Combined Antioxidant Therapy Research Articles

Оценка эффективности и безопасности применения антиоксидантного комплекса «Спермаферт»

Reactive oxygen species negatively affect the indicators of ejaculate and spermatogenesis in general. This study evaluated the efficacy and safety of combination antioxidant therapy with respect to the treatment of male infertility. The general indicators of the ejaculate and the sperm DNA fragmentation index were assessed. Men with a high sperm DNA fragmentation index were recommended to take 1 capsule and 5 ml of liquid (1 scoop) once a day with meals. The liquid contains L-carnitine – 900 mg; 1 capsule contains: lipoic acid - 96 mg, vitamin C – 72 mg, zinc citrate – 56 mg, vitamin B6 – 2.4 mg, folic acid – 0.48 mg, 9-phenyl-symmetric octahydroselenoxanthene – 0.34 mg. Results. After three months of treatment with the antioxidant complex "Spermafert", ejaculate valuesimproved, as evidenced by a decrease in the sperm DNA fragmentation index from 21.6 ± 3.2% to 12.8 ± 3.3%; an increase in sperm concentration from 29.7× 106 /ml to 35.7 × 106 /ml an increase in the totalsperm count from 72.1 × 106 to 95.5 × 106 . Findings. Taking antioxidants can improve overall ejaculate counts and lowersperm DNA fragmentation index levelsin men in infertile marriages. The conclusions of thisstudy coincide with general trendsin this direction. Keywords: male infertility, antioxidants, Spermafert, DNA fragmentation

ПРИМЕНЕНИЕ МЕМБРАНОПРОТЕКТОРОВ ДЛЯ ЛЕЧЕНИЯ ПАЦИЕНТОВ С "МОЛНИЕНОСНОЙ" ФОРМОЙ ОСТРОГО ПАНКРЕАТИТА

Background Acute pancreatitis, which causes a huge number of complications, has been and remains one of the most serious diseases in urgent surgery. Despite the currently existing algorithms for the diagnosis and treatment of acute pancreatitis, a number of unresolved issues remain that require further studying. Purpose. To substantiate the effectiveness of the use of membrane protectors in the complex treatment of acute pancreatitis. Material and methods. The retrospective stage (2016–2018) included 30 patients diagnosed with acute pancreatitis who received standard treatment. The prospective stage (2018–2020) included 31 patients diagnosed with acute pancreatitis (AP). In addition to the complex treatment for these patiets, membrane protectors were used in the pre- and postoperative period. The groups were comparable in age and extent of the pancreatic lesion. During the study, in addition to the standard surgical treatment, the patients received the drug “Neurox” in the pre- and postoperative period. Results. The use of membrane protectors is justified, on day 14 there was a statistical decrease in erythrocyte membrane ruptures. Discussion. In recent years, there has been an increase in the number of studies investigating the effect of membrane protective therapy on the course of acute pancreatitis in general, and destructive forms in particular.Some publications note the effectiveness of combined membrane protective and antioxidant therapy in destructive pancreatitis. Conclusion. The use of membrane protectors in the complex treatment of acute pancreatitis is pathogenetically justified and can be used for the therapeutic correction of acute pancreatitis, taking into account the developing morphofunctional processes.

Safety and Pharmacokinetics of a Combined Antioxidant Therapy against Myocardial Reperfusion Injury: A Phase1 Randomized Clinical Trial in Healthy Humans.

Myocardial reperfusion injury (MRI) accounts for up to 50% of the final size in acute myocardial infarction and other conditions associated with ischemia-reperfusion. Currently, there is still no therapy to prevent MRI, but it is well known that oxidative stress has a key role in its mechanism. We previously reduced MRI in rats through a combined antioxidant therapy (CAT) of ascorbic acid, N-acetylcysteine, and deferoxamine. This study determines the safety and pharmacokinetics of CAT in a Phase I clinical trial. Healthy subjects (n = 18) were randomized 2:1 to CAT or placebo (NaCl 0.9% i.v.). Two different doses/infusion rates of CATs were tested in a single 90-minute intravenous infusion. Blood samples were collected at specific times for 180 minutes to measure plasma drug concentrations (ascorbic acid, N-acetylcysteine, and deferoxamine) and oxidative stress biomarkers. Adverse events were registered during infusion and followed for 30 days. Both CAT1 and CAT2 significantly increased the CAT drug concentrations compared to placebo (P < .05). Most of the pharmacokinetic parameters were similar between CAT1 and CAT2. In total, 6 adverse events were reported, all nonserious and observed in CAT1. The ferric-reducing ability of plasma (an antioxidant biomarker) increased in both CAT groups compared to placebo (P < .001). The CAT is safe in humans and a potential treatment for patients with acute myocardial infarction undergoing reperfusion therapy.

Combined antioxidant therapy against reperfusion injury in acute myocardial infarction: preclinical drug development and phase I clinical trial in humans

Combined antioxidant therapy against reperfusion injury in acute myocardial infarction: preclinical drug development and phase I clinical trial in humans

Reduction in Arterial Stiffness Index (SI) in Response to Combination Antioxidant Therapy.

Antioxidants reduce arterial stiffness, but the effects previously reported are weak. A systematic review of the antioxidants vitamin E, vitamin C, vitamin A, and beta-carotenes (the most commonly studied antioxidants) on pulse wave velocity (PWV) found an effect size of only -0.20 (approximately -16 m/s or -2.5%). Studies in rats of the potent pro-oxidant substance acetaldehyde have shown that combinations of sulfur-containing antioxidants, including thiamine and l-cysteine, with ascorbic acid potently protect against oxidative-stress-mediated mortality. The effects of these combinations of oxidants on PWV have not been studied. The present study evaluated the effects of 2 weeks of therapy with a combination of sulfur-containing antioxidants (cysteine, thiamine, and pyridoxine) in combination with ascorbic acid on stiffness index (SI), a measure of arterial stiffness that is strongly correlated with PWV, using a Pulse Trace recorder in a diverse group of 78 volunteers. SI fell by -1.7 m/s relative to placebo (95% confidence intervals -0.6 to -2.7 m/s), a reduction of -19% (95% confidence intervals -9% to -31%). The Glass effect size was 1.4, indicating a very strong treatment effect which was substantially greater than the effect size found in previous studies of antioxidants. PWV reduction was correlated significantly with increasing age. Further studies of similar antioxidant combinations are required to determine whether they are of value in the treatment or prevention of cardiovascular disease.

Micronutrient supplements as antioxidants in improving sperm quality and reducing DNA fragmentation

BackgroundSpermatogenesis and sperm quality may be negatively impacted by an increase in reactive oxygen species. This study investigates the efficacy of combined antioxidant therapy for treating male infertility, as measured by semen analyses and the sperm DNA fragmentation index (DFI). Infertile men with a high sperm DNA fragmentation index were instructed to take two oral micronutrient capsules daily for three months. Each antioxidant formulation contained 60 mg vitamin E, 400 µg folic acid, 30 mg selenium, 125 mg L-arginine, 220 mg L-carnitine, 7.5 mg coenzyme Q10, 40 mg L-glutathione, and 20 mg zinc citrate. At entry and post-treatment, the general characteristics, semen analysis, and sperm chromatin dispersion assays were recorded and compared.ResultsAfter three months of treatment with antioxidant compounds, the quality of spermatozoa improved significantly, as indicated by a decrease in the mean DNA fragmentation index from 45.6 ± 17.2% to 34.8 ± 20.3%; an increase in sperm concentration from 29.7 × 106/mL to 35.7 × 106/mL (p < 0.001), an increase in a total number of spermatozoa from 72.1 × 106 to 95.5 × 106 (p = 0.012), and an increase in the vitality from 75.5 ± 17.1 to 81.1 ± 14.4% viable forms (p < 0.001).ConclusionsMicronutrient supplementation can improve sperm quality and DNA integrity in infertile men. Men with infertility and significant sperm DNA fragmentation who take antioxidants for three months experience a reduction in DNA fragmentation index and an increase in sperm quality as measured by the semen analysis.Trial registrationNCT04509583. Registered 12 August 2020, Hue University of Medicine and Pharmacy Ethics Committee—Retrospectively registered.

Effect of combined antioxidant and photodynamic therapy on the emotional state of patients with vulvar craurosis

Objective: studying of the effect of combined antioxidant and photodynamic therapy (PDT) on the emotional state of patients with vulvar kraurosis. Materials and methods: the study involved 90 women with vulvar kraurosis who were randomized into three groups of 30 participants. In the first group, treatment included photodynamic therapy (PDT) followed by administration of the antioxidant Ethylmethylhydroxypyridine succinate for one month. Participants in the second group received only PDT. Patients of the third group underwent a course of laser therapy on the perineal region. The emotional state of the participants was assessed using the Hospital Anxiety and Depression Scale (HADS) before and at the end of treatment, 1, 6 and 12 months after the end of therapy. Results: before treatment, participants from the three groups scored a similar number of HADS scores. In the course of observations, the best result on the scales of anxiety and depression was recorded in patients who received combined antioxidant and photodynamic therapy. After a month of taking Ethylmethylhydroxypyridine succinate, the HADS score in these women was significantly lower than in the comparison groups. Further, these patients continued to show better scores on the depression scale. The total scores on the anxiety scale in this group were comparable to those in patients who received only PDT. Conclusion: combined antioxidant and photodynamic therapy, including Ethylmethylhydroxypyridine succinate, has a more pronounced positive effect on the emotional background of patients with vulvar kraurosis in comparison with PDT and laser therapy.

The Combined Treatment of Glutathione Sodium Salt and Ascorbic Acid for Preventing Contrast-Associated Acute Kidney Injury in ST-Elevation Myocardial Infarction Patients Undergoing Primary PCI: A Hypothesis to Be Validated.

The occurrence of Contrast-Associated Acute Kidney Injury (CA-AKI) in patients with ST-Elevation Myocardial Infarction (STEMI) has a negative impact on the length of hospital stay and mortality. Reactive Oxygen Species (ROS) release, along with vasoconstriction and hypoperfusion, play a key role in its development. To date, there is still no validated prophylactic therapy for this disease. The use of antioxidants, based on experimental and clinical studies, looks promising. Taking into consideration previous literature, we speculate that an early, combined and prolonged intravenous administration of both Glutathione (GSH) and ascorbic acid in STEMI patients undergoing primary Percutaneous Coronary Intervention (pPCI) may be of value in counteracting the occurrence of CA-AKI. We aimed at evaluating this hypothesis by applying a multicenter research protocol, using a double-blind randomized, placebo-controlled trial design. The primary endpoint will be to test the efficacy of this combined antioxidant therapy in reducing the occurrence of renal damage, in patients with acute myocardial infarction treated with pPCI. Furthermore, we will investigate the effect of the study compounds on changes in oxidative stress markers and platelet activation levels through bio-humoral analyses.

Влияние применения комбинированной антиоксидантной терапии на результаты эндоваскулярного лечения пациентов с облитерирующим атеросклерозом артерий нижних конечностей

INTRODUCTION: The number of endovascular interventions performed on the arteries of the lower extremities is growing annually in the world, as they provide faster patient recovery and shorten the period of hospital stay. However, the development of restenosis of the reconstruction zone often leads to a need for repeated operations. AIM: To evaluate the effectiveness of combined antioxidant therapy in reducing the risk of restenosis after endovascular interventions. MATERIALS AND METHODS: The study included 84 patients with IIB–III stage peripheral arterial disease (PAD). Group A included 45 patients who underwent endovascular interventions, group B included 39 patients who were prescribed combined antioxidant therapy (Vitamin E, Actovegin®) a week before endovascular intervention and within a week after. On admission to hospital, in the first hours of stay, in 1, 7 days after surgery, the amount of Bax and platelet growth factor (PDGF BB) biomarkers were determined in the blood serum of all the patients. On control visits, the patients underwent duplex scanning of the arteries of the lower extremities to measure the thickness of the neointima and to detect restenosis of the intervention area. RESULTS: When comparing Bax values in the first hours and days after surgery in groups A and B, its growth was noted in patients of the first group (p &lt; 0.01). At the same time, in patients of group A, the increase in PDGF BB was more pronounced (p &lt; 0.01) on the 7th day. In patients of group A with restenosis of the reconstruction zone, the values of Bax marker in the first hours after surgery exceeded those in patients of group B (р &lt; 0.01). On the 7th day, the amount of PDGF BB in these patients of group A was increased relative to group B (р &lt; 0.01). The changes in the number and dynamics of the studied markers in group B patients with restenosis of the reconstruction zone led, firstly, to decrease in the percentage of stenosis in the area of the previous surgical intervention, secondly, to decrease in the severity of the clinical manifestation of this complication, thirdly, to occurrence of restenosis of the reconstruction zone in the later period, and, fourthly, to decrease in the percentage of patients with this complication. CONCLUSION: The use of combined antioxidant therapy targeted at the system of apoptosis, can reduce the thickness of the neointima of the reconstruction zone and reduce the percentage of patients with restenosis after endovascular interventions.

A comparative study of lipid-based drug delivery systems with different microstructure for combined dermal administration of antioxidant vitamins

Antioxidant vitamins have been proven to be highly efficient in treatment of skin impaired by oxidative stress, but challenges regarding stability and skin penetration limit their therapeutic effect. Lipid-based drug delivery systems offer great potential for overcoming these drawbacks. This work aimed to identify the most promising system for combined antioxidant therapy. A comparative assessment of several systems, containing the same ingredients but differing in their microstructure, was therefore performed. Namely, microemulsions (MEs) of both types (W/O and O/W) and lyotropic liquid crystals (LLCs), simultaneously loaded with vitamin C or ascorbyl palmitate and vitamin E, were assessed. Stability, antioxidant capacity (DPPH assay), and release (Franz diffusion cells) of the vitamins incorporated was examined. The results obtained were supported with the systems’ thermal and rheological (rotational and oscillatory tests) evaluation. In addition, biological acceptability (MTS assay) of the systems studied was investigated. The findings demonstrate that the microstructure of MEs and LLCs studied has a decisive impact on the stability, antioxidant activity, and release of the vitamins incorporated. The highest stability was preserved in LLCs for both pairings, with vitamins C and E being a more stable combination. LLCs also provided suitable vitamins’ antioxidant activity and release characteristics. In addition, the system exhibited preferable rheological features for dermal administration. Furthermore, cytotoxicity studies on a keratinocyte cell line demonstrated the highest biocompatibility for LCCs with the cell proliferation being greater than 85%. In conclusion, LLCs were confirmed as the most favorable lipid-based drug delivery system for combined antioxidant treatment.

Naturally Occurring Antioxidant Therapy in Alzheimer's Disease.

It is estimated that the prevalence rate of Alzheimer’s disease (AD) will double by the year 2040. Although currently available treatments help with symptom management, they do not prevent, delay the progression of, or cure the disease. Interestingly, a shared characteristic of AD and other neurodegenerative diseases and disorders is oxidative stress. Despite profound evidence supporting the role of oxidative stress in the pathogenesis and progression of AD, none of the currently available treatment options address oxidative stress. Recently, attention has been placed on the use of antioxidants to mitigate the effects of oxidative stress in the central nervous system. In preclinical studies utilizing cellular and animal models, natural antioxidants showed therapeutic promise when administered alone or in combination with other compounds. More recently, the concept of combination antioxidant therapy has been explored as a novel approach to preventing and treating neurodegenerative conditions that present with oxidative stress as a contributing factor. In this review, the relationship between oxidative stress and AD pathology and the neuroprotective role of natural antioxidants from natural sources are discussed. Additionally, the therapeutic potential of natural antioxidants as preventatives and/or treatment for AD is examined, with special attention paid to natural antioxidant combinations and conjugates that are currently being investigated in human clinical trials.

Efficacy of combined antioxidant therapy in male subfertility-A systematic review and meta-analysis.

Antioxidant therapy is a potentially promising approach to improve clinical outcomes for couples undergoing assisted reproduction techniques long-term. The review aims to (a) collate evidence for the effectiveness of combined oral antioxidant supplementation, including a head-to-head comparison in the treatment of male subfertility, and (b) investigate whether other intervention features, including duration, specific combinations, or dosage affect clinical outcomes in this population. Randomized controlled trials (RCTs) that examined the effectiveness of combined antioxidants on male subfertility, electronic databases including PubMed, Embase, CINAHL, PSYCHINFO, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched. We also searched for unpublished data and references of identified articles. Two reviewers screened eligible studies according to pre-defined criteria and relevant data extracted. The Jadad scale assessed the quality of studies. The study used RevMan version 5.4.1 Meta-analysis software to analyze the effect of combination antioxidants for each outcome measure. Metadata was presented as relative risks for dichotomous outcomes and as standardized mean differences (or mean differences) for continuous outcomes. The systematic review and meta-analysis aimed to report available evidence of whether combination antioxidant is effective and safe in sub-fertile men undergoing assisted reproductive techniques. Also, this review highlighted whether any specific oral antioxidant combinations, dosage, or duration of therapy have a major influence on the clinical outcomes.

Nephroprotective Effect of Coenzyme Q10 alone and in Combination with N-acetylcysteine in Diabetic Nephropathy

Abstract Aim Oxidative stress due to chronic hyperglycaemia is a key factor in the development and progression of various microvascular complications including diabetic nephropathy (DN) and associated renal injury. Treatment with antioxidants is one of the strategies to protect the kidney from oxidative tissue damage to improve renal physiology during DN. The investigation, therefore, was designed to assess the nephroprotective effect of coenzyme Q10 (CoQ10) and N-acetylcysteine (NAC), either alone or in combination in streptozotocin (STZ)-nicotinamide (NAD) induced diabetic nephropathy (DN) in rats. Methods T2DM induced by STZ (55 mg/kg, i.p.)-NAD (110 mg/kg, i.p.) in Sprague-Dawley rats (220–250 g) was confirmed by the elevated blood glucose level and glycated haemoglobin. DN was assessed by renal function tests. The diabetic rats were treated with CoQ10 (10 mg/kg, p.o.) and/or NAC (300 mg/kg, p.o.) for 8 weeks after confirmation of DN. Oxidative tissue damage due to STZ-NAD was estimated by malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH), myeloperoxidase (MPO) and nitric oxide (NO) in the renal homogenate. Results Data showed significant alteration in serum and urinary creatinine, total protein, albumin, serum urea, blood urea nitrogen (BUN) and uric acid in diabetic animals as compared to the control rats. CoQ10 and/or NAC effectively alleviated the disturbances in renal function. Diabetic rats showed increased MDA, decreased SOD and CAT activities and decreased GSH along with a significant increase in MPO activity and nitrite content. Treatment with the aforementioned antioxidants and their combination ameliorated the kidney damage as indicated by the reduced OS with improved renal function. Conclusion The investigation suggests that the chronic hyperglycaemia-induced OS leads to the development and progression of DN. The combined treatment with CoQ10 and NAC has shown a remarkable nephroprotective effect suggesting that combined antioxidant therapy with CoQ10 and NAC may be useful in the attenuation of DN.

Analysis of efficacy of combined therapy of amyotrophic lateral sclerosis in mSOD1 transgenic mice model

Amyotrophic lateral sclerosis is a progressive, fatal neurode-generative disease characterized by damage of the motor neurons of the brain and spinal cord. The lack of effective methods of therapy of amyotrophic lateral sclerosis is one of the most important problems of contemporary medicine. The aim of this work was to study the effectiveness of combined use of the antioxidant drug edaravone and gene-cell therapy with umbilical cord blood mononuclear cells producing vascular endothelial growth factor, glial cell-derived neurotrophic factor and neural cell adhesion molecule in the model of amyotrophic lateral sclerosis on mSOD1 transgenic mice. Analysis of survival dynamics of mSOD1 transgenic mice showed that gene-cell therapy is more effective than edaravone therapy or combined therapy. Conducting of behavioral tests showed that all types of used therapy are able to support the parameters of horizontal activity and grip strength test of mSOD1 mice during 8 weeks from beginning of the therapy at the level corresponding to wild type mice. Conducted study showed that gene-cell therapy with use of umbilical cord blood mononuclear cells producing vascular endothelial growth factor, glial cell-derived neurotrophic factor and neural cell adhesion molecule is more effective than antioxidant therapy with edaravone or combined (antioxidant and gene-cell) therapy. These findings could be used in studies aimed on development of treatment of amyotrophic lateral sclerosis.

Reduction in Migraine and Headache Frequency and Intensity With Combined Antioxidant Prophylaxis (N-acetylcysteine, Vitamin E, and Vitamin C): A Randomized Sham-Controlled Pilot Study.

To investigate the preventive effects of a combined antioxidant drug (N-acetylcysteine, vitamin E, and vitamin C [NEC]) on migraine outcomes. Migraine is characterized by increased oxidative stress and neurogenic inflammation in the brain; therefore, antioxidants may have a migraine preventive effect. Randomized, double-blind, sham-controlled pilot study. Australian community. Adults reporting 2 to 8 migraines per month for at least a year. After a 1-month baseline period, 35 subjects completed 3months of treatment with NEC (n=19) or sham (n=16) capsules. The primary outcome was the difference in mean number of headaches per month between baseline and final month of the trial for NEC and sham groups; secondary outcomes are listed below. For NEC there was a significant decrease in mean number of headaches by 3.0 per month (P=0.004) compared with 1.4 for sham (P=0.073); there was no significant difference in these changes between the 2 groups (P=0.052). Average monthly headache (P=0.041) and migraine frequency (P=0.018) were significantly less for NEC vs. sham. In NEC subjects, there was a significant decrease in average monthly migraine days (-3.1), moderate/severe headache days (-3.2), migraine duration, headache pain scores, and acute headache medication use. This is the first randomized controlled trial to find that combined antioxidant therapy with NEC reduces headaches and migraines in adult migraineurs. Given the limitations of this pilot study, an adequately powered randomized controlled trial is planned to further investigate antioxidant prophylaxis in migraine.

Combination therapy with antioxidants improves total motile sperm counts: A Preliminary Study.

PurposeOptimal strategies to treat idiopathic male infertility have remained unclear. The aim of this study was to evaluate the effectiveness of combination antioxidant therapy with several vitamins and supplements on semen parameters.MethodsThirty‐one men with oligozoospermia and/or asthenozoospermia evaluated by a Makler counting chamber were randomly assigned to two treatment groups: a combination of antioxidant supplements (L‐carnitine, zinc, astaxanthin, coenzyme Q10, vitamin C, vitamin B12, and vitamin E) and a Chinese herbal medicine, hochu‐ekki‐to (HE). Serum endocrinological profiles and semen parameters, especially total motile sperm count, were compared between before and after 12 weeks of treatment in both groups.ResultsIn the supplement group, endocrinological findings were not significantly improved. The semen parameters of semen volume, sperm concentration, and sperm motility were not statistically significantly improved, whereas total motile sperm count was significantly improved. In contrast, none of the endocrinological factors or semen findings were significantly improved by the Chinese herbal medicine although semen concentration, semen motility, and total motile sperm count showed a tendency to increase.ConclusionBecause combination antioxidant therapy could improve sperm motility significantly for patients with idiopathic oligoasthenozoospermia, our supplement could be one treatment option for idiopathic male infertility.

Comparative study on some oxidative stress parameters in blood of vitiligo patients before and after combined therapy

Currently accepted that oxidative stress is a triggering event in the melanocytic destruction and is probably involved in the etiopathogenesis of vitiligo disease. Despite numerous investigations, contradictory results were reported about the levels of oxidative stress biomarkers measured in the skin and blood of vitiligo patients. By Electron Paramagnetic Resonance spectroscopy (EPR) and spectrophotometry, we have investigated and compared some oxidative stress biomarkers in the blood of vitiligo patients' before and after UVB Narrow Band 311 nm phototherapy combined with the antioxidant nutritional supplement containing - Vitamin C, Vitamin B1, L -Cysteine, Lipoic Acid, and polyunsaturated fatty acids.Before therapy was found significantly higher levels of CAT activity and MDA compared to the patients after therapy and control group (p < 0.05). Moreover, levels of Asc* radicals in patients before therapy were significantly lower than those measured in controls and patients undergoing therapy (p < 0.05). Our finding, the combined therapy applied to vitiligo patients provoked an increase in the Asc* levels and a decrease in MDA products and also initial repigmentation in the vitiligo spots, made us believe that a combined antioxidant therapy, enriched with vitamin C could lead to improvement of the oxidant-antioxidant balance in vitiligo patients treated with UVB 311 phototherapy.

A combination antioxidant therapy to inhibit NOX2 and activate Nrf2 decreases secondary brain damage and improves functional recovery after traumatic brain injury

Uncontrolled oxidative stress contributes to the secondary neuronal death that promotes long-term neurological dysfunction following traumatic brain injury (TBI). Surprisingly, both NADPH oxidase 2 (NOX2) that increases and transcription factor Nrf2 that decreases reactive oxygen species (ROS) are induced after TBI. As the post-injury functional outcome depends on the balance of these opposing molecular pathways, we evaluated the effect of TBI on the motor and cognitive deficits and cortical contusion volume in NOX2 and Nrf2 knockout mice. Genetic deletion of NOX2 improved, while Nrf2 worsened the post-TBI motor function recovery and lesion volume indicating that decreasing ROS levels might be beneficial after TBI. Treatment with either apocynin (NOX2 inhibitor) or TBHQ (Nrf2 activator) alone significantly improved the motor function after TBI, but had no effect on the lesion volume, compared to vehicle control. Whereas, the combo therapy (apocynin + TBHQ) given at either 5 min/24 h or 2 h/24 h improved motor and cognitive function and decreased cortical contusion volume compared to vehicle group. Thus, both the generation and disposal of ROS are important modulators of oxidative stress, and a combo therapy that prevents ROS formation and potentiates ROS disposal concurrently is efficacious after TBI.

Rationale of combination therapy with antioxidants in medical management of Peyronie&amp;rsquo;s disease: results of clinical application

Peyronie’s disease (PD) is a connective tissue disorder involving the tunica albuginea of the corpora cavernosa of the penis. We have published several studies describing a “combined therapy” for PD patients, but the present study aims to clearly demonstrate how the association between various antioxidants in PD treatment can significantly increase the likelihood of therapeutic success. We used the following substances: silymarin, ginkgo biloba, vitamin E, bilberry, topical diclofenac sodium, and pentoxifylline (PTX). We analyzed the therapeutic impact and possible side effects of one or more antioxidants in patients with early-stage PD. To clearly prove that it is possible to achieve better results when combining more than one agent, we designed this study with five treatment groups, corresponding, respectively, to the administration of a single oral antioxidant; two oral antioxidants; three oral antioxidants; five oral antioxidants + local diclofenac; and five oral antioxidants + local diclofenac + PTX by perilesional injection. One hundred and twenty patients were assigned to five groups of treatment designed according to the abovementioned study aim. Outcomes after 6 months of treatment showed that combined antioxidant therapy is effective in treating PD. Statistical analysis showed significant differences between the treatment groups with regard to: improvement and disappearance of penile pain; percentage of reduction in the volume of penile plaque; reduction in penile curvature; recovery of erectile function in patients with erectile dysfunction; increase in the International Index of Erectile Function score; and reduction of psychosexual impact. Furthermore, we observed that the clinical efficacy of combined therapy is greater when topical use of diclofenac gel and perilesional injection of PTX are added to oral treatment with more than one antioxidant. Although several articles have already been published reporting the effectiveness of combined treatment in PD, this is the first study clearly proving how, as the number of substances used in treatment rises, a proportionally greater therapeutic effect is achieved.

Free radical scavenging injectable hydrogels for regenerative therapy

Pathological free radicals generated from inflamed and infarcted cardiac tissues interferes natural tissue repair mechanisms. Hypoxic microenvironment at the injured zone of non-regenerating cardiac tissues hinders the therapeutic attempts including cell therapy. Here we report an injectable, cytocompatible, free radical scavenging synthetic hydrogel formulation for regenerative therapy. New hydrogel (PEAX-P) is prepared with D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer (PEAX) and PEGDiacrylate. PEAX-P hydrogel swells 4.9 times the initial weight and retains 100.07kPa Young modulus at equilibrium swelling, which is suitable for cardiac applications. PEAX-P hydrogel retains elastic nature even at 60% compressive strain, which is favorable to fit with the dynamic and elastic natural tissue counterparts. PEAX-P hydrogel scavenges 51% DPPH radical, 40% hydroxyl radicals 41% nitrate radicals with 31% reducing power. The presence of hydrogel protects 62% cardiomyoblast cells treated with stress inducing media at LD 50 concentration. The free hydroxyl groups in sugar alcohols of the comacromer influence the free radical scavenging. Comparatively, PEAX-P hydrogel based on xylitol evinces slightly lower scavenging characteristics than with previously reported PEAM-P hydrogel containing mannitol having more hydroxyl groups. The possible free radical scavenging mechanism of the present hydrogel relies on the free π electrons associated with uncrosslinked fumarate bonds, hydrogen atoms associated with sugar alcohols/PEG and radical dilution by free water in the matrix. Briefly, the present PEAX-P hydrogel is a potential injectable system for combined antioxidant and regenerative therapy.