Cytoprotective Properties Research Articles

Long-Term Oral Administration of Salidroside Alleviates Diabetic Retinopathy in db/db Mice.

Diabetic retinopathy (DR), a microvascular complication of diabetes mellitus, is the leading cause of vision loss in the working-age population worldwide. Unfortunately, current clinical treatments cannot completely prevent the occurrence and development of DR. Salidroside (Sal) is a medicinal supplement that has antioxidative and cytoprotective properties. This study aimed to investigate the therapeutic effect of Sal on DR. Briefly, Sal treatment was applied to wide-type mice and db/db mice (a widely used diabetic mice) at 25 mg/kg by oral gavage once daily from 8 weeks to 20 weeks. Mice’s bodyweight, blood glucose, total cholesterol, triglyceride, high density lipoprotein and low density lipoprotein were recorded and analyzed. Retinal trypsin digestion and evans blue dye assay were used to detect retinal microvessel changes and function. Retinal glutathione and malondialdehyde content measurements were applied to assess retinal oxidative stress. Full-length transcriptome analysis was performed to explore the underlying mechanisms of Sal protection. Our results found that Sal treatment could successfully relieve blood glucose and blood lipid abnormalities, and reduce retinal oxidative stress level in diabetic mice. Also, Sal treatment repaired the abnormal transcriptome caused by diabetes, alleviated the microvascular lesion of the fundus in diabetic mice, and protected retinal normal barrier function. This study enriches the indications of Sal in the treatment of diabetic diseases, providing practical research ideas for the comprehensive preventions and treatments of DR.

Sulforaphane Ameliorates Metabolic Changes Associated With Status Epilepticus in Immature Rats.

Status epilepticus (SE) is a common paediatric emergency with the highest incidence in the neonatal period and is a well-known epileptogenic insult. As previously established in various experimental and human studies, SE induces long-term alterations to brain metabolism, alterations that directly contribute to the development of epilepsy. To influence these changes, organic isothiocyanate compound sulforaphane (SFN) has been used in the present study for its known effect of enhancing antioxidative, cytoprotective, and metabolic cellular properties via the Nrf2 pathway. We have explored the effect of SFN in a model of acquired epilepsy induced by Li-Cl pilocarpine in immature rats (12 days old). Energy metabolites PCr, ATP, glucose, glycogen, and lactate were determined by enzymatic fluorimetric methods during the acute phase of SE. Protein expression was evaluated by Western blot (WB) analysis. Neuronal death was scored on the FluoroJadeB stained brain sections harvested 24 h after SE. To assess the effect of SFN on glucose metabolism we have performed a series of 18F-DG μCT/PET recordings 1 h, 1 day, and 3 weeks after the induction of SE. Responses of cerebral blood flow (CBF) to electrical stimulation and their influence by SFN were evaluated by laser Doppler flowmetry (LDF). We have demonstrated that the Nrf2 pathway is upregulated in the CNS of immature rats after SFN treatment. In the animals that had undergone SE, SFN was responsible for lowering glucose uptake in most regions 1 h after the induction of SE. Moreover, SFN partially reversed hypometabolism observed after 24 h and achieved full reversal at approximately 3 weeks after SE. Since no difference in cell death was observed in SFN treated group, these changes cannot be attributed to differences in neurodegeneration. SFN per se did not affect the glucose uptake at any given time point suggesting that SFN improves endogenous CNS ability to adapt to the epileptogenic insult. Furthermore, we had discovered that SFN improves blood flow and accelerates CBF response to electrical stimulation. Our findings suggest that SFN improves metabolic changes induced by SE which have been identified during epileptogenesis in various animal models of acquired epilepsy.

Stem Cell-Derived Extracellular Vesicles as Potential Therapeutic Approach for Acute Kidney Injury.

Acute kidney injury is a frequent complication of hospitalized patients and significantly increases morbidity and mortality, worsening costs and length of hospital stay. Despite this impact on healthcare system, treatment still remains only supportive (dialysis). Stem cell-derived extracellular vesicles are a promising option as they recapitulate stem cells properties, overcoming safety issues related to risks or rejection or aberrant differentiation. A growing body of evidence based on pre-clinical studies suggests that extracellular vesicles may be effective to treat acute kidney injury and to limit fibrosis through direct interference with pathogenic mechanisms of vascular and tubular epithelial cell damage. We herein analyze the state-of-the-art knowledge of therapeutic approaches with stem cell-derived extracellular vesicles for different forms of acute kidney injury (toxic, ischemic or septic) dissecting their cytoprotective, regenerative and immunomodulatory properties. We also analyze the potential impact of extracellular vesicles on the mechanisms of transition from acute kidney injury to chronic kidney disease, with a focus on the pivotal role of the inhibition of complement cascade in this setting. Despite some technical limits, nowadays the development of therapies based on stem cell-derived extracellular vesicles holds promise as a new frontier to limit acute kidney injury onset and progression.

Ameliorative effect of N-acetylcysteine on the testicular tissue of adult male albino rats after glyphosate-based herbicide exposure.

Glyphosate (GLP) is a broad-spectrum herbicide that is frequently used in crop production, but its residues remain in foodstuffs. This, in turn, has led to potential adverse effects on both human and animal health. Recent studies emphasized that GLP induces teratogenic effects and reproductive disorders, but its mechanism of toxicity is highly debated. N-acetylcysteine (NAC) is well known for its potent antioxidant capacity in addition to anti-inflammatory and cytoprotective properties. Therefore, our study aimed to investigate the reproductive toxicity of GLP in mature rats and evaluate the possible ameliorative effect of NAC against this toxicity. To this end, 30 adult male rats were assigned into three groups (10 rats per group) as follows: Group I, negative control; group II, GLP-exposed; 375 mg/kg GLP, orally; group III, NAC-cotreated, 160 mg/kg NAC 1 h before GLP, plus GLP, 375 mg/kg orally for 6 weeks. At the end of the experiment, the testicles were collected for semen analysis and biochemical, histopathological, and immunohistochemical studies. GLP-exposed rats exhibited disturbances in seminal parameters and a significant increase in malondialdehyde levels and expression of apoptotic markers. Several histopathological changes were observed, including strong immunoreactions for caspase-3 and proliferating cell nuclear antigen. Conversely, the administration of NAC before GLP was able to improve seminal parameters, attenuate the induced oxidative stressand apoptosis in addition to the regeneration of testicular damage. In conclusion, NAC can ameliorate the reproductive toxicity induced by GLP to an acceptable degree.

The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities

The National Consensus was prepared with the participation of the National Medical Association for the Study of the Multimorbidity, Russian Scientific Liver Society, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians, National Society for Preventive Cardiology, Professional Foundation for the Promotion of Medicine Fund PROFMEDFORUM. The aim of the multidisciplinary consensus is a detailed analysis of the course of non-alcoholic fatty liver disease (NAFLD) and the main associated conditions. The definition of NAFLD is given, its prevalence is described, methods for diagnosing its components such as steatosis, inflammation and fibrosis are described. The association of NAFLD with a number of cardio-metabolic diseases (arterial hypertension, atherosclerosis, thrombotic complications, type 2 diabetes mellitus, obesity, dyslipidemia, etc.), chronic kidney disease and the risk of developing hepatocellular cancer were analyzed. The review of non-drug methods of treatment of NAFLD and modern opportunities of pharmacotherapy are presented. The possibilities of new molecules in the treatment of NAFLD are considered: agonists of nuclear receptors, antagonists of pro-inflammatory molecules, etc. The positive properties and disadvantages of currently used drugs (vitamin E, thiazolidinediones, etc.) are described. Special attention is paid to the multi-target ursodeoxycholic acid molecule in the complex treatment of NAFLD as a multifactorial disease. Its anti-inflammatory, anti-oxidant and cytoprotective properties, the ability to reduce steatosis an independent risk factor for the development of cardiovascular pathology, reduce inflammation and hepatic fibrosis through the modulation of autophagy are considered. The ability of ursodeoxycholic acid to influence glucose and lipid homeostasis and to have an anticarcinogenic effect has been demonstrated. The Consensus statement has advanced provisions for practitioners to optimize the diagnosis and treatment of NAFLD and related common pathogenetic links of cardio-metabolic diseases.

Correction of intestinal microbial composition disturbances as a potential link in complex therapy of patients with COVID-19

The article reflects the potential for correcting intestinal microbiota disorders in the complex therapy of patients with COVID-19. It has been noted that the inclusion of dietary fiber in the diet contributes to protection against disruption of the integrity of the intestinal barrier and may limit bacterial translocation into the systemic circulation. The possibility of using psyllium (Mucofalk) is reflected, the action of which is realized both through its sorption, cytoprotective and anti-inflammatory properties in viral lesions of the gastrointestinal tract, and through stimulation of the own beneficial intestinal microbiota. The paper presents studies of the prospects for the use of probiotics, synbiotics in the complex therapy of patients with COVID-19. Detailed data are provided on the mechanisms of the positive effect of short-chain fatty acid preparations on reducing the severity of the disease in patients with COVID-19. It was noted that taking the drug Zacofalk leads to a significant increase in its own butyrate-producing microbiota (Faecalibacterium prausnitzii) and suppression of the growth of opportunistic flora with pro-inflammatory activity. The results of a recent study are presented showing that in patients with a mild course of COVID infection with respiratory and intestinal symptoms, the administration of Zakofalk for 30 days (3 tablets per day) led to significantly faster stool normalization (by day 7), persistent normalization of the frequency and consistency of stools by the 21st day and a significantly more pronounced regression of bloating and abdominal pain, as well as a decrease in the risk of developing post-infectious irritable bowel syndrome.

Chemical investigation and screening of anti-cancer potential of Syzygium aromaticum L. bud (clove) essential oil nanoemulsion.

This study was done to improve the medicinal properties of Syzygium Aromaticum L by processing S. Aromaticum L. bud essential oil (SABE) to the Nanoemulsion drug delivery system (SABE-NE) and investigating its anti-tumor and apoptotic impacts against the human HT-29 colon cancer cells. Applying the ultra-sonication method and characterization by DLS and FESEM analysis facilitates the nanoemulsification procedure. Human cancer (HT-29) and normal (HFF) cell lines were then evaluated based on the SABE-NE apoptotic and cytotoxic effects. In an in vitro section, flow cytometry method, Cas3 gene profile, AO/PI cell staining, and MTT assays are used to analyze the apoptotic and cytotoxic activities. In further analysis, liver lipid peroxidation and antioxidant genes expression (SOD, CAT, and GPx) investigate alterations in mice organs. As a result, produced 131.2nm SABE-NE induces apoptosis response and cellular death (Cas3 up-regulation and enhanced SubG1 peaks). Subsequently, the HT-29 cells' viability can reduce significantly, while HFF cells indicate confined cytotoxic impacts. Moreover, in vivo test results on mice livers demonstrate the cytoprotective properties of SABE-NE (reduced lipid peroxidation and increased antioxidant enzymes gene expression and nondetectable cytotoxic impacts). We produced a novel nanoemulsion drug delivery system called SABE-NE, a cell-specific apoptotic inducer. We thus can be utilized as an efficient anti-cancer compound for human colon cancer treatment. However, further supplementary studies are required to verify and approve its cell-specific anti-tumor activity.

Benefits and adverse events of melatonin use in the elderly (Review).

Melatonin is a hormone secreted by the pineal gland in accordance with the circadian rhythm when the light level decreases. Reduction of melatonin secretion with age may be associated with physiological aging in neurodegenerative diseases by affecting the suprachiasmatic nucleus or of the neuronal pathways of transmission to the pineal gland. A significant decrease in melatonin synthesis has been reported in various disorders and diseases, including cardiovascular diseases, metabolic disorders (particularly diabetes type 2), cancer and endocrine diseases. In addition to the fact, that melatonin is a sleep inducer, it also exerts cytoprotective properties as an antioxidant and free radical scavenger. The therapeutic role of melatonin has been demonstrated in sleep disorders, eye damage and cardiovascular disease. The association between melatonin and β-blockers has had a positive impact on sleep disorders in clinical trials. Previous studies have reported the anti-inflammatory effect of melatonin by adjusting levels of pro-inflammatory cytokines, including interleukin (IL)-6, IL-1β and tumor necrosis factor-α. Melatonin treatment has been demonstrated to decrease IL-6 and IL-10 expression levels and efficiently attenuate T-cell proliferation. Currently, there is an inconsistency of scientific data regarding the lowest optimal dose and safety of melatonin for long-term use. The aim of the present review was to summarize the evidence on the role of melatonin in various clinical conditions and highlight the future research in this area.

Features of therapeutic correction of GERD: focus on cytoprotection (with a clinical case)

Тo date, the possible links of the pathogenesis of this disease have been well studied and described, which predetermine certain approaches to the treatment of various variants of gastroesophageal reflux disease (GERD). Effective drug therapy for GERD includes proton pump inhibitors (PPI). However, PPI monotherapy is not always effective. One approach is to increase the PPI dose. At the same time, combination therapy with the addition of drugs that affect the protective properties of the esophageal mucosa seems to be more rational. It is known that in the development of GERD, the violation of cytoprotection of the esophageal mucosa is one of the key links in pathogenesis. Consequently, the issue of combination therapy of PPIs with drugs that increase the protective properties of the mucous barrier along with acid suppression becomes relevant. An example of such an approach is the appointment of rebamipide, the action of which is to regulate the synthesis of prostaglandins through COX-2 mediated mechanisms, influence on endothelial growth factor, increase the expression of tight intercellular contact proteins in epithelial cells of the mucous membrane, reduce the level of interleukin-8 and free oxygen radicals, directed to protect the mucous membrane of the gastrointestinal tract and restore its natural barrier properties. The effectiveness of the combination of PPI and rebamipide contributes to a greater regression of complaints in patients with GERD and a lower frequency of disease relapses than with PPI monotherapy. This article provides a review of the literature on the features of GERD therapy, primarily with an emphasis on the correction of the cytoprotective properties of the esophageal mucosa, including against the background of the use of nonsteroidal anti-inflammatory drugs (NSAID), and a clinical case analysis with a discussion of rational pharmacological correction.

Macroscopic assessment of protective effect of cryopreserved placenta extract in ibuprofen-induced gastroenterocolonopathy

Background. Over-the-counter use of nonsteroidal anti-inflammatory drugs leads to their uncontrolled consumption among the population, which in some cases makes it impossible to prevent and timely detect adverse drug effects, and their effectiveness does not always satisfy clinicians. The purpose was to characterize the cytoprotective properties of cryopreserved placenta extract according to the condition of the mucous membrane of the proximal (esophagus and stomach) and distal (small and large intestine) parts of the gastrointestinal tract on the model of ibuprofen-induced esophagogastroenterocolonopathy. Materials and methods. In vivo experimental studies were performed on 28 male rats. Subchronic ibuprofen-induced gastrointestinal lesions were reproduced by intragastric administration of ibuprofen to rats at a dose of 310 mg/kg. The condition of the gastrointestinal tract mucous membrane was assessed macroscopically on a scale. Results. The therapeutic and prophylactic efficacy of esomeprazole statistically significantly (р < 0.05) took place in the proximal parts of the gastrointestinal tract but had little effect on the prevalence of ulcerative lesions in the intestine. At the same time, unlike esomeprazole, which is known to have only gastroprotective activity, cryopreserved placenta extract had a cytoprotective effect both in the stomach and in the distal parts of the gastrointestinal tract — small and large intestine. Thus, the prevalence of ibuprofen-induced both entero- and colonopathy on the background of the study of the extract was almost twice lower than in rats that did not receive correction drugs. Conclusions. It is established that the use of cryopreserved placenta extract in the treatment-and-prophylactic mode has comparable to esomeprazole gastroprotective activity. In addition, it was found that the use of the studied cryoextract was accompanied by a decrease in the multiplicity of ulcerative defects in the small and large intestine of rats, by 4.6 and 3.8 times, respectively, compared to the control animals.

Luteoloside protects the vascular endothelium against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway.

Iron overload injury is considered to be a part of blood stasis syndrome of arthralgia in traditional Chinese medicine. Its primary therapies include clearing heat and detoxification, activating blood circulation, and removing blood stasis. Lonicera japonica flos (LJF) has long been known as an excellent antipyretic and antidote. Luteoloside (Lut) is one of the main components of LJF and exhibits antioxidant, anti-inflammatory, and cytoprotective properties. However, the protection of Lut against iron overload injury and its underlying mechanisms remain unclear. Therefore, HUVECs were exposed to 50 μmol·L-1 iron dextran for 48 h to establish an iron overload damage model and the effects of Lut were assessed. Our results showed that 20 μmol·L-1 Lut not only increased cell viability and weakened LDH activity, but also significantly up-regulated DDAHⅡ expression and activity, increased p-eNOS/eNOS ratio and NO content, and reduced ADMA content in HUVECs exposed to iron overload. Furthermore, Lut significantly attenuated intracellular/mitochondrial ROS generation, improved SOD, CAT, and GSH-Px activities, reduced MDA content, maintained MMP, inhibited mPTP opening, prevented cyt c from mitochondria released into cytoplasm, reduced cleaved-caspase3 expression, and ultimately decreased cell apoptosis induced by iron overload. The effects of Lut were similar to those of L-arginine (an ADMA competitive substrate), cyclosporin A (a mPTP blocker agent), and edaravone (a free radical scavenger) as positive controls. However, addition of pAD/DDAH II-shRNA adenovirus reversed the above beneficial effects of Lut. In conclusion, Lut can protect HUVECs against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway. The mitochondria are the target organelles of Lut's protective effects.

Profiles of Fatty Acids, Polyphenols, Sterols, and Tocopherols and Scavenging Property of Mediterranean Oils: New Sources of Dietary Nutrients for the Prevention of Age-related Diseases.

The present study provides the fatty acid, tocopherol, phytosterol, and polyphenol profiles of some Mediterranean oils extracted from pumpkin, melon, and black cumin seed oils and those of dietary argan seed oil. Gas chromatography analysis revealed that oleic and linoleic acids were the most abundant fatty acids. Argan and melon seed oils exhibited the highest levels of oleic acid (47.32±0.02%) and linoleic acid (58.35±0.26%), respectively. In terms of tocopherols, melon seed oil showed the highest amount (652.1±3.26 mg/kg) with a predominance of γ-tocopherol (633.1±18.81 mg/kg). The phytosterol content varied between 2237.00±37.55 µg/g for argan oil to 6995.55±224.01 µg/g for melon seed oil. High Performance Liquid Chromatography analysis also revealed the presence of several polyphenols: vanillin (0.59 mg equivalents Quercetin/100 g) for melon seed oil, and p-hydroxycinnamic acid (0.04 mg equivalents Quercetin/100 g), coumarine (0.05 mg equivalents Quercetin/100 g), and thymoquinone (1.2 mg equivalents Quercetin/100 g) for black cumin seed oil. The "Kit Radicaux Libres" (KRL) assay used to evaluate the scavenging properties of the oils showed that black cumin seed oil was the most efficient. On the light of the richness of all Mediterranean oil samples in bioactive compounds, the seed oils studied can be considered as important sources of nutrients endowed with cytoprotective properties which benefits in preventing age-related diseases which are characterized by an enhanced oxidative stress.

In vivo evaluation of the potential protective effects of prolactin against damage caused by methylmercury.

Non-biodegradable metals such as mercury accumulate in living organisms during life (bioaccumulation) and also within trophic webs (biomagnification) and may reach high concentrations in humans. The contamination of humans by mercury in drinking water and food may be common, in particular in riverside communities that have a diet rich in fish. In vitro studies of human cell lines exposed to the cytotoxic and mutagenic effects of methylmercury have shown that prolactin has potential cytoprotective properties and may act as a co-mitogenic factor and inhibitor of apoptosis. The present in vivo study investigated the protective potential of prolactin against the toxic effects of methylmercury in the mammal Mus musculus. Histological and biochemical analyses, together with biomarker of genotoxicity, were used to verify the protective potential of prolactin in mice exposed to methylmercury. The reduction in kidney and liver tissue damage was not significant. However, results of biochemical and genotoxic analyses were excellent. After prolactin treatment, a significant reduction was observed in biochemical parameters and mutagenic effects of methylmercury. The study results therefore indicated that prolactin has protective effects against the toxicity of methylmercury and allowed us to suggest the continuation of research to propose prolactin in the future, as an alternative to prevent the damage caused by mercury, especially in populations that are more exposed.

Mechanisms of autophagy regulation by adiponectin

Adiponectin is a multifunctional adipocytokine produced predominantly by adipocytes, with potent antiinflammatory, insulin-sensitizing, and cytoprotective properties. Autophagy is a lysosome-dependent self-degradative process that mediates the degradation of damaged organelles, invading pathogens and protein aggregates, thus maintaining cellular homeostasis. Adiponectin performs different biological functions by regulating autophagy. This review attempts to elucidate the biological responses and potential mechanisms underlying adiponectin-induced autophagy, with an aim to guide the identification of new therapeutic targets of related diseases. Keywords: Adiponectin, adiponectin receptors, autophagy

Bhallataka Rasayana: A Boon in Cancer Treatment

Bhallataka (Semecarpus Anacardium) is one of the Rasayana drugs mentioned in Ayurveda. Semecarpus Anacardium plant belongs to the family Anacardiaceae having allergic expressions as contact dermatitis which originates the fear about use in mind but in Ayurveda it have been used since tradition in various diseased conditions like wounds, piles, uncontrolled cell growth, abdominal lumps etc. Despite these conditions it is more likely used as Rasayana for diseased free long life. Rasayana medicines help in rejuvenating the cells and tissues with antioxidant and cyto-protective properties. In Vitro effects of Semecarpus Anacardium extracts Bhallataka has been evaluated pharmacologically on the isolated tissues and the whole animal. The therapeutic effects of the extract are due to its chemical constituents as phenols, glycosides and lipids mainly. The review supports the information on the use of Semecarpus Anacardium extracts in different cancer conditions.

АЦЕТИЛЦИСТЕИН: БИОЛОГИЧЕСКАЯ АКТИВНОСТЬ И ПОТЕНЦИАЛЬНЫЕ ТЕРАПЕВТИЧЕСКИЕ ВОЗМОЖНОСТИ ПРИМЕНЕНИЯ В КЛИНИКЕ

Objective. To perform an extended analysis of literature sources and evaluate biological activities, bioavailability of acetylcysteine and its potential to correct oxidative stress and inflammatory response in miscellaneous pathological conditions and diseases in clinical setting, as well as to assess the effectiveness of its parenteral application in experimental immunogenic uveitis. Material and Methods. Multiple sources of foreign and home literature concerning the problem of oxidative stress and antioxidant protection system, acetylcysteine (NAC) and its biological actions, ability to restore the pool of intracellular glutathione, its perspective use in miscellaneous pathological conditions, including degenerative and inflammatory diseases of the organ of vision were analyzed. Results. NAC is currently one of the most promising and safe pharmacological substances, which can be used for oxidative stress correction in inflammatory diseases, accompanied by glutathione level depletion. NAC possesses antioxidant, anti-inflammatory, immunomodulatory, antimicrobial, antiviral, detoxifying, cytoprotective and anticarcinogenic properties. Its antioxidant effect is conducted through direct and indirect mechanisms. The indirect antioxidant effect of NAC is realized by replenishing the intracellular pool of glutathione. Conclusions. NAC solves the major problem of intracellular delivery of cysteine as a limiting amino acid for the glutathione synthesis. NAC possesses multi-vector, multidirectional effects and influences on the transcription factors responsible for the development of inflammation, cell proliferation, apoptosis, and maintenance of redox homeostasis in the body. Currently NAC is one of the most promising pharmacological agents for the oxidative stress correction in diseases accompanied by intracellular glutathione depletion.

Antioxidant and Cytoprotective Properties of Polyphenol-Rich Extracts from Antirhea borbonica and Doratoxylon apetalum against Atherogenic Lipids in Human Endothelial Cells.

The endothelial integrity is the cornerstone of the atherogenic process. Low-density lipoprotein (LDL) oxidation occurring within atheromatous plaques leads to deleterious vascular effects including endothelial cell cytotoxicity. The aim of this study was to evaluate the vascular antioxidant and cytoprotective effects of polyphenol-rich extracts from two medicinal plants from the Reunion Island: Antirhea borbonica (A. borbonica), Doratoxylon apetalum (D. apetalum). The polyphenol-rich extracts were obtained after dissolving each dry plant powder in an aqueous acetonic solution. Quantification of polyphenol content was achieved by the Folin–Ciocalteu assay and total phenol content was expressed as g gallic acid equivalent/100 g plant powder (GAE). Human vascular endothelial cells were incubated with increasing concentrations of polyphenols (1–50 µM GAE) before stimulation with oxidized low-density lipoproteins (oxLDLs). LDL oxidation was assessed by quantification of hydroperoxides and thiobarbituric acid reactive substances (TBARS). Intracellular oxidative stress and antioxidant activity (catalase and superoxide dismutase) were measured after stimulation with oxLDLs. Cell viability and apoptosis were quantified using different assays (MTT, Annexin V staining, cytochrome C release, caspase 3 activation and TUNEL test). A. borbonica and D. apetalum displayed high levels of polyphenols and limited LDL oxidation as well as oxLDL-induced intracellular oxidative stress in endothelial cells. Polyphenol extracts of A. borbonica and D. apetalum exerted a protective effect against oxLDL-induced cell apoptosis in a dose-dependent manner (10, 25, and 50 µM GAE) similar to that observed for curcumin, used as positive control. All together, these results showed significant antioxidant and antiapoptotic properties for two plants of the Reunion Island pharmacopeia, A. borbonica and D. apetalum, suggesting their therapeutic potential to prevent cardiovascular diseases by limiting LDL oxidation and protecting the endothelium.

Recombinant Human Soluble Thrombomodulin Suppresses Arteritis in a Mouse Model of Kawasaki Disease

Introduction and Objective: Kawasaki disease (KD) is associated with diffuse and systemic vasculitis of unknown aetiology and primarily affects infants and children. Intravenous immunoglobulin (IVIG) treatment reduces the risk of developing coronary aneurysms, but some children have IVIG-resistant KD, which increases their risk of developing coronary artery injury. Here, we investigated the effect of recombinant human soluble thrombomodulin (rTM), which has anticoagulant, anti-inflammatory, and cytoprotective properties on the development of coronary arteritis in a mouse model of vasculitis. Methods: An animal model of KD-like vasculitis was created by injecting mice with Candida albicans water-soluble fraction (CAWS). This model was used to investigate the mRNA expression of interleukin (IL)-10, tumour necrosis factor alpha (TNF-α), and tissue factor (TF), in addition to histopathology of heart tissues. Results: rTM treatment significantly reduces cardiac vascular endothelium hypertrophy by 34 days after CAWS treatment. In addition, mRNA expression analysis revealed that rTM administration increased cardiac IL-10 expression until day 27, whereas expression of TNF-α was unaffected. Moreover, in the spleen, rTM treatment restores IL-10 and TF expression to normal levels. Conclusion: These findings suggest that rTM suppresses CAWS-induced vasculitis by upregulating IL-10. Therefore, rTM may be an effective treatment for KD.

Exploring the translational potential of clusterin as a biomarker of early osteoarthritis.

BackgroundClusterin (CLU; also known as apolipoprotein J) is an ATP-independent holdase chaperone that prevents proteotoxicity as a consequence of protein aggregation. It is a ∼60 kDa disulfide-linked heterodimeric protein involved in the clearance of cellular debris and the regulation of apoptosis. CLU has been proposed to protect cells from cytolysis by complement components and has been implicated in Alzheimer’s disease due to its ability to bind amyloid-β peptides and prevent aggregate formation in the brain. Recent studies suggest that CLU performs moonlighting functions. CLU exists in two major forms: an intracellular form and a secreted extracellular form. The intracellular form of CLU may suppress stress-induced apoptosis by forming complexes with misfolded proteins and facilitates their degradation. The secreted form of CLU functions as an extracellular chaperone that prevents protein aggregation.MethodsIn this review, we discuss the published literature on the biology of CLU in cartilage, chondrocytes, and other synovial joint tissues. We also review clinical studies that have examined the potential for using this protein as a biomarker in synovial and systemic fluids of patients with rheumatoid arthritis (RA) or osteoarthritis (OA).ResultsSince CLU functions as an extracellular chaperone, we propose that it may be involved in cytoprotective functions in osteoarticular tissues. The secreted form of CLU can be measured in synovial and systemic fluids and may have translational potential as a biomarker of early repair responses in OA.ConclusionThere is significant potential for investigating synovial and systemic CLU as biomarkers of OA. Future translational and clinical orthopaedic studies should carefully consider the diverse roles of this protein and its involvement in other comorbidities. Therefore, future biomarker studies should not correlate circulating CLU levels exclusively to the process of OA pathogenesis and progression. Special attention should be paid to CLU levels in synovial fluid.The Translational potential of this articleThere is significant potential for investigating synovial and systemic CLU as a predictive biomarker of osteoarthritis (OA) progression and response to novel treatments and interventions. Given that CLU plays diverse roles in other comorbidities such as rheumatoid arthritis (RA) and obesity, future translational and clinical orthopaedic biomarker studies should not directly correlate circulating CLU levels to the process of OA pathogenesis and progression. However, special attention should be paid to CLU levels in synovial fluid. The cytoprotective properties of CLU may support the implementation of regenerative strategies and new approaches for developing targeted therapeutics for OA.

Prospects for using molecular hydrogen in environmental and sport medicine (literature review)

The relevance of research on molecular hydrogen in the world has increased significantly, since it turned out to be an extremely unique reagent, since it has the ability to act at the cellular level. Hydrogen is able to cross the blood-brain barrier, penetrate into mitochondria and other areas of cells, where it exhibits antioxidant, anti-apoptotic, anti-inflammatory and cytoprotective properties. The aim of the scientific review is to theoretically substantiate the current state of the use of molecular hydrogen and hydrogen water in environmentally friendly and sports medicine. For this, evidence has been provided regarding the effect of consumption of molecular hydrogen and hydrogen water on changes in physiological and biochemical parameters, taking into account the oxidative stress caused by exercise. In addition, this review highlights possible future directions in this area of research.