress and decreased expression of angiogenic growth factors, such as vascular endothelial growth factor. This review aims to provide an overview of the pharmacological properties, mechanisms of action, and therapeutic effects of sulodexide. Furthermore, its potential for clinical application in venous and diabetic diseases, such as venous thromboembolism, chronic venous insufficiency, peripheral artery disease, or diabetic nephropathy, is summarized. We also present experimental and clinical studies evaluating the potential of sulodexide in ocular conditions and discuss its therapeutic implications for the treatment of retinal vascular diseases.

Interleukin(IL)-37 attenuates isoproterenol (ISO)-induced cardiac hypertrophy by suppressing JAK2/STAT3-signaling associated inflammation and oxidative stress

BackgroundInflammation and oxidative stress have drawn more and more interest in the realm of cardiovascular disease. In many different disorders, IL-37 acts as an anti-inflammatory and suppressor of inflammation. This study aimed to investigate whether IL-37 could alleviate cardiac hypertrophy by reducing inflammation and oxidative stress. MethodsIn vivo, a cardiac hypertrophy model was induced by 14 d of daily isoproterenol (ISO, 30 mg/kg/d) injection, followed by weeks of treatment with recombinant human IL-37 (1000 ng/animal), administered three times weekly. Assessments concentrated on markers of inflammation and oxidative stress, apoptosis, myocardial disease, and cardiac shape and function. In vitro, neonatal rat cardiomyocytes (NRCMs) were subjected to ISO (10 µM) to establish a cardiomyocytes hypertrophy model. Subsequent IL-37 treatment (100 ng/ml) was applied to determine its cardioprotective efficacy and to elucidate further the underlying mechanisms involved. ResultsSignificant cardioprotective benefits of IL-37 were seen (in vitro as well as in vivo), primarily through the reduction of oxidative stress, inflammation, apoptosis, and heart hypertrophy markers. Furthermore, IL-37 treatment was associated with a decrease in JAK2 and STAT3 phosphorylation. It is interesting to note that WP1066, a JAK2/STAT3 inhibitor, exhibited antioxidant and anti-inflammatory properties comparable to IL-37, as well as synergistic effects when mixed with the latter. ConclusionISO-induced cardiac hypertrophy is lessened by IL-37 through the reduction of oxidative stress and inflammation. Additionally, the effects of IL-37 are closely related to inactivation of the JAK2/STAT3 signaling pathway. It is anticipated that IL-37 will one day be used to treat cardiovascular illnesses such as heart hypertrophy.

Biocatalytic Clusterzyme Patches Restore Lung Function via Immunomodulation and Mitochondria Protection.

Currently, pulmonary complications such as lung infections during the perioperative period are still the main cause of prolonged hospitalization and death in patients with lung injury due to the lack of effective drugs. Clusterzyme, a kind of artificial enzyme with a high enzyme-like activity and safety profile, exhibits good effects on reducing oxidative stress and immunomodulation. Here, we present the functionalized patches that is administered on the lung airways and rescues the injured organ via clusterzymes. The long-term antioxidant capacity of the patches significantly ameliorated lipopolysaccharide-induced lung function impairment with a significant reduction in lung goblet cell metaplasia and oxidative stress. The inflammatory factors such as cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α levels decreased by 50%, while the mtDNA copy number increased by 50% and ATP production increased by 100%. Mice lung function was significantly improved, suggesting that the patches can rescue lung injury by modulating oxidative stress and immune responses as well as protecting the mitochondria, providing an avenue for effective intervention of lung injury.

The Therapeutic Potential of Theobromine in Obesity: A Comprehensive Review.

Obesity, characterized by chronic low-grade inflammation, is a significant health concern. Phytochemicals found in plants are being explored for therapeutic use, particularly in combating obesity. Among these, theobromine, commonly found in cocoa and chocolate, shows promise. Although not as extensively studied as caffeine, theobromine exhibits positive effects on human health. It improves lipid profiles, aids in asthma treatment, lowers blood pressure, regulates gut microbiota, reduces tumor formation, moderates blood glucose levels, and acts as a neuroprotective agent. Studies demonstrate its anti-obesity effects through mechanisms such as browning of white adipose tissue, activation of brown adipose tissue, anti-inflammatory properties, and reduction of oxidative stress. This study aims to suggest theobromine as a potential therapeutic agent against obesity-related complications.

Emoxypine succinate modulates behavioral and molecular responses in zebrafish model of iron Overload-Induced neuroinflammation via CDK5/GSK3- β and NLRP3 inflammasome pathway

Excessive iron accumulation in the brain plays a significant role in neurodegenerative processes, contributing to the pathogenesis of Alzheimer’s disease (AD). AD, a prominent neurological disorder affecting the central nervous system, is characterized by the accumulation of beta-amyloid (Aβ) and tau phosphorylation. This accumulation leads to the subsequent development of cognitive impairments, particularly in learning and memory functions. This study investigates the neuroprotective effects of emoxypine succinate in a zebrafish model of iron overload-induced neurodegeneration. Iron was administered to the zebrafish for 28 days to induce neurodegeneration. Following induction, Emoxypine succinate was employed as a treatment intervention for 14 days (concentrations of 4 mg/L, 8 mg/L, and 12 mg/L). Following the end of the treatment, behavioral tests (Y maze test, Novel tank test) were conducted on the zebrafish, and the biochemical (MDA, Catalase, SOD, GSH) and molecular parameters (AchE, Iron levels, IL-1β, TNF-α, CDK-5, GSK-3β, and NLRP3) of the zebrafish brain were also assessed. In the novel tank test, emoxypine succinate-treated groups exhibited significantly increased time in the upper zone (p < 0.001), higher distance travelled (p < 0.001), and shorter latency to the top (p < 0.001) compared to the negative control. Similarly, the Y-maze test revealed improved time in the novel arm (p < 0.001) and total distance travelled (p < 0.001) in treated groups versus the negative control. Assessment of oxidative stress parameters demonstrated significant reductions in oxidative stress in emoxypine succinate-treated groups. Furthermore, AChE activity decreased significantly (p < 0.001), and brain iron levels decreased substantially (p < 0.001) in treated groups, indicating positive therapeutic outcomes. Molecular analysis showed a significant reduction in pro-inflammatory markers like IL-1β, TNF-α, CDK-5, GSK-3β, and NLRP3 (p < 0.001). This comprehensive study highlights the potential efficacy of emoxypine succinate in mitigating neurodegeneration associated with iron dysregulation.

Serum-Free Media Formulation Using Marine Microalgae Extracts and Growth Factor Cocktails for Madin-Darby Canine Kidney and Vero Cell Cultures.

The development of serum-free media (SFM) is critical to advance cell culture techniques used in viral vaccine production and address the ethical concerns and contamination risks associated with fetal bovine serum (FBS). This study evaluated the effects of marine microalgal extracts and growth factor cocktails on the activity of Madin-Darby canine kidney (MDCK) and Vero cells. Five marine microalgal species were used: Spirulina platensis (SP), Dunaliella salina (DS), Haematococcus pluvialis (HP), Nannochloropsis salina (NS), and Tetraselmis sp. (TS). DS and SP extracts significantly increased the proliferation rate of both MDCK and Vero cells. DS had a proliferation rate of 149.56% and 195.50% in MDCK and Vero cells, respectively, compared with that in serum-free medium (SFM). Notably, DS and SP extracts significantly increased superoxide dismutase (SOD) activity, which was 118.61% in MDCK cells and 130.08% in Vero cells for DS, and 108.72% in MDCK cells and 125.63% in Vero cells for SP, indicating a reduction in intracellular oxidative stress. Marine microalgal extracts, especially DS and SP, are feasible alternatives to FBS in cell culture as they promote cell proliferation, ensure safety, and supply essential nutrients while reducing oxidative stress.

The protective effects of Acorus calamus L. rhizome extracts against rheumatoid arthritis-associated dyslipidemia, oxidative stress, and liver injury in rats

ABSTRACT Rheumatoid arthritis (RA) is associated with comorbidities like dyslipidemia and liver damage. Acorus calamus L. is commonly used to treat inflammatory and hepatorenal ailments. Herein, we assessed the hypolipidemic and hepatoprotective activities of A. calamus rhizome extracts in adjuvant-induced arthritis (AIA) in rats. A. calamus rhizome’s methanol (AME) and n-hexane (AHE) extracts were prepared. In vivo, fifty-four female Wistar rats were allocated into nine groups (n = 6). The AIA was induced by injecting Complete Freund’s adjuvant (100 µL, s.c.) into the rat’s right hind paw. After AIA induction, animals were orally treated with meloxicam (MEL; 3 mg/kg) and graded doses (125, 250, and 500 mg/kg) of AME and AHE for 28 consecutive days. Results showed that both plant extracts dose-dependently restored the body weight and liver index of arthritic rats. Each plant extract significantly (p < 0.05) attenuated hyperlipidemia and atherogenicity in arthritic rats. They also normalized the liver function markers and protein concentrations along with the reduction in hepatic oxidative stress. Histopathological examination of the liver supported the biochemical findings. However, AME exhibited better pharmacological activities than AHE. Our findings conclude that A. calamus rhizome could be used to treat dyslipidemia and liver injury in inflammatory conditions like RA.

Experimental study of radioprotective properties of lithium pyruvate in vitro

Radiotoxicity is a serious problem for patients undergoing radiotherapy, so the search for new radioprotective drugs to mitigate its effects is highly relevant. Radioprotectors should have a number of properties, including direct antioxidant action, reduction of oxidative stress, ability to induce DNA repair or inhibit apoptosis, and at the same time not cause their own side effects. Antioxidants based on lithium salts look promising in terms of their properties. The aim of study was to study the radioprotective properties of lithium pyruvate in vitro. Material and Methods. Relatively radiosensitive blood mononuclear cells and relatively radioresistant fibroblasts of 3T3L1 line were used as biomodels for x-ray exposure. Cells were incubated and irradiated in 96-well plates. Lithium pyruvate was used at a final concentration of 1.2 mM. Cells were irradiated at a dose rate of 15 mGy/s in the absorbed-dose range from 0 to 5 Gy using an x-ray unit (anode voltage: 160 kV, average current: 3.5 mA). Cell viability was assessed by MTT test and resazurin test. The evaluation of cell death variants and the level of oxidative stress were determined by cytofluorimetric method. Results. The cytoprotective effect of lithium pyruvate was established. Cytoprotection was manifested in the increased cell survival and decreased oxidative stress level under lithium pyruvate after x-ray in a wide range of absorbed doses. Relatively high efficiency was shown in relation to blood mononuclear cells with an increase in the viable fraction by 5–7 % and a decrease in oxidative stress level during irradiation in the range of 1.0–3.0 Gy. Apoptosis was found to be the main mechanism of cell death after irradiation. Lithium pyruvate reduced the level of apoptosis in cell population under irradiation and chemically induced oxidative stress. Conclusion. Radioprotective effect of lithium pyruvate under x-ray irradiation in vitro has been shown. Reduction of oxidative stress under the action of pyruvate provides a pathogenetic basis for the potential use of this compound as a radioprotector, which requires further studies on in vivo models.

Cardioprotective Effects of Phlorizin on Hyperlipidemia-induced Myocardial Injury: Involvement of Suppression in Pyroptosis via Regulating HK1/NLRP3/Caspase-1 Signaling Pathway.

Hyperlipidemia (HLP) is a prevalent and intricate condition that plays a pivotal role in impairing heart function. The primary objective of this study was to assess the lipid-lowering and cardioprotective properties of phlorizin (PHZ) and to investigate its potential molecular mechanisms in rats. In this investigation, Sprague-Dawley rats were subjected to a high-fat diet for a period of 28days to induce an HLP model. Subsequently, the rats received oral doses of PHZ or metformin from day 14 to day 28. We assessed various parameters using commercially available kits, including serum lipid deposition, myocardial injury biomarkers, oxidative stress markers, and inflammatory cytokine levels. We also employed electron microscopy to examine myocardial ultrastructural changes and conducted Western blot analyses to assess apoptosis factors and pyroptosis markers. Comparing the PHZ group with the model group, we observed significant improvements in blood lipid deposition and heart injury biomarkers. Furthermore, PHZ demonstrated a clear reduction in myocardial tissue oxidative stress and inflammatory factors, as well as a suppression of cell apoptosis. Subsequent investigations indicated that PHZ treatment led to a decreased inflammatory response and lowered levels of hexokinase 1 (HK1), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and Caspase-1. In summary, PHZ proved to be an effective remedy for alleviating HLP-induced cardiac damage by reducing blood lipid levels, mitigating oxidative stress, curbing inflammation, and suppressing pyroptosis. The inhibition of pyroptosis by PHZ appears to be linked to the regulation of the HK1/NLRP3/Caspase-1 signaling pathway.

SGLT2 inhibition mitigates transition from acute kidney injury to chronic kidney disease by suppressing ferroptosis

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to be renoprotective in ischemia-reperfusion (I/R) injury, with several proposed mechanisms, though additional mechanisms likely exist. This study investigated the impact of luseogliflozin on kidney fibrosis at 48 h and 1 week post I/R injury in C57BL/6 mice. Luseogliflozin attenuated kidney dysfunction and the acute tubular necrosis score on day 2 post I/R injury, and subsequent fibrosis at 1 week, as determined by Sirius red staining. Metabolomics enrichment analysis of I/R-injured kidneys revealed suppression of the glycolytic system and activation of mitochondrial function under treatment with luseogliflozin. Western blotting showed increased nutrient deprivation signaling with elevated phosphorylated AMP-activated protein kinase and Sirtuin-3 in luseogliflozin-treated kidneys. Luseogliflozin-treated kidneys displayed increased protein levels of carnitine palmitoyl transferase 1α and decreased triglyceride deposition, as determined by oil red O staining, suggesting activated fatty acid oxidation. Luseogliflozin prevented the I/R injury-induced reduction in nuclear factor erythroid 2-related factor 2 activity. Western blotting revealed increased glutathione peroxidase 4 and decreased transferrin receptor protein 1 expression. Immunostaining showed reduced 4-hydroxynonenal and malondialdehyde levels, especially in renal tubules, indicating suppressed ferroptosis. Luseogliflozin may protect the kidney from I/R injury by inhibiting ferroptosis through oxidative stress reduction.

Agonistes des récepteurs GLP-1 dans la maladie d’Alzheimer : Potentiel thérapeutique et mécanismes d’action

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by progressive cognitive decline and neuronal dysfunction. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for the treatment of type 2 diabetes, have demonstrated promising neuroprotective effects. This review aims to evaluate the effects and underlying mechanisms of GLP-1 RAs in the context of AD. A comprehensive search of databases yielded 622 articles, from which studies met the predefined inclusion criteria and were subjected to detailed analysis, 29 articles were deemed appropriate for analysis. The results indicate that GLP-1 RAs can significantly reduce amyloid-beta (Aβ) deposition and phosphorylated tau levels in the brains of AD patients. These neuroprotective effects are attributed to multiple synergistic mechanisms, including the enhancement of neuronal survival, reduction of oxidative stress, and attenuation of neuroinflammation. This review underscores the importance of further research to fully elucidate the mechanisms of GLP-1 RAs and their potential as a therapeutic strategy for AD.

House cricket protein hydrolysates alleviate hypertension, vascular dysfunction, and oxidative stress in nitric oxide-deficient hypertensive rats.

Edible insects with high protein content and bioactive peptides with health promotion against chronic disease. Deficiency of nitric oxide (NO) contributes to hypertension, a leading cause of cardiovascular diseases and death worldwide. This study assessed the antihypertensive effects of house cricket protein hydrolysates (HCPH) in NO-deficient hypertensive rats. Male Sprague-Dawley rats (n = 12/group) were hypertensive after the administration of Nω-nitro-L-arginine methyl ester (L-NAME) at a dose of 50 mg/kg body weight (BW)/day in drinking water for 7 weeks. The animals were then treated with HCPH (250 or 500 mg/kg BW/day) or lisinopril (Lis) (1 mg/kg BW/day) for the last 4 weeks of L-NAME administration. Blood pressure (BP), vascular function, and structural changes, endothelial NO synthase (eNOS), and p47phox nicotinamide adenine dinucleotide phosphate (NADPH) oxidase protein expression in aortic tissues, plasma nitrate/nitrite, plasma angiotensin-converting enzyme (ACE) activity, and oxidative stress markers in blood and tissues were evaluated. Induction of hypertension resulted in significantly elevated BP, decreased plasma nitrate/nitrite concentration, abolished vascular function, and increased vascular wall thickness. Overproduction of carotid and mesenteric superoxide, increased plasma, heart, and kidney malondialdehyde, and protein carbonyl levels, and increased plasma ACE activity were observed. Down-expression of eNOS with overexpression of p47phox NADPH oxidase subunit was also found in L-NAME hypertensive rats. Oral treatment with HCPH, particularly at a dose of 500 mg/kg BW/day, significantly alleviated these alterations in a manner comparable to that of Lis. HCPH improved vascular function and exerted antihypertensive effects, mainly due to the improvement of NO bioavailability, reduction of oxidative stress, and inhibition of ACE.