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A growing body of biomedical literature suggests a bidirectional regulatory relationship between cardiac calcium (Ca2+)-regulating proteins and reactive oxygen species (ROS) that is integral to the pathogenesis of various cardiac disorders via oxidative stress (OS) signaling. To address the challenge of finding hidden connections within the growing volume of biomedical research, we developed a data science pipeline for efficient data extraction, transformation, and loading. Employing the CaseOLAP (Context-Aware Semantic Analytic Processing) algorithm, our pipeline quantifies interactions between 128 human cardiomyocyte Ca2+-regulating proteins and eight cardiovascular disease (CVD) categories. Our machine-learning analysis of CaseOLAP scores reveals that the molecular interfaces of Ca2+-regulating proteins uniquely associate with cardiac arrhythmias and diseases of the cardiac conduction system, distinguishing them from other CVDs. Additionally, a knowledge graph analysis identified 59 of the 128 Ca2+-regulating proteins as involved in OS-related cardiac diseases, with cardiomyopathy emerging as the predominant category. By leveraging a link prediction algorithm, our research illuminates the interactions between Ca2+-regulating proteins, OS, and CVDs. The insights gained from our study provide a deeper understanding of the molecular interplay between cardiac ROS and Ca2+-regulating proteins in the context of CVDs. Such an understanding is essential for the innovation and development of targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

In this study, we investigated the protective effects of astaxanthin (AST) against oxidative stress induced by the combination of azoxymethane (AOM) and dextran sulfate sodium (DSS) in colitis-associated cancer (CAC) and TNF-α-induced human colorectal cancer cells (SW480), as well as the underlying mechanism. In vitro experiments revealed that astaxanthin reduced reactive oxygen species (ROS) generation and inhibited the expression of Phosphorylated JNK (P-JNK), Phosphorylated ERK (P-ERK), Phosphorylated p65 (P-p65), and the NF-κB downstream protein cyclooxygenase-2 (COX-2). In vivo experiments showed that astaxanthin ameliorated AOM/DSS-induced weight loss, shortened the colon length, and caused histomorphological changes. In addition, astaxanthin suppressed cellular inflammation by modulating the MAPK and NF-κB pathways and inhibiting the expression of the proinflammatory cytokines IL-6, IL-1β, and TNF-α. In conclusion, astaxanthin attenuates cellular inflammation and CAC through its antioxidant effects. [ABSTRACT FROM AUTHOR]

Background: Tobacco smoking is the leading cause of preventable death and disease worldwide, with over 8 million annual deaths attributed to cigarette smoking. This study investigates the impact of cigarette smoke and heated tobacco products (HTPs) on microglial function, focusing on toxicological profiles, inflammatory responses, and oxidative stress using ISO standard and clinically relevant conditions of exposure. Methods: We assessed cell viability, reactive oxygen species (ROS) production, lipid peroxidation, mitochondrial function, unfolded protein response, and inflammation in human microglial cells (HMC3) exposed to cigarette smoke, HTP aerosol or nicotine. Results: Our findings show that cigarette smoke significantly reduces microglial viability, increases ROS formation, induces lipid peroxidation, and reduces intracellular glutathione levels. Cigarette smoke also alters the expression of genes involved in mitochondrial dynamics and biogenesis, leading to mitochondrial dysfunction. Additionally, cigarette smoke impairs the unfolded protein response, activates the NF-κB pathway, and induces a pro-inflammatory state characterized by increased TNF and IL-18 expression. Furthermore, cigarette smoke causes DNA damage and decreases the expression of the aging marker Klotho β. In contrast, HTP, exhibited a lesser degree of microglial toxicity, with reduced ROS production, lipid peroxidation, and mitochondrial dysfunction compared to conventional cigarettes. Conclusion: These results highlight the differential toxicological profile of cigarette smoke and HTP on microglial cells, suggesting a potential harm reduction strategy for neurodegenerative disease for smokers unwilling or unable to quit. [ABSTRACT FROM AUTHOR]

Lepidium meyenii Walp (LmW) or Maca, including its bioactive components such as macamides, among others, has demonstrated antioxidant effects. However, the effect size (ES) of LmW on oxidative stress has not been qualitatively described and calculated. The primary objective of this systematic review and meta-analysis was to review and qualitatively describe the studies published up to 2023 that supplemented LmW to control cellular oxidative stress; the secondary objective was to calculate the ES of the different interventions. The search was designed following the PRISMA® guidelines for systematic reviews and meta-analyses and performed in the Web of Science, Scopus, SPORTDiscus, PubMed, and MEDLINE until 2023. The selection of studies included randomized controlled trials, with tests and post-tests, both in vitro and in vivo in animals and humans. The methodological quality and risk of bias were evaluated with the CAMARADES tool. The main variables were reduced glutathione, glutathione peroxidase, superoxide dismutase, and malondialdehyde. The analysis was conducted with a pooled standardized mean difference (SMD) through Hedges' g test (95% CI). Eleven studies were included in the systematic review and eight in the meta-analysis. They revealed a small effect for reduced glutathione (SMD = 0.89), a large effect for glutathione peroxidase (SMD = 0.96), a moderate effect for superoxide dismutase (SMD = 0.68), and a moderate effect for malondialdehyde (SMD = −0.53). According to the results, the phytochemical compounds of LmW effectively controlled cellular oxidative stress, mainly macamides. It was also determined that a higher dose of LmW generated a greater antioxidant effect. However, information concerning humans is scarce. [ABSTRACT FROM AUTHOR]

This in vivo study performed in rat adjuvant arthritis aims to advance the understanding of astaxanthin's therapeutic properties for the possible treatment of rheumatoid arthritis (RA) in monotherapy and along with the standard RA treatment, methotrexate (MTX), in combination therapy. The main goal was to elucidate astaxanthin's full therapeutic potential, evaluate its dose dependency, and compare its effects in monotherapy with other carotenoids such as β-carotene and β-cryptoxanthin (KXAN). Moreover, potential differences in therapeutic activity caused by using different sources of astaxanthin, synthetic (ASYN) versus isolated from Blakeslea trispora (ASTAP), were evaluated using one-way ANOVA (Tukey-Kramer post hoc test). KXAN was the most effective in reducing plasma MMP-9 levels in monotherapy, significantly better than MTX, and in reducing hind paw swelling. The differences in the action of ASTAP and ASYN have been observed across various biometric, anti-inflammatory, and antioxidative parameters. In combined therapy with MTX, the ASYN + MTX combination proved to be better. These findings, especially the significant anti-arthritic effect of KXAN and ASYN + MTX, could be the basis for further preclinical studies. [ABSTRACT FROM AUTHOR]

Ischemia/reperfusion injury (IRI) represents a significant contributor to morbidity and mortality associated with various clinical conditions, including acute coronary syndrome, stroke, and organ transplantation. During ischemia, a profound hypoxic insult develops, resulting in cellular dysfunction and tissue damage. Paradoxically, reperfusion can exacerbate this injury through the generation of reactive oxygen species and the induction of inflammatory cascades. The extensive clinical sequelae of IRI necessitate the development of therapeutic strategies to mitigate its deleterious effects. This has become a cornerstone of ongoing research efforts in both basic and translational science. This review examines the use of molecular hydrogen for IRI in different organs and explores the underlying mechanisms of its action. Molecular hydrogen is a selective antioxidant with anti-inflammatory, cytoprotective, and signal-modulatory properties. It has been shown to be effective at mitigating IRI in different models, including heart failure, cerebral stroke, transplantation, and surgical interventions. Hydrogen reduces IRI via different mechanisms, like the suppression of oxidative stress and inflammation, the enhancement of ATP production, decreasing calcium overload, regulating cell death, etc. Further research is still needed to integrate the use of molecular hydrogen into clinical practice. [ABSTRACT FROM AUTHOR]

Astaxanthin, a potent antioxidant found in marine organisms such as microalgae and krill, may offer ergogenic benefits to endurance athletes. Originally used in fish feed, astaxanthin has shown a greater ability to mitigate various reactive oxygen species and maintain the structural integrity of mitochondria compared to other exogenous antioxidants. More recent work has shown that astaxanthin may improve: (1) cycling time trial performance, (2) cardiorespiratory measures such as submaximal heart rate during running or cycling, (3) recovery from delayed-onset muscle soreness, and (4) endogenous antioxidant capacity such as whole blood glutathione within trained populations. In this review, the history of astaxanthin and its chemical structure are first outlined before briefly describing the various adaptations (e.g., mitochondrial biogenesis, enhanced endogenous antioxidant capacity, etc.) which take place specifically at the mitochondrial level as a result of chronic endurance training. The review then concludes with the potential additive effects that astaxanthin may offer in conjunction with endurance training for the endurance athlete and offers some suggested practical recommendations for athletes and coaches interested in supplementing with astaxanthin. [ABSTRACT FROM AUTHOR]

Obesity alters lipid profile, blood glucose, liver enzymes, oxidative stress, and hormonal balance. Fennel has shown anti-obesity effects in preliminary studies, but its role in ameliorative metabolic complications of obesity needs further research. This study assessed the provisional influences of fennel extract against high-fat diet-provoked metabolic deviations in rats. Forty male albino rats were allocated into standard diet control, obese control, low dose fennel (100 mg/kg) and high dose fennel (300 mg/kg) groups. Obesity was triggered by 4 weeks of high-fat nourishment. Fennel extract was applied orally for 6 weeks. Parameters considered were body weight, lipid profile, blood glucose, liver enzymes, antioxidant status, thyroid hormones, leptin, and hepatic insulin receptor gene expression. Fennel significantly diminished body weight, total cholesterol, triglycerides, LDL-cholesterol, liver enzymes, glucose, and leptin while increasing HDL-cholesterol, antioxidant enzymes, and thyroid stimulating hormone compared to obese controls. Histological examination has shown alleviation of fat accumulation and intracellular changes in the liver. Insulin receptor gene expression was also significantly increased by fennel extract. This study demonstrated that fennel extract reverses obesity-induced metabolic syndrome, oxidative stress, endocrine disruption, and histopathological change in the liver of rats. The hypolipidemic, hypoglycemic, antioxidant, and hepatoprotective properties of fennel may be beneficial in managing obesity-associated metabolic complications. [ABSTRACT FROM AUTHOR]

Bilobalide has shown strong anti-inflammatory activity. Colorectal cancer (CRC) is closely associated with inflammation. However, no studies have reported on the use of bilobalide for treating CRC. This study aims to evaluate the effect of bilobalide on CRC prevention. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (RT-qPCR), Western blotting, and immunofluorescence showed that bilobalide significantly inhibits the M2 polarization of macrophages dependent on phorbol 12-myristate 13-acetate (PMA) and interleukin-4 (IL-4). Analysis of signaling pathways showed that the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and signal transducer and activator of transcription 3 (STAT3) was regulated. In particular, human CRC organoids were established. Western blotting, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL), and analysis of cell viability and morphology further supported the hypothesis that the anti-CRC effects of bilobalide could be explained by its ability to suppress M2 macrophage polarization and promote M1 transformation. C57BL/6 mice treated with azoxymethane (AOM)/dextran sodium sulfate (DSS) were divided into three groups, i.e., control, AOM/DSS, low (2.5 mg/kg), and high (5 mg/kg). High-dose bilobalide markedly inhibited the progression of CRC, as evidenced by the increased body weight, decrease in disease activity index (DAI) death rate, and alleviation of colon length reduction and tumorigenesis. According to the in vivo results, reduced levels of inflammatory cytokines in the serum included tumor necrosis factor (TNF-α), IL-6, IL-1β, and IL-10. Bilobalide reduced oxidative stress indices, lipid peroxide (LPO), and malondialdehyde (MDA) and increased reduced glutathione (GSH). In addition, the expression of proliferating cell nuclear antigen (PCNA), Ki67, cellular Myc (c-Myc), and CD206 was downregulated in the drug-treated groups, as confirmed by the immunohistochemical staining. Collectively, these results indicated that bilobalide administration improve experimental CRC by inhibiting M2 macrophage polarization and oxidative stress. Thus, bilobalide may prevent CRC and serve as a potential therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

This study investigated the effects of 6 mg/day of astaxanthin supplementation on markers of oxidative stress and substrate metabolism during a graded exercise test in active young men. A double-blind, randomized, counterbalanced, cross-over design was used. Fourteen men (age = 23 * 2 years) supplemented with 6 mg/day ofastaxanthin and a placebo for4 weeks, with a 1 week washout period between treatments. Following each supplementation period, a fasting blood sample was obtained to measure markers of oxidative stress: glutathione, hydrogen peroxide, advanced oxidation protein products, and malondialdehyde. Participants also completed a graded exercise test after each treatment to determine substrate utilization during exercise at increasing levels of intensity. Glutathione was -7% higher following astaxanthin compared with placebo (1,233 * 133 vs. 1,156 + 185 ILM, respectively; p =.02, d = 0.48). Plasma hydrogen peroxide and malondialdehyde were not different between treatments (p > .05). Although not statistically significant (p = .45), advanced oxidation protein products were reduced by -28%. During the graded exercise test, mean fat oxidation rates were not different between treatments (p > .05); however, fat oxidation decreased from 50 to 120 W (p <.001) and from 85 to 120 W (p =.004) in both conditions. Astaxanthin supplementation of 6 mg/day for 4 weeks increased whole blood levels of the antioxidant glutathione in active young men but did not affect oxidative stress markers or substrate utilization during exercise. Astaxanthin appears to be an effective agent to increase endogenous antioxidant status. [ABSTRACT FROM AUTHOR]

Oxidative stress is a deteriorating condition that arises due to an imbalance between the reactive oxygen species and the antioxidant system or defense of the body. The key reasons for the development of such conditions are malfunctioning of various cell organelles, such as mitochondria, endoplasmic reticulum, and Golgi complex, as well as physical and mental disturbances. The nervous system has a relatively high utilization of oxygen, thus making it particularly vulnerable to oxidative stress, which eventually leads to neuronal atrophy and death. This advances the development of neuroinflammation and neurodegeneration-associated disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, dementia, and other memory disorders. It is imperative to treat such conditions as early as possible before they worsen and progress to irreversible damage. Oxidative damage can be negated by two mechanisms: improving the cellular defense system or providing exogenous antioxidants. Natural antioxidants can normally handle such oxidative stress, but they have limited efficacy. The valuable features of nanoparticles and/or nanomaterials, in combination with antioxidant features, offer innovative nanotheranostic tools as potential therapeutic modalities. Hence, this review aims to represent novel therapeutic approaches like utilizing nanoparticles with antioxidant properties and nanotheranostics as delivery systems for potential therapeutic applications in various neuroinflammation- and neurodegeneration-associated disease conditions. [ABSTRACT FROM AUTHOR]

As diabetes rates surge globally, there is a corresponding rise in the number of patients suffering from diabetic kidney disease (DKD), a common complication of diabetes. DKD is a significant contributor to chronic kidney disease, often leading to end-stage renal failure. However, the effectiveness of current medical treatments for DKD leaves much to be desired. Molecular hydrogen (H2) is an antioxidant that selectively reduces hydroxyl radicals, a reactive oxygen species with a very potent oxidative capacity. Recent studies have demonstrated that H2 not only possesses antioxidant properties but also exhibits anti-inflammatory effects, regulates cell lethality, and modulates signal transduction. Consequently, it is now being utilized in clinical applications. Many factors contribute to the onset and progression of DKD, with mitochondrial dysfunction, oxidative stress, and inflammation being strongly implicated. Recent preclinical and clinical trials reported that substances with antioxidant properties may slow the progression of DKD. Hence, we undertook a comprehensive review of the literature focusing on animal models and human clinical trials where H2 demonstrated effectiveness against a variety of renal diseases. The collective evidence from this literature review, along with our previous findings, suggests that H2 may have therapeutic benefits for patients with DKD by enhancing mitochondrial function. To substantiate these findings, future large-scale clinical studies are needed. [ABSTRACT FROM AUTHOR]

The reactive oxygen species (ROS) signaling in the hypothalamus is crucial for energy homeostasis; however, excessive ROS exacerbates oxidative stress and promotes hypothalamic dysfunctioning. Also, the emergence of insulin insensitivity and obesity are directly linked to hypothalamic disturbance. The objective of the present study was to determine the effectiveness of gallic acid (GA) as a therapeutic agent against long-term exposure to a high-fat diet (HFD) on the antioxidant profile in the hypothalamus in correlation with glucose tolerance, insulin resistance, and inflammatory parameters. For the current study total of 24 female Swiss-albino mice were divided into 4 groups, 6 animals each for the duration of 90 days. Group I control, group II HFD, group III HFD + GA (50 mg/kg b. wt orally), and group IV GA (50 mg/kg b. wt orally). At the end of the experiment, biochemical, antioxidative, inflammatory, and histological parameters were assessed. Although there was no change in daily food consumption, the administration of GA in HFD-treated mice resulted in a notable reduction in body weight (p ≤ 0.001) and improved hypothalamic superoxide dismutase (SOD) (p = 0.019), catalase (CAT) (p ≤ 0.001), and glutathione peroxidase (GPx) (p ≤ 0.001) in the HFD-treated group. The administration of GA has reduced (p ≤ 0.001) serum glucose, cholesterol, and triglyceride and increased (p ≤ 0.001) high-density lipoprotein (HDL) levels. Moreover, HFD group for 90 days exhibited a decreased tolerance to a 2-h intraperitoneal glucose tolerance test (GTT). GA has substantially reduced (p ≤ 0.001) insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and serum interleukin (IL)-6 in HFD-treated females. The results emphasize that GA can improve the hypothalamic antioxidative profile and insulin sensitivity along with glucose and lipid metabolism in progressive obesity. Figure depicting the role of gallic acid against hypothalamic oxidative stress, insulin resistance, increased inflammatory marker, dyslipidemia, and diminished glucose tolerance caused by a high-fat diet. Symbol used:→ indicate increase and ↛ indicate suppression of activity. [ABSTRACT FROM AUTHOR]

It is well documented that exercise-induced muscle damage (EIMD) decreases exercise performance by elevated inflammation and subjective discomfort. Due to its potent antioxidative properties, astaxanthin (AX) may serve as a potential dietary supplement strategy for mitigating delayed-onset muscle soreness (DOMS) and enhancing recovery and performance. This study aimed to investigate the effects of AX on markers of muscle damage, inflammation, DOMS, and anaerobic performance and substrate metabolism. Thirteen resistance-trained men (mean ± SD, age, 23.4 ± 2.1 years) completed a double-blind, counterbalanced, and crossover design with a 1-week washout period between 2, 4-week supplementation periods at 12 mg·d-1 of AX or placebo. After each supplementation period, subjects completed 2 trials, with trial 1 including a graded exercise test (GXT) and a 30-second Wingate and trial 2 including an EIMD protocol followed by the collection of fasting blood samples (pre-post) to measure creatine kinase, advanced oxidative protein products, C-reactive protein, interleukin-6, insulin, and cortisol. Astaxanthin supplementation had no statistical effects on markers of substrate metabolism during the GXT, Wingate variables, or markers of muscle damage, inflammation, or DOMS when compared with placebo (all p > 0.05). However, 4 weeks of AX supplementation did significantly lower oxygen consumption during the final stage of the GXT (12%, p = 0.02), as well as lowered systolic blood pressure (~7%, p = 0.04), and significantly lowered baseline insulin values (~24%, p = 0.05) when compared with placebo. Collectively, these data suggest that 4 weeks of AX supplementation at 12 mg·d-1 did not affect markers of muscle damage, inflammation, or DOMS after an EIMD protocol in a resistance-trained male cohort. [ABSTRACT FROM AUTHOR]

The biological activities of Houttuynia cordata (H. cordata) fermented with Aureobasidium pullulans (A. pullulans) was investigated for human skin keratinocyte-induced chemical and photo oxidations. In this research, H2O2/UVA-induced HaCaT cell lines were treated with H. cordata water/ethanol extracts (HCW/HCE) and fermented with A. pullulans water/ethanol extracts (HCFW/HCFE). A. pullulans fermented with H. cordata (HCFW) increased in 5.4-folds of total polyphenol (HCFW 46.89 mg GAE/extract g), and 2.3-folds in flavonoids (HCFW 53.80 mg GAE/extract g) compared with water extracts of H. cordata (HCW). Further, no significant cytotoxicity for HaCaT cells showed by all the extracts of H. cordata fermented with A. pullulans. HCFW extracts have significantly lowered inflammation factors such as COX-2 and Hsp70 proteins in oxidative stressed HaCaT cells induced by H2O2 and UVA treatments. All H. cordata extracts significantly downregulated gene expression involved in oxidative stress and inflammation factors, including IL-1β, IL-6, COX-2, TNF-α, NF-κB, and MMP-1 in the H2O2/UVA-treated HaCaT cells. However, keratin-1 gene expression in the UVA-treated HaCaT cells was increased in twofolds by HCFW extracts. Further, A. pullulans fermented H. cordata extracts (HCFW/HCFE) reduced the genes involved in oxidative stresses more effectively than those of H. cordata extract only. Overall, the polyphenol-rich extracts of H. cordata fermented with A. pullulans showed synergistic protective effects for human epidermal keratinocytes to prevent photoaging and intrinsic aging by anti-oxidation and anti-inflammatory functions. [ABSTRACT FROM AUTHOR]

Purpose: Reactive oxygen and nitrogen species are required for exercise-induced molecular adaptations; however, excessive exercise may cause cellular oxidative distress. We postulate that astaxanthin (ASX) can neutralize oxidative distress and stimulate mitochondrial biogenesis in high-intensity exercise-trained mice. Methods: Six-week-old mice (n = 8/group) were treated with ASX (10 mg/kg BW) or placebo. Training groups participated in 30 min/day high-intensity interval training (HIIT) for 6 weeks. Gastrocnemius muscle was collected and assayed following the exercise training period. Results: Compared to the HIIT control mice, the ASX-treated HIIT mice reduced malonaldehyde levels and upregulated the expression of Nrf2 and FOXO3a. Meanwhile, the genes NQO1 and GCLC, modulated by Nrf2, and SOD2, regulated by FOXO3a, and GPx4, were transcriptionally upregulated in the ASX-treated HIIT group. Meanwhile, the expression of energy sensors, AMPK, SIRT1, and SIRT3, increased in the ASX-treated HIIT group compared to the HIIT control group. Additionally, PGC-1α, regulated by AMPK and SIRT1, was upregulated in the ASX-treated HIIT group. Further, the increased PGC-1α stimulated the transcript of NRF1 and Tfam and mitochondrial proteins IDH2 and ATP50. Finally, the ASX-treated HIIT mice had upregulations in the transcript level of mitochondrial fusion factors, including Mfn1, Mfn2, and OPA1. However, the protein level of AMPK, SIRT1, and FOXO3a, and the transcript level of Nrf2, NQO1, PGC-1α, NRF1, Mfn1, Mfn2, and OPA1 decreased in the HIIT control group compared to the sedentary control group. Conclusion: Supplementation with ASX can reduce oxidative stress and promote antioxidant capacity and mitochondrial biogenesis during strenuous HIIT exercise in mice. [ABSTRACT FROM AUTHOR]

Background. Necrotizing enterocolitis (NEC) is often associated with exaggerated activation of inflammatory response. Astaxanthin has been shown in studies to have a positive and advantageous effect on anti-inflammatory response. Hence, it is of great significance to study the protective effect of astaxanthin in NEC disease and its molecular mechanism. Objective. The present study was to investigate whether astaxanthin attenuates NEC rats and to explore its potential mechanism. Material and Methods. Hematoxylin-eosin staining was used to observe the pathological change of the intestinal tissue in NEC rats. Subsequently, we determined the anti-oxidative stress, anti-apoptosis, and anti-inflammation in astaxanthin with enzyme-linked immunosorbent assay kits, TUNEL staining, western blot, and immunohistochemistry assay. Furthermore, we added nucleotide-binding oligomerization domain 2 (NOD2) inhibitor to certify the molecular pathway of the astaxanthin in NEC rats. Results. Astaxanthin improved the pathological changes of the intestinal tissues. It restrained inflammation, oxidative stress, and protected cells from apoptosis in the intestinal tissue and serum of the NEC rats. Moreover, astaxanthin enhanced NOD2, whereas it suppressed toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) pathway-related proteins. Apart from that, the NOD2 inhibitor offset the protective effect of the astaxanthin towards the NEC rats. Conclusion. The present study indicated that astaxanthin alleviated oxidative stress, inflammatory response, and apoptosis in NEC rats by enhancing NOD2 and inhibiting TLR4 pathway. [ABSTRACT FROM AUTHOR]

Introduction: This is an evaluation of the effects of banana peel BP extract on the heavy metals' mixture HMM mediated oxido-inflammatory effects in the thyroid of female albino rats. Methods: Five groups (5 female rats/group) were treated as follows for 60 days: Group 1: Deionized water only; Group 2: (Pb, Hg, Mn and Al); Group 3: 200 mg/kg BP extract + HMM; Group 4: 400 mg/kg BP extract + HMM; Group 5: 800 mg/kg BP extract + HMM. On day 60 animals were euthanized, thyroid was harvested and used for, malondialdehyde MDA, nitric oxide NO, antioxidants, tumor necrosis factor alpha (TNF – α), interleukin 6 (IL – 6), Caspase-3, Nuclear factor erythroid 2- related factor 2 (Nrf2), Nuclear factor kappa B (NfkB) and Heme Oxygynase – 1 (Hmox-1) and histopathology. Results: There was significant bioaccumulation of Pb, Al, Hg and MN; elevated IL-6 and Tnf-α, MDA and NO, caspase-3 and Nrf2, NF-κB and Hmox-1 in the HMM only group in comparison to the control. There was significant (p < 0.05) decrease in SOD, CAT GSH activities in HMM only exposed group in comparison to the control deionized water group, whereas BP co-treatment with HMM significantly (p < 0.05) increased SOD, CAT GSH activities. Co-treatment with BP extract also reversed most of these effects. Discussion and Conclusions: BP extract may ameliorate HMM -induced thyrotoxicity in female albino rats by blunting oxido-inflammatory activities. [ABSTRACT FROM AUTHOR]

The eye is a metabolically active structure, constantly exposed to solar radiations making its structure vulnerable to the high burden of reactive oxygen species (ROS), presenting many molecular interactions. The biomolecular cascade modification is caused especially in diseases of the ocular surface, cornea, conjunctiva, uvea, and lens. In fact, the injury in the anterior segment of the eye takes its origin from the perturbation of the pro-oxidant/antioxidant balance and leads to increased oxidative damage, especially when the first line of antioxidant defence weakens with age. Furthermore, oxidative stress is related to mitochondrial dysfunction, DNA damage, lipid peroxidation, protein modification, apoptosis, and inflammation, which are involved in anterior ocular disease progression such as dry eye, keratoconus, uveitis, and cataract. The different pathologies are interconnected through various mechanisms such as inflammation, oxidative stress making the diagnostics more relevant in early stages. The end point of the molecular pathway is the release of different antioxidant biomarkers offering the potential of predictive diagnostics of the pathology. In this review, we have analysed the oxidative stress and inflammatory processes in the front of the eye to provide a better understanding of the pathomechanism, the importance of biomarkers for the diagnosis of eye diseases, and the recent treatment of anterior ocular diseases. [ABSTRACT FROM AUTHOR]

A moderate amount of reactive oxygen species (ROS) is produced under normal conditions, where they play an important role in cell signaling and are involved in many aspects of the immune response to pathogens. On the other hand, the excessive production of ROS destructs macromolecules, cell membranes, and DNA, and activates pro-inflammatory signaling pathways, which may lead to various pathologic conditions. Gastrointestinal (GI) mucosa is constantly exposed to ROS due to the presence of bacteria and other infectious pathogens in food, as well as alcohol consumption, smoking, and the use of non-steroidal anti-inflammatory drugs (NSAID). Prolonged excessive oxidative stress and inflammation are two major risk factors for GI disorders such as ulcers and cancers. Bioactive food compounds with potent anti-oxidant and anti-inflammatory activity have been tested in experimental GI disease models to evaluate their therapeutic potential. Astaxanthin (AST) is a fat-soluble xanthophyll carotenoid that is naturally present in algae, yeast, salmon, shrimp, and krill. It has been shown that AST exhibits protective effects against GI diseases via multiple mechanisms. Residing at the surface and inside of cell membranes, AST directly neutralizes ROS and lipid peroxyl radicals, enhances the activity of anti-oxidant enzymes, and suppresses pro-inflammatory transcription factors and cytokines. In addition, AST has been shown to inhibit cancer cell growth and metastasis via modulating cell proliferation-related pathways, apoptosis, and autophagy. Considering the potential benefits of AST in GI diseases, this review paper aims to summarize recent advances in AST research, focusing on its anti-oxidant and anti-inflammatory effects against gastric and intestinal ulcers and cancers. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to investigate the effect of olive cake (OC) on oxidant/antioxidant biomarkers, lipase activity and on the histological analysis of epididymal fat, in high-fat diet (HFD)-induced obese rats. Design/methodology/approach: Male obese rats were divided into two groups and were fed an HFD supplemented (HFD-OC) or not (HFD) with OC for 28 days. A control group was fed a standard diet for the same experimental period. Findings: HFD significantly increased body weight, which was reduced by OC in the HFD-OC compared to HFD (p = 0.038). Lipase activity was higher (52%; p = 0.009) in the HFD group than the control group. Administration of OC to the obese rats decreased significantly this activity (38%; p = 0.025) compared to the HFD group. Serum thiobarbituric acid-reactive substances, lipid hydroperoxide and advanced oxidation protein products levels were significantly increased in the HFD group than the control group (p = 0.032, p = 0.023 and p = 0.017, respectively). These levels were significantly reduced in HFD-OC compared to the HFD group (p = 0.030, p = 0.021 and p = 0.010, respectively). Superoxide dismutase, glutathione peroxidase and catalase activities were decreased (53%; p = 0.04), (61%; p = 0.03) and (32%; p = 0.002), in the HFD group than the control group. OC restored these activities (46%; p = 0.01), (58%; p = 0.003) and (30%; p = 0.0003) in the HFD-OC rats than the HFD rats. Consumption of the HFD resulted in adipocyte hypertrophy. Indeed, epididymal adipocyte size was significantly larger in the HFD group than the control group (p = 0.0001), whereas it was reduced in the HFD-OC compared to the HFD group (p = 0.012). Originality/value: OC possesses an anti-obesity effect. This effect might be mediated by lipase inhibition, reduced oxidative stress and increased antioxidant activities. In addition, the reduction of fat accumulation in adipose tissue by OC consumption is reflected by reducing adipocyte size. [ABSTRACT FROM AUTHOR]

Neuroinflammation plays a significant role in the aging process and the pathophysiology of neurodegenerative diseases, such as Alzheimer's disease. Accordingly, possible therapeutic strategies aimed at anti-inflammatory effects may be beneficial to brain health. Walnut kernels contain large quantities of unsaturated fatty acids, peptides, and phenolic compounds that have anti-inflammatory effects. The long-term intake of walnuts has been found to improve cognitive function and memory in rats and humans. However, the modulatory effect of walnuts on neuroinflammation has received much less attention. This review focuses on the potential influence and main regulating mechanisms of walnuts and their active ingredients on neuroinflammation, including the regulation of microglia activation induced by amyloid β or lipopolysaccharides, inhibition of peripheral inflammation mediated by macrophages, reduction in oxidative stress by decreasing free radical levels and boosting antioxidant defenses, and control of gut microbes to maintain homeostasis. However, the majority of evidence of the beneficial effects of walnuts or their components on neuroinflammation and neurodegeneration comes from experimental work, whereas evidence from clinical studies on the beneficial effects is scarcer and less conclusive. This review aims to provide new insights into the neuroinflammation-regulating mechanisms and natural active ingredients of walnuts and the development of walnut-based functional foods for the alleviation of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Diabetes remains a major health emergency in our entire world, affecting hundreds of millions of people worldwide. In conjunction with its much-dreaded complications (e.g., nephropathy, neuropathy, retinopathy, cardiovascular diseases, etc.) it substantially reduces the quality of life, increases mortality as well as economic burden among patients. Over the years, oxidative stress and inflammation have been highlighted as key players in the development and progression of diabetes and its associated complications. Much research has been devoted, as such, to the role of antioxidants in diabetes. Astaxanthin is a powerful antioxidant found mostly in marine organisms. Over the past years, several studies have demonstrated that astaxanthin could be useful in the treatment and management of diabetes. It has been shown to protect β-cells, neurons as well as several organs including the eyes, kidney, liver, etc. against oxidative injuries experienced during diabetes. Furthermore, it improves glucose and lipid metabolism along with cardiovascular health. Its beneficial effects are exerted through multiple actions on cellular functions. Considering these and the fact that foods and natural products with biological and pharmacological activities are of much interest in the 21st-century food and drug industry, astaxanthin has a bright prospect in the management of diabetes and its complications. [ABSTRACT FROM AUTHOR]

OBJECTIVE Radiation (RT)-induced intestinal toxicity is a common complication of abdominal or pelvic radiation therapy. Although the underlying pathological features are partially clarified, the appropriate treatment approach is not yet clear. Herein, we sought the protective role of astaxanthin (ATX), which is a natural antioxidant, on the RT-induced toxicity in the rat intestine. METHODS Male Wistar rats that are 10-12 weeks old and weighing 250-350 g were divided into four groups: control, RT alone, RT+ATX, and ATX alone as Groups 1, 2, 3, and 4, respectively. RT was given to the abdomen as one fraction of 8 Gy, and ATX was given as 4 mg/kg for 7 days before RT. Intestinal tissues were taken 24 h after the last ATX injection and radiation for histopathologic, immunohistochemical examination, and oxidative stress measurement. RESULTS Oxidative stress index and oxidant status decreased with ATX administration in the radiation group where an increase was reported in total antioxidant status. ATX treatment decreased the pathological expressions observed in the proprial and epithelial cells of the intestinal villi in the RT group. Similarly, RT exposure increased TNF-α expression while ATX treatment decreased the immunoreaction. CONCLUSION Our results demonstrate that radiation induces apoptosis and histopathologic intestinal mucosal changes which leads to an increase in oxidative stress. ATX significantly ameliorates radiation-induced reactions with its superior antioxidant properties and additional anti-inflammatory and antiapoptotic activities. [ABSTRACT FROM AUTHOR]

Obesity is a main risk factor for the onset and the precipitation of many non-communicable diseases. This condition, which is associated with low-grade chronic systemic inflammation, is of main concern during pregnancy leading to very serious consequences for the new generations. In addition to the prominent role played by the adipose tissue, dysbiosis of the maternal gut may also sustain the obesity-related inflammatory milieu contributing to create an overall suboptimal intrauterine environment. Such a condition here generically defined as "inflamed womb" may hold long-term detrimental effects on fetal brain development, increasing the vulnerability to mental disorders. In this review, we will examine the hypothesis that maternal obesity-related gut dysbiosis and the associated inflammation might specifically target fetal brain microglia, the resident brain immune macrophages, altering neurodevelopmental trajectories in a sex-dependent fashion. We will also review some of the most promising nutritional strategies capable to prevent or counteract the effects of maternal obesity through the modulation of inflammation and oxidative stress or by targeting the maternal microbiota. [ABSTRACT FROM AUTHOR]

The gastrointestinal tract is a unique organ containing both vascular and luminal routes lined by epithelial cells forming the mucosa, which play an important role in the entry of nutrients and act as a selective barrier, excluding potentially harmful agents. Mucosal surfaces establish a selective barrier between hostile external environments and the internal milieu. Heme is a major nutritional source of iron and is a pro-oxidant that causes oxidative stress. Heme oxygenases (HOs) catalyze the rate-limiting step in heme degradation, resulting in the formation of iron, carbon monoxide, and biliverdin, which are subsequently converted to bilirubin by biliverdin reductase. In gastrointestinal pathogenesis, HO-1, an inducible isoform of HO, is markedly induced in epithelial cells and plays an important role in protecting mucosal cells. Recent studies have focused on the biological effects of the products of this enzymatic reaction, which have antioxidant, anti-inflammatory, and cytoprotective functions. In this review, the essential roles of HO in the gastrointestinal tract are summarized, focusing on nutrient absorption, protection against cellular stresses, and the maintenance and regulation of tight junction proteins, emphasizing the potential therapeutic implications. The biochemical basis of the potential therapeutic implications of glutamine for HO-1 induction in gastrointestinal injury is also discussed. [ABSTRACT FROM AUTHOR]

Green tea extract (GTE) improves exercise outcomes and reduces obesity. However, case studies indicate contradictory physiology regarding liver function and toxicity. We studied the effect of two different decaffeinated GTE (dGTE) products, from a non-commercial (dGTE1) and commercial (dGTE2) supplier, on hepatocyte function using the human cell model, HepG2. dGTE1 was protective against hydrogen peroxide (H2O2)-induced apoptosis and cell death by attenuating oxidative stress pathways. Conversely, dGTE2 increased cellular and mitochondrial oxidative stress and apoptosis. A bioavailability study with dGTE showed the major catechin in GTE, EGCG, reached 0.263 µg·ml−1. In vitro, at this concentration, EGCG mimicked the protective effect of dGTE1. GC/MS analysis identified steric acid and higher levels of palmitic acid in dGTE2 versus dGTE1 supplements. We demonstrate the significant biological differences between two GTE supplements which may have potential implications for manufacturers and consumers to be aware of the biological effects of supplementation. [ABSTRACT FROM AUTHOR]

Astaxanthin (AST) has a variety of biochemical effects, including anti-inflammatory, antioxidative, and antihypertensive functions. The aim of the present study was to determine whether AST ameliorates blood pressure in salt-induced prehypertensive rats by ROS/MAPK/NF-κB pathways in hypothalamic paraventricular nucleus. To explore the central effects of AST on the development of blood pressure, prehypertensive rats were induced by a high-salt diet (HS, 8% NaCl) and its control groups were treated with normal-salt diet (NS, 0.3% NaCl). The Dahl salt-sensitive (S) rats with HS diet for 6 weeks received AST or vehicle by gastric perfusion for 6 weeks. Compared to those with NS diet, rats with HS diet exhibited increased mean arterial pressure (MAP) and heart rate (HR). These increases were associated with higher plasma level of norepinephrine (NE), interleukin 1β (IL-1β), and interleukin 6 (IL-6); elevated PVN level of reactive oxygen species (ROS), NOX2, and NOX4, that of IL-1β, IL-6, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), phosphorylation extracellular-signal-regulated kinase (p-ERK1/2), phosphorylation Jun N-terminal kinases (p-JNK), nuclear factor-kappa B (NF-κB) activity; and lower levels of IL-10, superoxide dismutase (SOD), and catalase (CAT) in the PVN. In addition, our data demonstrated that chronic AST treatment ameliorated these changes in the HS but not NS diet rats. These data suggested that AST could alleviate prehypertensive response in HS-induced prehypertension through ROS/MAPK/NF-κB pathways in the PVN. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress and inflammation play pivotal roles in the pathophysiology of obesity and depression. This study aimed to evaluate the effects of sumac (Rhus coriaria L.) on anthropometric indices, oxidative stress, inflammation, and depression in overweight or obese depressed women. Methods: This randomized, double‐blind, placebo‐controlled clinical trial was conducted on overweight or obese women aged 20–65 years with mild to moderate depression. The participants (n = 62) were assigned to receive a restricted calorie diet (RCD) plus 3 g/day of either sumac or placebo for 12 weeks. Anthropometric measurements, biochemical biomarkers, and the Beck depression inventory were assessed during the study. Results: Sumac significantly reduced weight, body mass index, body fat (p <.001), visceral fat level (p =.03), waist and hip circumference, and malondialdehyde levels (p =.03, p =.002, and p =.006, respectively) in comparison with the placebo group. The levels of interleukin‐6 and tumor necrosis factor‐α decreased only in the sumac group (11 and 32%, respectively); however, these reductions were not significant. The high‐sensitivity c‐reactive protein levels (p =.007 and p =.01, respectively) and Beck scores (p <.001) decreased significantly in both the sumac and the placebo group without any significant difference between the two groups. Conclusion: Sumac can be considered as a functional food that along with RCD could have beneficial effects on obesity management, through the possible modulatory effects on oxidative stress in overweight or obese depressed women. [ABSTRACT FROM AUTHOR]

Alterations in molecular signaling impair cellular functions and induce degenerative diseases. Among the factors affecting intracellular signaling pathways, oxidative stress serves an important role. Astaxanthin (3,3-dihydroxy-β, β-carotene-4,4-dione), a pigment found in aquatic organisms, belongs to the xanthophylls family. Astaxanthin exerts a strong antioxidant activity and is widely used in food, cosmetic and pharmaceutical industries. Oxidative stress damages bone homeostasis by producing reactive oxygen species and increasing the production of pro-resorption cytokines, such as interleukin (IL)-1, tumor necrosis factor-α and IL-6. Therefore, antioxidant molecules can counteract the negative effects of oxidative stress on bone. Accordingly, previous studies have demonstrated that supplementation of astaxanthin in bone contributes to the restoration of bone homeostasis. The present review summarizes the negative effects of oxidative stress in bone and explores the role of astaxanthin in counteracting skeletal injuries consequent to oxidative stress. [ABSTRACT FROM AUTHOR]

The skin is the first line of defense against pathogen and other environmental pollutant. The body is constantly exposed to reactive oxygen species (ROS) that stimulates inflammatory process in the skin. Many studies have linked ROS to various inflammatory skin diseases. Patients with skin diseases face various challenges with inefficient and inappropriate treatment in managing skin diseases. Overproduction of ROS in the body will result in oxidative stress which will lead to various cellular damage and alter normal cell function. Multiple signaling pathways are seen to have significant effects during ROS-mediated oxidative stress. In this review, microalgae have been selected as a source of natural-derived antioxidant to combat inflammatory skin diseases that are prominent in today's society. Several studies have demonstrated that bioactive compounds isolated from microalgae have anti-inflammation and anti-oxidative properties that can help remedy various skin diseases. These compounds are able to inhibit production of pro-inflammatory cytokines and reduce the expression of inflammatory genes. Bioactive compounds from microalgae work in action by altering enzyme activities, regulating cellular activities, targeting major signaling pathways related to inflammation. [ABSTRACT FROM AUTHOR]

Background: The physical fatigue can disturb the quality of work outcome and quality of life. However, the pharmacological therapy against this condition has not yet satisfied the requirement of people. Therefore, the anti-fatigue regimen which is cheap, safe, less toxic and easy to approach is required. Based on the role of oxidative stress on the contractile dysfunction of muscle, the antifatigue effect of sugarcane pomace which possesses antioxidant effect has gained attention. However, no evidence concerning this issue is available. Objective: To determine the anti-fatigue effect and the possible mechanism of the extract of sugarcane bagasse. Materials and Methods: Male Wistar rats were randomly divided into 5 groups: control, vehicle, sugarcane bagasse extract 50, 150, 450 mg.kg-1BW. Rats in all groups except those in control group were treated with the assigned substance once daily via oral route for 28 days. Exhaustive swimming time was assessed every 7 days. At the end of study, gastrocnemius, soleus and extensor digitorum longus (EDL) were isolated and determined oxidative stress markers and the muscle fiber density and diameter. Results: All doses of extract used in this study showed anti-fatigue effect. The possible mechanism might depend on the dose of extract. Low and medium doses exerted the effect via the alteration of muscle morphology in gastrocnemius and soleus respectively whereas high dose of extract showed the effect mainly via the decreased oxidative stress in soleus muscle. Conclusion: Sugarcane bagasse extract has the potential to be developed as an anti-fatigue active ingredient in health products. However, further studies are required to elucidate the precise underlying mechanism and the possible active ingredients. [ABSTRACT FROM AUTHOR]

Cyclosporin A (CsA) is a common immunosuppressant, but its use is limited as it can cause chronic kidney injury. Oxidative stress and apoptosis play a key role in CsA‐induced nephrotoxicity. This study investigated the protective effect of 5‐aminolevulinic acid and iron (5‐ALA/SFC) on CsA‐induced injury in murine proximal tubular epithelial cells (mProx24). 5‐ALA/SFC significantly inhibited apoptosis in CsA‐treated mProx24 cells with increases in heme oxygenase (HO)‐1, nuclear factor E2‐related factor 2 (Nrf2), and p38, and Erk‐1/2 phosphorylation. Moreover, 5‐ALA/SFC suppressed production of reactive oxygen species in CsA‐exposed cells and inhibition of HO‐1 suppressed the protective effects of 5‐ALA/SFC. In summary, 5‐ALA/SFC may have potential for development into a treatment for the anti‐nephrotoxic/apoptotic effects of CsA. [ABSTRACT FROM AUTHOR]

Background: Arachidonic acid (AA, C20:4, ω-6) is a ω-6 polyunsaturated fatty acid (PUFA) and plays diverse roles in cell signaling. Numerous reports on the effects of ω-3 PUFAs, such as docosahexaenoic acid (DHA, C22:6, ω-3) and eicosapentaenoic acid (EPA, C20:5, ω-3) on learning and memory impairments of rats are available, however, the role of AA on brain cognition is largely unknown. Objective: In this study, our aim was to investigate the effect of oral administration of AA on spatial memory- related learning ability in aged (100 weeks) male rats. Design: One group was per orally administered 240 mg/kg per day AA oil and the other group was administered the similar volume of control oil. Five weeks after the start of the administration, rats were tested with the partially baited eight-arm radial maze to evaluate two types of spatial memory-related learning ability displayed by reference memory errors (RMEs) and working memory errors (WMEs). Also, the time required to complete the task was recorded. The levels of lipid peroxide (LPO) and reactive oxygen species (ROS) were measured, as an indicator oxidative stress in the plasma and brain corticohippocampal brain tissues. Results: The scores of RMEs and WMEs, which are analogous to long-term and short-term memory, respectively, were not affected, however, the trial time was shorter in the AA-administered rats than that of the controls. AA also significantly increased the degree of oxidative stress both in the plasma and corticohippocampal brain tissues. Conclusions: Our results suggest that though AA deposition in the corticohippocampal tissues of senescent rats caused a faster performance activity, which is reminiscent to hyperactive behavior of animals, the spatial learning ability-related memory of the rats, however, was not improved. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI), which is defined as a rapid decline of renal function, becomes common and recently recognized to be closely intertwined with chronic kidney diseases. Current treatment for AKI is largely supportive, and endoplasmic reticulum (ER) stress has emerged as a novel mediator of AKI. Since carbon monoxide attenuates ER stress, the objective of the present study aimed to determine the protective effect of carbon monoxide releasing molecule-2 (CORM2) on AKI associated with ER stress. Kidney injury was induced after LPS (15 mg/kg) treatment at 12 to 24 h in C57BL/6J mice. Pretreatment of CORM2 (30 mg/kg) effectively prevented LPS-induced oxidative stress and inflammation during AKI in mice. CORM2 treatment also effectively inhibited LPS-induced ER stress in AKI mice. In order to confirm effect of CO on the pathophysiological role of tubular epithelial cells in AKI, we used mProx24 cells. Pretreatment of CORM2 attenuated LPS-induced ER stress, oxidative stress, and inflammation in mProx24 cells. These data suggest that CO therapy may prevent ER stress-mediated AKI. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effect of astaxanthin on isoproterenol (ISO)-induced myocardial infarction and cardiac hypertrophy in rats. To evaluate the effect of astaxanthin on ISOinduced cardiac dysfunction, 18 aged Long Evans male rats were evenly divided into three groups. Group I (Control group) was given only the laboratory-ground food and normal water. Group II (ISO group) was administered ISO at a dose of 50 mg/kg subcutaneously (SC) twice a week for two weeks. Group III (Astaxanthin + ISO group) was treated with astaxanthin (25 mg/kg) orally every day and ISO 50 mg/kg SC twice a week for two weeks. ISO administration in rats increased the heart and left ventricular wet weights and increased inflammatory cell infiltration and fibrosis. Moreover, ISO administration increased the lipid peroxidation and decreased antioxidant enzyme activities in heart tissues. Astaxanthin treatment prevented the increased wet weight of heart and decreased inflammatory cell infiltration and fibrosis. The protective effect of astaxanthin was associated with reduction of free radicals by improving antioxidant enzyme function, as well as normalization and/or suppression of elevated oxidative stress markers, such as malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) in ISO-administered rats. Furthermore, astaxanthin decreased the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), and creatinin kinase muscle/brain (CK-MB) in ISO-administered rats. In conclusion, astaxanthin may protect cardiac tissues in ISO-administered rats through suppression of oxidative stress and enhancement of antioxidant enzyme functions. [ABSTRACT FROM AUTHOR]

For many years, oxidative stress arising from the ubiquitous production of reactive oxygen species (ROS) has been implicated in the pathogenesis of various eye diseases. While emerging research has provided some evidence of the important physiological role of ROS in normal cell function, disease may arise where the concentration of ROS exceeds and overwhelms the body's natural defence against them. Additionally, ROS may induce genomic aberrations which affect cellular homoeostasis and may result in disease. This literature review examines the current evidence for the role of oxidative stress in important ocular diseases with a view to identifying potential therapeutic targets for future study. The need is particularly pressing in developing treatments for conditions which remain notoriously difficult to treat, including glaucoma, diabetic retinopathy and age-related macular degeneration. [ABSTRACT FROM AUTHOR]

Acute or chronic oxidative stress plays an important role in many pathologies. Two opposite approaches are typically used to prevent the damage induced by reactive oxygen and nitrogen species (RONS), namely treatment either with antioxidants or with weak oxidants that up-regulate endogenous antioxidant mechanisms. This review discusses options for the third pharmacological approach, namely amelioration of oxidative stress by 'redox-inert' compounds, which do not inactivate RONS but either inhibit the basic mechanisms leading to their formation (i.e. inflammation) or help cells to cope with their toxic action. The present study describes biochemical targets of many drugs mitigating acute oxidative stress in animal models of ischemia-reperfusion injury or N-acetylp-aminophenol overdose. In addition to the pro-inflammatory molecules, the targets of mitigating drugs include protein kinases and transcription factors involved in regulation of energy metabolism and cell life/death balance, proteins regulating mitochondrial permeability transition, proteins involved in the endoplasmic reticulum stress and unfolded protein response, nuclear receptors such as peroxisome proliferator-activated receptors, and isoprenoid synthesis. The data may help in identification of oxidative stress mitigators that will be effective in human disease on top of the current standard of care. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is histopathologically characterized by the build-up of fibrillar amyloid beta (Aβ) in the form of amyloid plaques and the development of intraneuronal neurofibrillary tangles consisting of aggregated hyperphosphorylated Tau. Although amyloid fibrils were originally considered responsible for AD pathogenesis, recent convincing evidence strongly implicates soluble oligomeric Aβ as the primary neurotoxic species driving disease progression. A third largely ignored pathological hallmark, originally described by Alois Alzheimer, is the presence of "adipose inclusions", suggestive of aberrant lipid metabolism. The molecular mechanisms underlying these "lipoid granules", as well as their potential link to soluble and/or fibrillar Aβ remain largely unknown. Seeking to better-understand these conundrums, we took advantage of the powerful technology of multidimensional mass spectrometry-based shotgun lipidomics and an AD transgenic mouse model overexpressing mutant amyloid precursor protein (APP E693Δ-Osaka-), where AD-like pathology and neurodegeneration occur as a consequence of oligomeric Aβ accumulation in the absence of amyloid plaques. Our results revealed for the first time that APP overexpression and oligomeric Aβ accumulation lead to an additive global accumulation of nonesterified polyunsaturated fatty acids (PUFAs) independently of amyloid plaques. Furthermore, we revealed that this accumulation is mediated by an increase in phospholipase A2 (PLA2) activity, evidenced by an accumulation of sn-1 lysophosphatidylcholine and by MAPK-mediated phosphorylation/activation of group IV CA2+-dependent cytosolic (cPLA2) and the group VI Ca2+-independent PLA2 (iPLA2) independently of PKC. We further revealed that Aβ-induced oxidative stress also disrupts lipid metabolism via reactive oxygen species-mediated phospholipid cleavage leading to increased sn-2 lysophosphatidylcholine as well as lipid peroxidation and the subsequent accumulation of 4-hydroxynonenal. Brain histological studies implicated cPLA2 activity with arachidonic acid accumulation within myelin-rich regions, and iPLA2 activity with docosahexaenoic acid accumulation within pyramidal neuron-rich regions. Taken together, our results suggest that PLA2-mediated accumulation of free PUFAs drives AD-related disruption of brain lipid metabolism. [ABSTRACT FROM AUTHOR]

Oxidative stress is a well-described imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense system of cells and tissues. The overproduction of free radicals damages all components of the cell (proteins, lipids, nucleic acids) and modifies their physiological functions. As widely described, this condition is a biochemical hallmark of chronic kidney disease (CKD) and may dramatically influence the progression of renal impairment and the onset/development of major systemic comorbidities including cardiovascular diseases. This state is exacerbated by exposure of the body to uremic toxins and dialysis, a treatment that, although necessary to ensure patients' survival, exposes cells to non-physiological contact with extracorporeal circuits and membranes with consequent mitochondrial and anti-redox cellular system alterations. Therefore, it is undeniable that counteracting oxidative stress machinery is a major pharmacological target in medicine/nephrology. As a consequence, in recent years several new naturally occurring compounds, administered alone or integrated with classical therapies and an appropriate lifestyle, have been proposed as therapeutic tools for CKD patients. In this paper, we reviewed the recent literature regarding the "pioneering" in vivo testing of these agents and their inclusion in small clinical trials performed in patients affected by CKD. [ABSTRACT FROM AUTHOR]

Catechins are natural polyphenolic phytochemicals that exist in food and medicinal plants, such as tea, legume and rubiaceae. An increasing number of studies have associated the intake of catechins-rich foods with the prevention and treatment of chronic diseases in humans, such as inflammatory bowel disease (IBD). Some studies have demonstrated that catechins could significantly inhibit the excessive oxidative stress through direct or indirect antioxidant effects and promote the activation of the antioxidative substances such as glutathione peroxidases (GPO) and glutathione (GSH), reducing the oxidative damages to the colon. In addition, catechins can also regulate the infiltration and proliferation of immune related-cells, such as neutrophils, colonic epithelial cells, macrophages, and T lymphocytes, helping reduce the inflammatory relations and provide benefits to IBD. Perhaps catechins can further inhibit the deterioration of intestinal lesions through regulating the cell gap junctions. Furthermore, catechins can exert their significant anti-inflammatory properties by regulating the activation or deactivation of inflammation-related oxidative stress-related cell signaling pathways, such as nuclear factor-kappa B (NF-κB), mitogen activated protein kinases (MAPKs), transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), signal transducer and the activator of transcription 1/3 (STAT1/3) pathways. Finally, catechins can also stabilize the structure of the gastrointestinal micro-ecological environment via promoting the proliferation of beneficial intestinal bacteria and regulating the balance of intestinal flora, so as to relieve the IBD. Furthermore, catechins may regulate the tight junctions (TJ) in the epithelium. This paper elaborates the currently known possible molecular mechanisms of catechins in favor of IBD. [ABSTRACT FROM AUTHOR]

Background: The hematopoietic system is especially sensitive to total body irradiation (TBI), and myelosuppression is one of the major effects of TBI. Astaxanthin (ATX) is a powerful natural anti-oxidant with low toxicity. In this study, the effect of ATX on hematopoietic system injury after TBI was investigated. Methods: Flow cytometry was used to detect the proportion of hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs), the level of intracellular reactive oxygen species (ROS), expression of cytochrome C, cell apoptosis, and NRF2-related proteins. Immunofluorescence staining was used to detect Nrf2 translocation. Western blot analysis was used to evaluate the expression of apoptotic-related proteins. Enzymatic activities assay kits were used to analyze SOD2, CAT, and GPX1 activities. Results: Compared with the TBI group, ATX can improve radiation-induced skewed differentiation of peripheral blood cells and accelerate hematopoietic self-renewal and regeneration. The radio-protective effect of ATX is probably attributable to the scavenging of ROS and the reduction of cell apoptosis. These changes were associated with increased activation of Nrf2 and downstream anti-oxidative proteins, and regulation of apoptotic-related proteins. Conclusions: This study suggests that ATX could be used as a potent therapeutic agent to protect the hematopoietic system against TBI-induced bone marrow suppression. [ABSTRACT FROM AUTHOR]

Hydrogen gas reduces ischemia and reperfusion injury (IRI) in the liver and other organs. However, the precise mechanism remains elusive. We investigated whether hydrogen gas ameliorated hepatic I/R injury after cold preservation. Rat liver was subjected to 48-h cold storage in University of Wisconsin solution. The graft was reperfused with oxygenated buffer with or without hydrogen at 37° for 90 min on an isolated perfusion apparatus, comprising the H2(+) and H2(−) groups, respectively. In the control group (CT), grafts were reperfused immediately without preservation. Graft function, injury, and circulatory status were assessed throughout the perfusion. Tissue samples at the end of perfusion were collected to determine histopathology, oxidative stress, and apoptosis. In the H2(−) group, IRI was indicated by a higher aspartate aminotransferase (AST), alanine aminotransferase (ALT) leakage, portal resistance, 8-hydroxy-2-deoxyguanosine-positive cell rate, apoptotic index, and endothelial endothelin-1 expression, together with reduced bile production, oxygen consumption, and GSH/GSSG ratio (vs. CT). In the H2(+) group, these harmful changes were significantly suppressed [vs. H2(−)]. Hydrogen gas reduced hepatic reperfusion injury after prolonged cold preservation via the maintenance of portal flow, by protecting mitochondrial function during the early phase of reperfusion, and via the suppression of oxidative stress and inflammatory cascades thereafter. [ABSTRACT FROM AUTHOR]

Objective:The present study investigated the role of N-methyl-d-aspartate (NMDA) receptors in curcumin-mediated renoprotection against ischemia reperfusion (I/R)-induced acute kidney injury (AKI) in rats. Methods:Rats were subjected to bilateral renal I/R (40 min I, 24 hours R) to induce AKI. Kidney injury was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, potassium level, fractional excretion of sodium, and macroproteinuria. Oxidative stress in renal tissues was assessed by measuring myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione content. Hematoxylin & eosin staining was done to assess histological changes in renal tissues. Curcumin (30 and 60 mg/kg) was administered one hour before subjecting rats to AKI. In separate groups, NMDA receptor agonists, glutamic acid (200 mg/kg), and spermidine (20 mg/kg) were administered prior to curcumin treatment in rats followed by AKI. Results:I/R-induced AKI was demonstrated by significant change in plasma and urine parameters along with marked increase in oxidative stress and histological changes in renal tissues that were aggravated with pretreatment of glutamic acid and spermidine in rats. Administration of curcumin resulted in significant protection against AKI. However, glutamic acid and spermidine pretreatments prevented curcumin-mediated renoprotection. Conclusion:It is concluded that NMDA receptor antagonism significantly contributes towards curcumin-mediated protection against I/R-induced AKI. [ABSTRACT FROM AUTHOR]

Both oxidative stress and inflammation are involved in the pathogenesis of contrast-induced nephropathy (CIN). Epigallocatechin-3-gallate (EGCG), a purified catechin from green tea, has antioxidant and anti-inflammatory effects. However, it is unknown whether or not EGCG is effective in treating CIN. Our present study found that intravenous administration of EGCG, either before or just after the establishment of CIN, had a protective effect, determined by normalization of serum creatinine and blood urea nitrogen levels, improvement in renal histopathological scoring and alleviation of apoptosis, accompanied by decreased oxidative stress and inflammation. Because EGCG is a potent inducer of the antioxidant heme oxygenase-1 (HO-1), we studied HO-1 signaling in CIN. HO-1 levels were increased in CIN; treatment with EGCG further increased HO-1 levels, accompanied by an increase in Nrf2, a regulator of antioxidant proteins. Interestingly, blockade of HO-1 with protoporphyrin IX zinc(II) (ZnPP) prevented the protective effect of EGCG on CIN. ZnPP also blocked the ability of EGCG to increase the activity of an antioxidant (superoxide dismutase), and decrease markers of oxidative stress (myeloperoxidase and malondialdehyde) and inflammation (myeloperoxidase and IL-1β), indicating that HO-1 is the upstream molecule that regulates the EGCG-mediated protection. To determine further the role of HO-1 on the EGCG-mediated inhibition of inflammation, we studied the effect of EGCG on the NLRP3 inflammasome, an upstream signaling of IL-1β. EGCG down-regulated NLRP3 expression, which was blocked by ZnPP, indicating that HO-1 links EGCG with NLRP3. Therefore, EGCG, via up-regulation of HO-1, protects against CIN by amelioration of oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated whether orally administered astaxanthin (AST) protects against oxidative damage in the ocular tissues of streptozotocin (STZ)-induced diabetic rats. Methods and Results: Fifty 6-week-old female Wistar rats were randomly assigned to receive an injection of STZ to induce diabetes (n = 40) or to remain uninduced (n = 10). The diabetic rats were randomly selected into four groups and they were separately administered normal saline, 0.6 mg/kg AST, 3 mg/kg AST, or 0.5 mg/kg lutein daily for eight weeks. Retinal functions of each group were evaluated by electroretinography. The expression of oxidative stress and inflammatory mediators in the ocular tissues was then assessed by immunohistochemistry, western blot analysis, ELISA, RT-PCR, and electrophoretic mobility shift assay (EMSA). Retinal functions were preserved by AST and lutein in different levels. Ocular tissues from AST- and lutein-treated rats had significantly reduced levels of oxidative stress mediators (8-hydroxy-2'-deoxyguanosine, nitrotyrosine, and acrolein) and inflammatory mediators (intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and fractalkine), increased levels of antioxidant enzymes (heme oxygenase-1 and peroxiredoxin), and reduced activity of the transcription factor nuclear factor-kappaB (NF-κB). Conclusion: The xanthophyll carotenoids AST and lutein have neuroprotective effects and reduce ocular oxidative stress, and inflammation in the STZ diabetic rat model, which may be mediated by downregulation of NF-κB activity. [ABSTRACT FROM AUTHOR]

Neurological diseases, which consist of acute injuries and chronic neurodegeneration, are the leading causes of human death and disability. However, the pathophysiology of these diseases have not been fully elucidated, and effective treatments are still lacking. Astaxanthin, a member of the xanthophyll group, is a red-orange carotenoid with unique cell membrane actions and diverse biological activities. More importantly, there is evidence demonstrating that astaxanthin confers neuroprotective effects in experimental models of acute injuries, chronic neurodegenerative disorders, and neurological diseases. The beneficial effects of astaxanthin are linked to its oxidative, anti-inflammatory, and anti-apoptotic characteristics. In this review, we will focus on the neuroprotective properties of astaxanthin and explore the underlying mechanisms in the setting of neurological diseases. [ABSTRACT FROM AUTHOR]

Purpose: To examine whether astaxanthin (AST) prevent the cataract formation induced by glucocorticoid in chick embryo. Materials and methods: Hydrocortisone hemisuccinate sodium (HC) (0.5 μmol/egg) was administered directly into the air chamber in the egg shell of chick embryo day 15. The eggs were then kept in an incubator at same conditions and administered 100 μL of 50 (HC + AST50 group), 80 (HC + AST80 group), 100 (HC + AST100 group) mg/mL of AST solutions dissolved in dimethyl sulfoxide (DMSO) 3 h after administration of HC. In addition, non-HC treated group (treated with physiological saline without HC and 100 μL of DMSO), HC-alone group (treated with 0.5 μmol of HC and 100 μL of DMSO), and AST100 group (treated with physiological saline without HC and 100 μL of DMSO) were also incorporated. After 48 h of treatment, lenses were removed from embryo and classified into five stages according to developed opacity. The amounts of reduced glutathione in the lenses and the blood glucose levels were measured. Results: The average scores of lens opacitiy were 2.63 ± 1.02 nmol/lens (HC-alone), 2.78 ± 0.97 nmol/lens (HC + AST50), 2.22 ± 1.20 nmol/lens (HC + AST80) and 1.84 ± 0.83 nmol/lens (HC + AST100; p < 0.05), respectively. Administration of AST decreased the lens opacity dose-dependently. The amounts of reduced glutathione in lenses were 11.6 ± 2.8 nmol/lens (HC-alone), 11.3 ± 2.7 nmol/lens (HC + AST50), 13.4 ± 2.4 nmol/lens (HC + AST80) and 13.7 ± 3.1 nmol/lens (HC + AST100; p < 0.05), respectively. Higher levels of AST prevented loss of reduced glutathione from the lens. Conclusion: These findings support that AST protects glucocorticoid-induced cataract in chick embryo. [ABSTRACT FROM AUTHOR]

Introduction: Many studies have shown that oral supplementation with astaxanthin may be a novel potential treatment for inflammation and oxidative stress in cardiovascular diseases, but evidence of the effects on lipid profile and glucose is still inconclusive. Therefore, we performed a meta-analysis to evaluate the efficacy of astaxanthin supplementation on plasma lipid and glucose concentrations. Material and methods: The search included PubMed, Cochrane Library, Scopus, and EMBASE (up to November 27, 2014) to identify randomized controlled trials (RCTs) investigating the effects of astaxanthin supplementation on lipid profile and glucose levels. Two independent reviewers extracted data on study characteristics, methods and outcomes. Results: Seven studies meeting inclusion criteria with 280 participants were selected for this meta-analysis; 163 participants were allocated to the astaxanthin supplementation group and 117 to the control group. A random-effect meta-analysis of data from 7 RCTs (10 treatment arms) did not show any significant effect of supplementation with astaxanthin on plasma concentrations of total cholesterol (weighted mean difference (WMD): -1.52 mg/dl, 95% CI: -8.69 to -5.66, p = 0.679), LDL-C (WMD: +1.25 mg/dl, 95% CI: -6.70 to +9.21, p = 0.758), HDL-C (WMD: +1.75 mg/dl, 95% CI: -0.92 to +4.42, p = 0.199), triglycerides (WMD: -4.76 mg/dl, 95% CI: -21.52 to +12.00, p = 0.578), or glucose (WMD: -2.65 mg/dl, 95% CI: -5.84 to +0.54, p = 0.103). All these effect sizes were robust, and omission of any of the included studies did not significantly change the overall estimate. Conclusions: This meta-analysis of data from 10 RCT arms did not indicate a significant effect of supplementation with astaxanthin on plasma lipid profile, but a slight glucose-lowering effect was observed. Further, well-designed trials are necessary to validate these results. [ABSTRACT FROM AUTHOR]