Oral Administration Of Antioxidants Research Articles

Targeted Therapy of Acute Liver Injury via Cryptotanshinone-Loaded Biomimetic Nanoparticles Derived from Mesenchymal Stromal Cells Driven by Homing.

Acute liver injury (ALI) has the potential to compromise hepatic function rapidly, with severe cases posing a considerable threat to human health and wellbeing. Conventional treatments, such as the oral administration of antioxidants, can inadvertently lead to liver toxicity and other unwanted side effects. Mesenchymal stromal cells (MSCs) can target therapeutic agents directly to inflammatory sites owing to their homing effect, and they offer a promising avenue for the treatment of ALI. However, the efficacy and feasibility of these live cell products are hampered by challenges associated with delivery pathways and safety concerns. Therefore, in this work, MSC membranes were ingeniously harnessed as protective shells to encapsulate synthesized PLGA nanoparticle cores (PLGA/MSCs). This strategic approach enabled nanoparticles to simulate endogenous substances and yielded a core-shell nano-biomimetic structure. The biomimetic nanocarrier remarkably maintained the homing ability of MSCs to inflammatory sites. In this study, cryptotanshinone (CPT)-loaded PLGA/MSCs (CPT@PLGA/MSC) were prepared. These nanoparticles can be effectively internalized by LO2 cells. They reduced cellular oxidative stress and elevated inflammatory levels. In vivo results suggested that, after intravenous administration, CPT@PLGA/MSCs significantly reduced uptake by the reticuloendothelial system and immune recognition compared to PLGA nanoparticles without MSC membrane coatings, subsequently resulting in their targeted and enhanced accumulation in the liver. The effectiveness of CPT@PLGA/MSCs in alleviating carbon tetrachloride-induced oxidative stress and inflammation in a mouse model was unequivocally demonstrated through comprehensive histological examination and liver function tests. This study introduces a pioneering strategy with substantial potential for ALI treatment.

Antioxidants-rich Nutraceutical Ameliorates Lead-induced Oxidative Stress in Albino Rats

Treatment of lead toxicity is usually through aggressive approach such as chelation and bowel irrigation and these therapies are used just to promote body metal excretion and are considered less effective due multiple limitations and side effects. Therefore, the present study was conducted to evaluate the protective and curative potentials of formulated antioxidant-rich nutraceutcals against lead-induced oxidative stress in albino rats. A total of Fifty (50) albino rats of both sexes weighing 200–220 g were equally and randomly divided into two (2) groups (A and B models) of twenty five rats each. The group A was designed to study the protective effect of formulated nutraceutical against lead-induce oxidative stress. While group B was to evaluate the curative effect of same formulated nutraceutical in rats after lead intoxication. The rats in each of the models were randomly divided into five groups. Thirty (20) rats of lead treated groups were administered with different concentration of antioxidant-rich nutraceutical in both models. While 10 rats were treated with standard drug. Our findings reveals that oral administration of antioxidant- rich supplement in lead-intoxicated rats (in both models) significantly reduced blood lead levels, increased the activity of antioxidants enzymes and glutathione levels. Similarly, the levels of antioxidant minerals (Fe, Zn, Cu and Se) and vitamins (A, C and E) were boosted significantly. Concurrently, significant decreased levels of malondialdehyde were observed after administration of the antioxidant-rich supplement, hence, lowering lead-induced oxidative stress. Therefore, oral administration of antioxidant-rich supplement may invariably use as protective and as well as curative regimen to curtail lead-induced oxidative stress.

The potential protective effect of melatonin and N-acetylcysteine alone and in combination on opioid-induced testicular dysfunction and degeneration in rat

Methadone (Met) is the most common treatment for opioid addiction. Although Met is effective for treatment of opioid dependence, sexual dysfunctions and infertility have been reported as a major problem in patients under Met treatment. The present study aimed to evaluate the effect of melatonin and N-acetylcysteine (N) on morphine and Met-induced oxidative stress, apoptosis, suppression of blood sexual hormones, impairment in sperm parameters, and sexual dysfunction. Adult male Wistar rats (n = 66) were randomly divided into 11 equal groups (n = 6) as follows: control, sham, morphine, Met, Met+N, Met+ melatonin, Met+melatonin+N, morphine+ Met, morphine+Met+ melatonin, morphine+Met+N, and morphine+Met+ melatonin+N groups. On day 56 post-treatment, the blood was collected from the tail and the serum levels of sex hormones were evaluated, then the rats were sacrificed, and their bilateral testes and epididymis were retrieved for histological, immunohistochemical, molecular, testicular tissue stress oxidative status, and sperm parameters assays. Exposure to morphine, Met, and shift of morphine to Met resulted in testicular degeneration that can be attributed to generating the stress oxidative-induced- apoptotic testicular cell death and impairing spermatogenesis. Melatonin and N alone and particularly, in combination with each other improved testicular degeneration, sex hormone suppression, and testicular function mediated by increasing the testicular antioxidant capacity and inhibition of the apoptosis pathway. It’s suggested that oral administration of antioxidants may be an effective treatment for attenuating some opioid-related testicular dysfunction and degeneration.

Sperm dna bridges versus genetic variability: an editorial

Sperm DNA fragmentation is recognized to compromise male fertility. The data entail that sperm DNA damage can be competently treated with oral antioxidant administration during a comparatively short time period. It is an understanding that the 2 types of DNA appear to be different and autonomously packaged molecules; though, research has demonstrated the interdependent nature of these conformations in contributing to male infertility. Data must endure to be congregated to establish strong associations between traditional semen analysis parameters and sperm DNA integrity; this information remnants controversial and useless in clinical practice until novel techniques for the diagnosis and treatment of sperm DNA can be established. More modern technology must be employed to correlate such information into valuable clinical awareness. This editorial is the collation of reports relating to research on sperm DNA biochemistry and molecular biology to establish an opinion revealing sperm DNA integrity likely to be both tremendously fragile and remarkably significant for male fertility.

O-272 Oral administration of antioxidants can support follicle survival in xenografted human ovarian tissue

Abstract Study question Can oral administration of antioxidants improve follicle survival in human ovarian tissue through reduction of oxidative stress in a xenotransplantation model? Summary answer Daily oral administration of antioxidants for 7 days post-transplantation had a positive effect on follicle survival in grafted human ovarian tissue. What is known already Today cryopreservation and autotransplantation of ovarian tissue is an established fertility preservation method in many centres. Hundreds of live births have been achieved but the efficacy of this procedure is hampered by a critical loss of follicles following transplantation. The ovarian tissue is subjected to hypoxia and ischemia postoperative which leads to oxidative damage in the tissue. Postoperative supplementation with antioxidants has been shown to decrease oxidative stress in transplanted ovarian tissue and increase follicle survival, however, these results were mainly obtained through intraperitoneal injections to host animals. Oral administration of antioxidants could be a better alternative for clinical application. Study design, size, duration Pieces of frozen-thawed ovarian cortex tissue (total of 56) from 12 women were transplanted to immunodeficient mice in a short- and long-term xenograft study, for 7 and 28 days respectively. In each study the mice were administered daily doses of hazelnut cream (control group) for 7 days post-transplantation or hazelnut cream containing either 150 mg/kg N-acetylcysteine (NAC) or FERTILIX (containing Vitamin E, D and C, Mixed Tocopherols and Tocotrienols, Lycopene, and Coenzyme Q10). Participants/materials, setting, methods Cryopreserved ovarian tissue was donated by 12 women undergoing ovarian tissue cryopreservation at Copenhagen University Hospital. Grafts were retrieved after 7 and 28 days of xenografting and histologically processed for follicle counts, immunohistochemistry, and qPCR analysis. The number of surviving follicles and ovarian graft volume were evaluated histologically after 7 and 28 days xenografting. Gene expression analysis of antioxidant defence markers (Sod1, Hmox and Catalase) and angiogenic factor Vegfa were performed after 7 days xenografting. Main results and the role of chance After 7 days xenografting, the follicle density was similar for all groups (control group: 33.03±14.85 (mean±SEM) follicles/mm3; NAC-group: 26.34±10.54 follicles/mm3, FERTILIX-group: 35.12±10.88 follicles/mm3). However, the NAC- and FERTILIX-group had a 3- and 3.7-fold increase in follicle density respectively compared to the control group. However, after 28 days of xenografting there was a higher density of surviving follicles in both antioxidant groups, compared to control (control group: 9.51±2.9 follicles/mm3; NAC-group: 14.9±6.02 follicles/mm3, FERTILIX-group: 14.43±5.83 follicles/mm3), which resulted in a 3.2-fold increase in follicle density in the NAC-group and 2.4-fold increase in the FERTILIX-group compared to the control group. The findings were not statistically significantly different in either the 7 days or 28 days study (p = 0.7072; p = 0.5691). The relative gene expression of the antioxidant defence genes Hmox and Catalase was overall like the control for all treatment groups after 7 days xenografting, but for Sod1 the expression was significantly lower for the NAC- and FERTILIX-group compared to the control group (p = 0.0407; p = 0.0255). For Vegfa the expression was similar overall and not significantly different from the control group (p > 0.05). Limitations, reasons for caution The distribution of follicles in human ovarian cortex is highly heterogeneous and can vary tremendously between cortex pieces from the same woman and between patients. Statistically significant results were not obtained for the follicle data in the current study; thus, the conclusions should be interpreted with caution. Wider implications of the findings Oral administration of antioxidants had a positive effect on follicle survival in xenotransplanted human ovarian tissue. These findings provide a step toward potential clinical administration of antioxidants like NAC or FERTILIX postoperative of ovarian tissue transplantation, which could improve follicle outcomes in a feasible way for the patient. Trial registration number Not applicable

An Ayurvedic approach in the management of vitreous floaters: A case report

Abstract: Vitreous floater is a commonly found eye condition in patients who complain of visualizing non-existing figures such as hair lines, black spots, and webs. Vitreous floaters are a sign of degeneration of vitreous gel, which if left untreated may cause severe irritation in the visual field of the patient. In modern science, floaters are treated with oral administration of antioxidants and pars plana vitrectomy surgeries. Conventional treatment options are not affordable to all patients and they may cause postoperative complications. These complications include moderate-to-severe pathophysiologies such as posterior vitreous detachment, traction retinal detachment, vitreous hemorrhage, macular edema, and full-thickness macular holes. A 56-year-old female patient who suffered from vitreous floaters was presented to Shalakya tantra outpatient department whose condition was managed by Ayurveda treatment approaches. The Triphala-yashti yoga was selected as a plan of treatment. The principle of treatment used in this study involves Ayurvedic medicines having an activity such as Chakshushya (~beneficial for eyes) to mitigate intravitreal oxidative stress, which has been linked to vitreous degeneration and associated symptoms. Changes in the symptoms were noted and the Short Floater Questionnaire score was reduced to 3.75/13 from 07/13 after three months of treatment. The utilization of a classical literature-based approach, combined with a methodology of identifying commonly mentioned botanicals within diverse mixtures, demonstrated favorable outcomes in the current study.

P1307: TESTING THE IMPORTANCE OF ANTIOXIDANTS ON THE PATHOGENESIS OF B CELL LYMPHOMA

Background: Our group found that antioxidant supplementation of the diet – in doses that reduce reactive oxygen species (ROS) levels – markedly accelerates progression and metastasis of malignant melanoma and lung cancer in mice. These findings can help explain the puzzling outcome of clinical trials with antioxidants and led to a heated debate about the safety of supplements for cancer patients. The findings, combined with those of dozens of clinical antioxidant trials, suggest that cancer patients and survivors should avoid antioxidant supplements. Although multiple other cancer types including breast, colon, and pancreatic cancer has been found to respond similarly to antioxidants, little is known about the effects in hematologic malignancies. In the latter, high doses of VitC – that increase oxidative stress – have shown therapeutic effects in some studies, including in B cell lymphoma. However, other studies have raised doubts about high-dose VitC therapy. Thus, many questions remain about the impact of antioxidant administration for B cell lymphoma progression, in particular in ROS-lowering doses. Aims: Define the impact of antioxidant administration on B cell lymphoma cell proliferation and viability in vitro and on the progression and survival of lymphoma in vivo. Methods: For in vitro experiment, we performed analyses of cell proliferation, cell cycle, apoptosis, and ROS levels; RNA from cells following interventions was isolated for RNAseq analysis; real-time PCR was performed to confirm candidate genes; and ChIP-qPCR to study protein-DNA binding. For in vivo experiments, we used xenograft models by subcutaneous injection of human B lymphoma cell lines, and used λMYC mice as a model of endogenous B cell lymphoma (these mice harbor a mutant human MYC gene controlled by a reconstructed Igλ locus). In vivo antioxidants were administered both orally in the drinking water, and was injected in different doses and combinations. Results: The antioxidants N-acetylcysteine (NAC), vitamin C (VitC), L-Cystein, and glutathione in doses that reduce ROS levels markedly reduced the viability of human B cell lymphoma cell lines in a MYC-dependent fashion. Intraperitoneal injections of NAC and VitC dose-dependently reduced tumor growth in xenograft experiments. Knockdown of MYC restored tumor growth in the presence of antioxidants and switching-on MYC expression in B cells rendered them sensitive to NAC and VitC. Molecular analyses revealed that antioxidants increased the binding of EGR1 to MYC and stimulated EGR1/MYC binding to apoptotic gene promotors—thus stimulating apoptosis. Intraperitoneal injections or life-long oral antioxidant administration reduced tumor growth and improved survival in λMYC transgenic mice. Summary/Conclusion: High MYC expression renders B lymphoma cells sensitive to therapy with common soluble antioxidants and indicates that this strategy might be useful—alone or in combination with lower doses of standard chemotherapy—in patients with MYC-driven lymphomas such as the diffuse large B cell variant.

Epimedium protects against dyszoospermia in mice with Pex3 knockout by exerting antioxidant effects and regulating the expression level of P16

Oxidative stress (OS) is one of the primary factors leading to male infertility. Oral administration of antioxidants has thus far been found to significantly improve the quality of human sperm. Therefore, antioxidant treatment has become the consensus among international experts on male infertility. In this study, peroxisomal biogenesis factor 3 (Pex3)-knockout (KO, −/−) mice were used as a model to compare the efficacy of three types of traditional Chinese medicine (TCM) granules (Epimedium [YYH], Cuscuta [TSZ], and Rhodiola [HJT]) for male reproductive function rescue. YYH was revealed to be the best and exerted a rescue effect on Pex3−/− mice with spermatogenesis defects. In addition, YYH prominently reduced ROS levels in the testes, inhibited DNA oxidative damage in spermatogenic cells, promoted the proliferation of spermatogenic cells, and inhibited apoptosis in Pex3−/− male mice. Furthermore, the mechanism by which YYH ameliorated dyszoospermia was confirmed via the establishment of cyclin-dependent kinase inhibitor 2 A (P16Ink4a)-KO mice. Specifically, Pex3−/− mice produced elevated amounts of ROS, which damaged germ cell DNA and further activated the signaling pathway of the cell senescence regulatory protein P16-CDK6, resulting in cell cycle arrest and eventually contributing to spermatogenesis dysfunction. YYH supplementation partially corrected the associated phenotype in gene KO mice by affecting P16 expression levels, thus improving the reproductive outcome to a certain extent.

Oral vitamin C restores endothelial function during acute inflammation in young and older adults.

Oxidative stress has been linked to reductions in vascular function during acute inflammation in young adults; however, the effect of acute inflammation on vascular function with aging is inconclusive. The aim of this study was to determine if oral antioxidant administration eliminates vascular dysfunction during acute inflammation in young and older adults. Brachial flow‐mediated dilation (FMD) and carotid‐femoral pulse wave velocity (PWV) were measured in nine young (3 male, 24 ± 4 yrs, 26.2 ± 4.9 kg/m2) and 16 older (13 male, 64 ± 5 yrs, 25.8 ± 3.2 kg/m2) adults before and 2‐h after oral consumption of 2 g of vitamin C. The vitamin C protocol was completed at rest and 24 h after acute inflammation was induced via the typhoid vaccine. Venous blood samples were taken to measure markers of inflammation and vitamin C. Both interleukin‐6 (Δ+0.7 ± 1.8 pg/ml) and C‐reactive protein (Δ+1.9 ± 3.1 mg/L) were increased at 24 h following the vaccine (p < 0.01). There was no change in FMD or PWV following vitamin C administration at rest (p > 0.05). FMD was lower in all groups during acute inflammation (Δ‐1.4 ± 1.9%, p < 0.01), with no changes in PWV (Δ‐0.0 ± 0.9 m/s, p > 0.05). Vitamin C restored FMD back to initial values in young and older adults during acute inflammation (Δ+1.0 ± 1.8%, p < 0.01) with no change in inflammatory markers or PWV (p > 0.05). In conclusion, oral vitamin C restored endothelial function during acute inflammation in young and older adults, with no effect on aortic stiffness. The effect of vitamin C on endothelial function did not appear to be due to reductions in inflammatory markers. The exact mechanisms should be further investigated.

Pathophysiological Association between Diabetes Mellitus and Endothelial Dysfunction.

Endothelial dysfunction plays a critical role in atherosclerosis progression, leading to cardiovascular complications. There are significant associations between diabetes mellitus, oxidative stress, and endothelial dysfunction. Oxidative stress is increased by chronic hyperglycemia and acute glucose fluctuations induced by postprandial hyperglycemia in patients with diabetes mellitus. In addition, selective insulin resistance in the phosphoinositide 3-kinase/Akt/endothelial nitric oxide (NO) synthase pathway in endothelial cells is involved in decreased NO production and increased endothelin-1 production from the endothelium, resulting in endothelial dysfunction. In a clinical setting, selecting an appropriate therapeutic intervention that improves or augments endothelial function is important for preventing diabetic vascular complications. Hypoglycemic drugs that reduce glucose fluctuations by decreasing the postprandial rise in blood glucose levels, such as glinides, α-glucosidase inhibitors and dipeptidyl peptidase 4 inhibitors, and hypoglycemic drugs that ameliorate insulin sensitivity, such as thiazolidinediones and metformin, are expected to improve or augment endothelial function in patients with diabetes. Glucagon-like peptide 1 receptor agonists, metformin, and sodium-glucose cotransporter 2 inhibitors may improve endothelial function through multiple mechanisms, some of which are independent of glucose control or insulin signaling. Oral administration of antioxidants is not recommended in patients with diabetes due to the lack of evidence for the efficacy against diabetic complications.

D-galactose: a model of accelerated ageing sufficiently sensitive to reflect preventative efficacy of an antioxidant treatment.

Considering that the phenomenon of accelerated ageing contributes to early onset of various chronic diseases, modelling of the relevant dysregulated systems or responses is vital for research aimed at identification of potential therapeutic targets. Here, we aimed to establish a model capable of simulating the redox and inflammatory changes of accelerated ageing-specifically, the aim was early phase accelerated ageing, which would allow therapeutic intervention in a preventative approach prior to clinical disease manifestation. A secondary aim was to evaluate the sensitivity of the model to reflect preventative treatment efficacy. Daily D-galactose injections (250mg/kg body mass/day) for 8weeks in 9-week-old male Wistar rats induced a model of early accelerated ageing (decreased plasma FRAP; P < 0.05 and altered inflammatory signalling) and an aged profile in lymph node ultrastructure, but did not yet result in telomere shortening. Preventative daily oral antioxidant administration (grape seed-derived polyphenol, 100mg/kg body mass) prevented tissue ageing, beneficially modulated the inflammatory response, including neutrophil chemokinetic capacity, and tended to increase absolute telomere length. Data suggests that using a mild model of D-galactose administration than those employed to induce neurodegeneration, simulated the point where oxidative stress starts to overwhelm the endogenous antioxidant response and where a pro-inflammatory phenotype switch manifests. Furthermore, despite the expected small effect size, the model was sufficiently sensitive to reflect benefits of preventative antioxidant treatment in the context of ageing. This model presents a practical model for use in drug discovery, particularly in the context of preventative medicine aimed at limiting oxidative stress-associated ageing. Since this starting point of accelerated ageing as illustrated by current data, is not expected to reflect major ageing-associated changes yet, we recommend that future preventative drug discovery studies employ a longitudinal study design in order to clearly demonstrate the delay of this starting point by preventative strategies.

Chronic antioxidant administration restores macrovascular function in patients with heart failure with reduced ejection fraction.

What is the central question of this study? We aimed to examine oxidative stress, antioxidant capacity and macro- and microvascular function in response to 30 days of oral antioxidant administration in patients with heart failure with reduced ejection fraction. What is the main finding and its importance? We observed an approximately twofold improvement in macrovascular function, assessed via brachial artery flow-mediated dilatation, and a reduction in oxidative stress after antioxidant administration in patients with heart failure with reduced ejection fraction. The improvement in macrovascular function was reversed 1week after treatment cessation. These findings have identified the potential of oral antioxidant administration to optimize macrovascular health in this patient group. Heart failure with reduced ejection fraction (HFrEF) is characterized by macrovascular dysfunction and elevated oxidative stress that may be mitigated by antioxidant (AOx) administration. In this prospective study, we assessed flow-mediated dilatation (FMD) and reactive hyperaemia responses in 14 healthy, older control participants and 14 patients with HFrEF, followed by 30days of oral AOx administration (1g vitaminC, 600I.U. vitaminE and 0.6g α-lipoic acid) in the patient group. Blood biomarkers of oxidative stress (malondialdehyde) and AOx capacity (ferric reducing ability of plasma) were also assessed. Patients with HFrEF had a lower %FMD (2.63±1.57%) than control participants (5.62±2.60%), and AOx administration improved %FMD in patients with HFrEF (30days, 4.90±2.38%), effectively restoring macrovascular function to that of control participants. In a subset of patients, we observed a progressive improvement in %FMD across the treatment period (2.62±1.62, 4.23±2.69, 4.33±2.24 and 4.97±2.56% at days 0, 10, 20 and 30, respectively, n=12) that was abolished 7days after treatment cessation (2.99±1.78%, n=9). No difference in reactive hyperaemia was evident between groups or as a consequence of the AOx treatment. Ferric reducing ability of plasma levels increased (from 6.08±2.80 to 6.70±1.59mm, day0versus 30) and malondialdehyde levels decreased (from 6.81±2.80 to 6.22±2.84μm, day 0versus 30) after treatment. These findings demonstrate the efficacy of chronic AOx administration in attenuating oxidative stress, improving AOx capacity and restoring macrovascular function in patients with HFrEF.

Bacterioruberin from Haloarchaea plus dexamethasone in ultra-small macrophage-targeted nanoparticles as potential intestinal repairing agent

Oral administration of antioxidant and anti-inflammatory drugs have the potential to improve the current therapy of inflammatory bowel disease. Success of oral treatments, however, depends on the capacity of drugs to remain structurally stable along the gastrointestinal tract, and on the feasibility of accessing the target cells. Delivering anti-inflammatory and antioxidant drugs to macrophages using targeted nanoparticles, could make treatments more efficient. In this work structural features and in vitro activity of macrophage-targeted nanostructured archaeolipid carriers (NAC) containing the high antioxidant dipolar C50 carotenoid bacterioruberin (BR) plus dexamethasone (Dex): NAC-Dex, are described. Ultra-small (66 nm), −32 mV ζ potential, 1200 μg Dex /ml NAC-Dex, consisted of a compritol and BR core, covered by a shell of sn 2,3 ether linked archaeolipids and Tween 80 (2: 2: 1.2: 3 % w/w) were obtained. NAC-Dex were extensively captured by macrophages and Caco-2 cells and displayed high anti-inflammatory and antioxidant activities on a gut inflammation model made of Caco-2 cells and lipopolysaccharide stimulated THP-1 derived macrophages reducing 65 % and 55 % TNF-α and IL-8 release, respectively and 60 % reactive oxygen species production. NAC-Dex also reversed the morphological changes induced by inflammation and increased the transepithelial electrical resistance, partly reconstituting the barrier function. Activity of BR and Dex in NAC-Dex was partially protected after simulated gastrointestinal digestion, improving the chances of BR-Dex joint activity. Results suggest that oral NAC-Dex deserve further exploration as intestinal barrier repairing agent.

Response to exercise in older adults who take supplements of antioxidants and/or omega-3 polyunsaturated fatty acids: A systematic review

BackgroundNutrition is a key factor in determining exercise response. The aim of this review is to assess the response to exercise in older adults who take supplements of antioxidants and/or omega-3 polyunsaturated fatty acids. MethodsA systematic literature search was performed (June 2009- September 2019) in MEDLINE via Pubmed. The following search strategy was used with Boolean markers: (“omega-3 fatty acids” [Major] OR “antioxidants” [Major]) AND “exercise” AND “aged” [MesH]. Fourteen articles were finally included. ResultsExercise-induced free radical and inflammatory marker blood levels, but not changed the plasma total antioxidant capacity (TAC), after administration of antioxidant supplement. The oral administration of antioxidants produced null or negative effect on endothelial function, but the infusion into the brachial artery during rhythmic handgrip exercise produced a significant improvement in muscle blood flow, due to an on increase in the availability of nitric acid derived from the nitric oxide synthase. Aerobic exercise and antioxidant supplementation improved submaximal and maximal aerobic parameters, as well as mitochondrial density and mitochondria-regulated apoptotic signaling. Antioxidant supplementation, but not omega-3 PUFA, decreased pro-inflammatory marker levels and fat oxidation induced by exercise. Strength training decreased serum B12 concentration but combined with omega-3 PUFA or antioxidant supplementation, B12 levels were maintained. Antioxidant supplementation has protective effect after fatigue in isometric exercise but improved appendicular fat-free mass just combined with resistance exercise. Omega-3 fatty acid supplement combined with exercise increased lean mass in women, but not in men. Muscle damage induced by exercise is protected by antioxidant supplementation. ConclusionsOlder people who take antioxidant and/or omega-3 PUFA supplements showed improved exercise response, as well as lower muscle damage.

The effects of antioxidants on ocular blood flow in patients with glaucoma.

To investigate the effects of an antioxidant dietary supplement that includes Ginkgo biloba, on retinal and retrobulbar blood flow in patients with open-angle glaucoma (OAG). Forty-five patients with confirmed OAG were enroled in a randomized, double blinded, placebo-controlled cross-over study. Baseline and postadministration measurements of intraocular pressure (IOP), ocular perfusion pressure (OPP), retrobulbar blood flow, and retinal capillary blood flow were non-invasively measured (ultrasound and laser Doppler modalities, respectively) before and one month after antioxidant nutraceuticals and placebo administration. Changes in measurements between the active supplement and placebo arms were evaluated using paired t-tests, with p<0.05 considered statistically significant. Antioxidant supplementation produced a statistically significant increase in peak systolic and/or end diastolic blood flow velocities in all retrobulbar blood vessels compared to placebo. Vascular resistance was also reduced in central retinal and nasal short posterior ciliary arteries following antioxidant administration. Additionally, antioxidant supplementation increased superior and inferior temporal retinal capillary mean blood flow and the ratio of active to non-active retina capillaries compared to placebo. One-month oral administration of antioxidants produced increases in biomarkers of ocular blood flow within retinal and retrobulbar vascular beds in patients with OAG.

Oral administration of antioxidants improves skin wound healing in diabetic mice.

Oxidative stress aggravates several long-term complications in diabetes mellitus. We evaluated the effectiveness of the oral administration of antioxidants (vitamins E and C, 40 and 100 mg/kg b.w., respectively) on skin wound healing acceleration in alloxan-induced diabetic mice. Mice were wounded 30 days after the induction of diabetes. Antioxidants were effective in preventing oxidative stress, as assessed by TBARS. The enzymes catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were increased in diabetics on the 3rd day post-wounding; catalase and glutathione peroxidase remained still augmented in diabetics after 14th day postwounding, and the treatment with vitamins restored their activities to control. After 3 days, diabetic mice showed lower infiltration of inflammatory cells (including CD11b+ and Ly6G+ cells) and reduced levels of KC, TNF-α, IL-1β, and IL-12 p40 when compared with control mice. The treatment restored cytokine levels. After 14 days, diabetic mice showed late wound closure, persistent inflammation and delayed reepithelialization, accompanied by an increase in MIG+ /CD206- macrophages whereas CD206+ /MIG- macrophages were decreased. Cytokines IL-12p40, TNF-α, IL-1β, and KC were increased and normal levels were restored after treatment with antioxidants. These results suggest that oxidative stress plays a major role in diabetic wound healing impairment and the oral administration of antioxidants improves healing by modulating inflammation and the antioxidant system with no effect on glycemia.

Nanoparticles based on quaternary ammonium–chitosan conjugate: A vehicle for oral administration of antioxidants contained in red grapes

The purpose of this study was to demonstrate that nanoparticles (NP), obtained by ionotropic crosslinking of reduced-MW chitosan (rCh) derivatives with reduced-MW hyaluronan (rHA), could be profitable vehicles for oral administration of beneficial doses of antioxidant constituents of red grape seeds extracts (GSE). NP have previously shown aptitude for internalisation by endothelial progenitor cells. Here they were seen by a fluorescence microscope migrating across excised rat intestine from mucosal to serosal side and permeating from the donor to the acceptor compartment of an Ussing chamber while carrying significant (15–20%) steadily associated fractions of initial antioxidant load. Freshly prepared NP dispersions were stabilised by lyophilisation. The NP dispersions were regenerated from the lyophilised products by adding water under gentle stirring. Lyophilisation-regeneration caused a significant NP size increase yet particles did not grow beyond the upper size limit of particles able to cross the intestinal barrier (500 nm).

Treatment with zinc, d-aspartate, and coenzyme Q10 protects bull sperm against damage and improves their ability to support embryo development

Reactive oxygen species (ROS) are physiologically generated during mitochondrial respiration and are involved in several signaling mechanisms. However, under pathological conditions, the concentration of ROS may exceed the antioxidant scavenging systems and subsequently lead to cell damage. High ROS levels have been proven to be detrimental to spermatozoa and furthermore compromise sperm function through lipid peroxidation, protein damage, and DNA strand breakage. Although the oral administration of antioxidants has been demonstrated to improve the semen quality in subfertile men, it is still a matter of debate if it can positively influence fertilization outcome and embryo developmental competence. Studies carried out in suitable animal models could resolve these fundamental questions. Hence, the main aims of the present study were to evaluate: (1) the effects of zinc, d-aspartate, and coenzyme Q10, included in the dietary supplement Genadis (Merck Serono), on bull sperm motility and DNA fragmentation; and (2) whether treated spermatozoa have a superior competence in fertilization and in supporting the development of healthy embryos. Our data indicate that this treatment prevents the loss of sperm motility and the rise in sperm DNA fragmentation over time. Moreover, blastocyst rate was found to be significantly higher in oocytes fertilized by treated spermatozoa, and these blastocysts harbored a significantly lower percentage of apoptotic cells.

In serum veritas—in serum sanitas? Cell non-autonomous aging compromises differentiation and survival of mesenchymal stromal cells via the oxidative stress pathway

Even tissues capable of complete regeneration, such as bone, show an age-related reduction in their healing capacity. Here, we hypothesized that this decline is primarily due to cell non-autonomous (extrinsic) aging mediated by the systemic environment. We demonstrate that culture of mesenchymal stromal cells (MSCs) in serum from aged Sprague–Dawley rats negatively affects their survival and differentiation ability. Proteome analysis and further cellular investigations strongly suggest that serum from aged animals not only changes expression of proteins related to mitochondria, unfolded protein binding or involved in stress responses, it also significantly enhances intracellular reactive oxygen species production and leads to the accumulation of oxidatively damaged proteins. Conversely, reduction of oxidative stress levels in vitro markedly improved MSC function. These results were validated in an in vivo model of compromised bone healing, which demonstrated significant increase regeneration in aged animals following oral antioxidant administration. These observations indicate the high impact of extrinsic aging on cellular functions and the process of endogenous (bone) regeneration. Thus, addressing the cell environment by, for example, systemic antioxidant treatment is a promising approach to enhance tissue regeneration and to regain cellular function especially in elderly patients.

Dextran-Functionalized Magnetic Fluid Mediating Magnetohyperthermia Combined with Preventive Antioxidant Pequi-Oil Supplementation: Potential Use Against Cancer

This work aimed to test a dextran-functionalized magnetic fluid (DexMF) sample in mediating magnetohyperthermia to treat an advanced clinical Ehrlich-solid-tumor, to verify the effects of oral antioxidant administration of pequi-oil on this treatment and to investigate the potential of these treatments for future use as an adjuvant in cancer therapy. Animals received the treatments: (a) filtered water (control); (b) tumor implantation and no treatment (tumor group); (c) tumor implantation followed by intratumoral injection of DexMF and alternating current magnetic field exposure (MHT group) for three consecutive days; (d) oral pequi-oil supplementation followed by tumor implantation and the same treatment as group MHT (PMHT group). Analyses took place 1 and 2 weeks after tumor implantation. Both treatments were effective in increasing the tumor necrosis process and controlling tumor growth, besides keeping lymphocyte-dependent immunity. Although the MHT treatment was more efficient after the first week in reducing DNA damage to blood peripheral leucocytes, PMHT therapy appeared to be more effective with the advance of the carcinogenesis process after the second week. Our findings evidence the potential use of DexMF mediating magnetohyperthermia in cancer treatment and also suggest that the preventive pequi oil administration could increase the efficiency of this process.