Development and Evaluation of Virola oleifera Formulation for Cutaneous Wound Healing.

In regions adjacent to the Brazilian Atlantic Forest, Virola oleifera (VO) resin extract has been popularly used for decades as a skin and mucosal healing agent. However, this antioxidant-rich resin has not yet been investigated in wound healing, whose physiological process might also be aggravated by oxidative stress-related diseases (e.g., hypertension/diabetes). Our aim, therefore, was to investigate whether VO resin presents healing effects through an innovative cream for topical applications. For this, adult male Wistar rats were divided into four groups. Then, four 15 mm excisions were performed on the shaved skin. All treatments were applied topically to the wound area daily. At the end of experiments (0, 3rd, and 10th days) macroscopic analysis of wound tissue contraction and histological analysis of inflammatory cell parameters were performed. The group treated with VO cream showed the best wound contraction (15%, p < 0.05) and reduced levels of lipid peroxidation and protein oxidation (118% and 110%, p < 0.05, respectively) compared to the control group. Our results demonstrated the healing capacity of a new formulation prepared with VO, which could be, at least in part, justified by antioxidant mechanisms that contribute to re-epithelialization, becoming a promising dermo-cosmetic for the treatment of wound healing.

DNA damage and repair on hematopoietic stem cells: impact of oxidative stress in renovascular hypertension.

BACKGROUND: This study investigated oxidative damage to bone marrow cells in the pathogenesis of renovascular hypertension (RH). METHODS: Male C57BL/6 J mice (10-week-old and ~23 g) were divided into two groups: Sham-operated and 2K1C, which has a stainless-steel clip placed around the left renal artery. After twenty-eight days, the animals were anesthetized for hemodynamic measurements and bone marrow cells isolation. The intracellular production of ROS, DNA damage, and DNA repair kinetics were evaluated. RESULTS: Our results show that RH increases HSCs ROS production and that the 2K1C group showed a significant reduction of HSCs in the G0/G1 phase, increased p53 expression, DNA fragmentation, low DNA repair capacity, and a higher percentage of apoptotic cells when compared with the Sham group. CONCLUSIONS: Our data imply that RH can compromise the hematopoiesis by increased oxidative stress leading to impaired DNA repair activity. Furthermore, this study provides new insights into the influence of hypertension on bone marrow homeostasis. This study showed for the first time that RH leads to oxidative damage, including genotoxic, to bone marrow cells. Thus, these findings provide new insights into the consequences of RH on bone marrow cells.

The Gut Microbiota-Brain Axis: A New Frontier on Neuropsychiatric Disorders.

Alzheimer's disease (AD) is a progressive and incurable neurodegenerative disorder of integrative areas of the brain, characterized by cognitive decline and disability resulting in negative impacts on the family of the patients and the health care services worldwide. AD involves oxidative stress, neuroinflammation and accelerated apoptosis, accompanied by deposition of amyloid-ß peptide plaques and tau protein-based neurofibrillary tangles in the central nervous system. Among the multiple factors that contribute to the onset and evolution of this disease, aging stands out. That is why the prevalence of this disease has increased due to the constant increase in life expectancy. In the hope of finding new, more effective methods to slow the progression of this disease, over the last two decades, researchers have promoted "omics"-based approaches that include the gut microbiota and their reciprocal interactions with different targets in the body. This scientific advance has also led to a better understanding of brain compartments and the mechanisms that affect the integrity of the blood-brain barrier. This review aims to discuss recent advances related to the gut-brain-microbiota axis in AD. Furthermore, considering that AD involves psychiatric symptoms, this review also focuses on the psychiatric factors that interact with this axis (an issue that has not yet been sufficiently addressed in the literature).

Optimal Parameters of Laser Therapy to Improve Critical Calvarial Defects.

Body bones play diverse pivotal roles, including the protection of vital organs. For instance, the integrative functions of the brain controlling diverse peripheral actions can be affected by a traumatic injury on the calvaria and the reparative process of a large defect is a challenge in the integrative physiology. Therefore, the development of biomaterials and approaches to improve such defects still requires substantial advances. In this regard, the most attractive approaches have been covering the cavity with inorganic bovine bone (IBB) and, more recently, also using low-level laser therapy (LT), but this issue has opened many questions. Here, it was determined the number of LT sessions required to speed up and to intensify the recovery process of two 5-mm-diameter defects promoted in the calvaria of each subgroup of six adult Wistar rats. The quantitative data showed that 30 days post-surgery, the recovery process by using blood clot-filling was not significantly influenced by the number of LT sessions. However, in the IBB-filled defects, the number of LT sessions markedly contributed to the improvement of the reparative process. Compared to the Control group (non-irradiated), the percentage of mineralization (formation of new bone into the cavities) gradually increased 25, 49, and 52% with, respectively, 4, 7, and 11 sessions of LT. In summary, combining the use of IBB with seven sessions of LT seems to be an optimal approach to greatly improve the recovery of calvarial defects. This translational research opens new avenues targeting better conditions of life for those suffering from large bone traumas and in the present field could contribute to preserve the integrative functions of the brain.

Benefits of multi-day supplementation with probiotic kefir in Rasmussen encephalitis: the first case report.

INTRODUCTION: Rasmussen encephalitis (RE) is a rare inflammatory disease, characterized by unilateral hemispheric atrophy, focal intractable seizures, progressive hemiparesis, and neurological deficits. CASE REPORT: The patient is a young man under pharmacotherapy for epilepsy, exhibiting classical abnormal movements, which are consider typical hallmarks of RE. During clinical care sessions, he presented many episodes of tonic-clonic seizures involving sudden loss of consciousness followed by a post-ictal phase with weakness and interaction difficulty. During the kefir supplementation, the patient presented only short-term absence seizures, quickly returning to activities. Additionally, he presented cognitive and language improvement, being more responsive to commands. The daily diary control of patient's mother and caregiver at school reported an impressive reduction in number and severity of seizures, becoming less aggressive and more involved in school activities. The serum biochemical markers showed that kefir administration caused a significant decrease of pro-inflammatory and a simultaneous increase of anti-inflammatory cytokine levels. In parallel, after treatment, this probiotic reduced reactive oxygen species levels, increased NO bioavailability, revealing antiapoptotic and antigenotoxic effects. Regarding the microbiological analysis, kefir increased Lactobacillus and Bifidobacterium species. CONCLUSION: To our knowledge, this is the first case reporting remarkable beneficial effects of the probiotic kefir in RE. This case report strongly suggests kefir supplementation as a potential and safe-effective adjuvant therapeutic strategy in the control and treatment of RE.

The Emerging Scenario of the Gut-Brain Axis: The Therapeutic Actions of the New Actor Kefir against Neurodegenerative Diseases.

The fact that millions of people worldwide suffer from Alzheimer's disease (AD) or Parkinson's disease (PD), the two most prevalent neurodegenerative diseases (NDs), has been a permanent challenge to science. New tools were developed over the past two decades and were immediately incorporated into routines in many laboratories, but the most valuable scientific contribution was the "waking up" of the gut microbiota. Disturbances in the gut microbiota, such as an imbalance in the beneficial/pathogenic effects and a decrease in diversity, can result in the passage of undesired chemicals and cells to the systemic circulation. Recently, the potential effect of probiotics on restoring/preserving the microbiota was also evaluated regarding important metabolite and vitamin production, pathogen exclusion, immune system maturation, and intestinal mucosal barrier integrity. Therefore, the focus of the present review is to discuss the available data and conclude what has been accomplished over the past two decades. This perspective fosters program development of the next steps that are necessary to obtain confirmation through clinical trials on the magnitude of the effects of kefir in large samples.

cAMP Compartmentalization in Cerebrovascular Endothelial Cells: New Therapeutic Opportunities in Alzheimer's Disease.

The vascular hypothesis used to explain the pathophysiology of Alzheimer's disease (AD) suggests that a dysfunction of the cerebral microvasculature could be the beginning of alterations that ultimately leads to neuronal damage, and an abnormal increase of the blood-brain barrier (BBB) permeability plays a prominent role in this process. It is generally accepted that, in physiological conditions, cyclic AMP (cAMP) plays a key role in maintaining BBB permeability by regulating the formation of tight junctions between endothelial cells of the brain microvasculature. It is also known that intracellular cAMP signaling is highly compartmentalized into small nanodomains and localized cAMP changes are sufficient at modifying the permeability of the endothelial barrier. This spatial and temporal distribution is maintained by the enzymes involved in cAMP synthesis and degradation, by the location of its effectors, and by the existence of anchor proteins, as well as by buffers or different cytoplasm viscosities and intracellular structures limiting its diffusion. This review compiles current knowledge on the influence of cAMP compartmentalization on the endothelial barrier and, more specifically, on the BBB, laying the foundation for a new therapeutic approach in the treatment of AD.

Subchronic and Low Dose of Tributyltin Exposure Leads to Reduced Ovarian Reserve, Reduced Uterine Gland Number, and Other Reproductive Irregularities in Female Mice.

Tributyltin (TBT) chloride is an endocrine disrupting chemical associated with reproductive complications. Studies have shown that TBT targets the reproductive tract, impairing ovarian folliculogenesis, and uterine morphophysiology. In this investigation, we assessed whether subchronic and low dose of TBT exposure results in abnormal ovarian follicular reserve and other irregularities in female mice. TBT was administered to female mice (500 ng/kg/day for 12 days via gavage), and reproductive tract morphophysiology was assessed. We further assessed reproductive tract inflammation and oxidative stress. Improper functioning of the reproductive tract in TBT mice was observed. Specifically, irregular estrous cyclicity and abnormal ovarian morphology coupled with reduction in primordial and primary follicle numbers was observed, suggesting ovarian reserve depletion. In addition, improper follicular development and a reduction in antral follicles, corpora lutea, and total healthy ovarian follicles together with an increase in cystic follicles were apparent. Evidence of uterine atrophy, reduction in endometrial gland number, and inflammation and oxidative stress were seen in TBT mice. Further, strong negative correlations were observed between testosterone levels and primordial, primary, and total healthy ovarian follicles. Thus, these data suggest that the subchronic and low dose of TBT exposure impaired ovarian follicular reserve, uterine gland number, and other reproductive features in female mice.

New Insights on the Beneficial Effects of the Probiotic Kefir on Vascular Dysfunction in Cardiovascular and Neurodegenerative Diseases.

The mechanisms responsible for cardiovascular and neurodegenerative diseases have been the focus of experimental and clinical studies for decades. The relationship between the gut microbiota and the organs and system tissues represents the research field that has generated the highest number of publications. Homeostasis of the gut microbiota is important to the host because it promotes maturation of the autoimmune system, harmonic integrative functions of the brain, and the normal function of organs related to cardiovascular and metabolic systems. On the other hand, when a gut microbiota dysbiosis occurs, the target organs become vulnerable to the onset or aggravation of complex chronic conditions, such as cardiovascular (e.g., arterial hypertension) and neurodegenerative (e.g., dementia) diseases. In the present brief review, we discuss the main mechanisms involved in those disturbances and the promising beneficial effects that have been revealed using functional food (nutraceuticals), such as the traditional probiotic Kefir. Here, we highlight the current scientific advances, concerns, and limitations about the use of this nutraceutical. The focus of our discussion is the endothelial dysfunction that accompanies hypertension and the neurovascular dysfunction that characterizes ageing-related dementia in patients suffering from Alzheimer's disease.

Sildenafil reduces aortic endothelial dysfunction and structural damage in spontaneously hypertensive rats: Role of NO, NADPH and COX-1 pathways.

Arterial hypertension is a condition associated with endothelial dysfunction, accompanied by an imbalance in the production of reactive oxygen species (ROS) and NO. The aim of this study was to investigate and elucidate the possible mechanisms of sildenafil, a selective phosphodiesterase-5 inhibitor, actions on endothelial function in aortas from spontaneously hypertensive rats (SHR). SHR treated with sildenafil (40 mg/kg/day, p.o., 3 weeks) were compared to untreated SHR and Wistar-Kyoto (WKY) rats. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography and vascular reactivity was determined in isolated rat aortic rings. Circulating endothelial progenitor cells and systemic ROS were measured by flow cytometry. Plasmatic total antioxidant capacity, NO production and aorta lipid peroxidation were determined by spectrophotometry. Scanning electron microscopy was used for structural analysis of the endothelial surface. Sildenafil reduced high SBP and partially restored the vasodilator response to acetylcholine and sodium nitroprusside in SHR aortic rings. Using selective inhibitors, our experiments revealed an augmented participation of NO, with a simultaneous decrease of oxidative stress and of cyclooxygenase-1 (COX-1)-derived prostanoids contribution in the endothelium-dependent vasodilation in sildenafil-treated SHR compared to non-treated SHR. Also, the relaxant responses to sildenafil and 8-Br-cGMP were normalized in sildenafil-treated SHR and sildenafil restored the pro-oxidant/antioxidant balance and the endothelial architecture. In conclusion, sildenafil reverses endothelial dysfunction in SHR by improving vascular relaxation to acetylcholine with increased NO bioavailability, reducing the oxidative stress and COX-1 prostanoids, and improving cGMP/PKG signaling. Also, sildenafil reduces structural endothelial damage. Thus, sildenafil is a promising novel pharmacologic strategy to treat endothelial dysfunction in hypertensive states reinforcing its potential role as adjuvant in the pharmacotherapy of cardiovascular diseases.

Bisphenol A contamination in infant rats: molecular, structural, and physiological cardiovascular changes and the protective role of kefir.

The effects of bisphenol A (BPA) contamination on the cardiovascular function still are not clear. Here, we evaluated the vascular effects of BPA and the protective actions of kefir in infant rats. Animals (25 days old) were treated with BPA (100 µg/Kg/day) for 60 days (BPA group), or administered kefir (0.3 mL/100 g) in addition to BPA (BPA kefir group), compared with non-treated rats (Control group).The vascular endothelial function was evaluated in aortic rings through the relaxation response to acetylcholine and specific blockers. The balance between reactive oxygen species (ROS) and nitric oxide (NO) was assessed through flow cytometry in the vascular tissue. The BPA group developed high blood pressure (+10%) and the analysis of vascular reactivity showed an impaired ACh-induced relaxation (~80%). The further analysis by using NADPH, NOS and COX blockers revealed that the impaired vasorelaxation was due to increased ROS production (+12%), NO bioavailability (-12%) and increased vasoconstriction to prostanoids (+36%) compared with the Control group. Kefir treatment reverted those effects significantly. Analysis of the aortic cells showed increased •O2- production (1942±39 a.u.) and decreased NO bioavailability (1250±30 a.u.) compared with the Control group (1374±146 and 2777±25 a.u., P<.05) and kefir reverted these values (1298±57 and 2517±57 a.u.). Contamination by BPA in this model caused hypertension and endothelial dysfunction and it was accompanied by a vascular ROS/NO imbalance, damage of endothelial layer and pro-apoptotic effects. The novelty is that the treatment using probiotic kefir was able to attenuate the progression the above BPA effects.

Probiotics as Beneficial Dietary Supplements to Prevent and Treat Cardiovascular Diseases: Uncovering Their Impact on Oxidative Stress.

The gut microbiota, the ecosystem formed by a wide symbiotic community of nonpathogenic microorganisms that are present in the distal part of the human gut, plays a prominent role in the normal physiology of the organism. The gut microbiota's imbalance, gut dysbiosis, is directly related to the origin of various processes of acute or chronic dysfunction in the host. Therefore, the ability to intervene in the gut microbiota is now emerging as a possible tactic for therapeutic intervention in various diseases. From this perspective, evidence is growing that a functional dietary intervention with probiotics, which maintain or restore beneficial bacteria of the digestive tract, represents a promising therapeutic strategy for interventions in cardiovascular diseases and also reduces the risk of their occurrence. In the present work, we review the importance of maintaining the balance of the intestinal microbiota to prevent or combat such processes as arterial hypertension or endothelial dysfunction, which underlie many cardiovascular disorders. We also review how the consumption of probiotics can improve autonomic control of cardiovascular function and provide beneficial effects in patients with heart failure. Among the known effects of probiotics is their ability to decrease the generation of reactive oxygen species and, therefore, reduce oxidative stress. Therefore, in this review, we specifically focus on this antioxidant capacity and its relationship with the beneficial cardiovascular effects described for probiotics.

Antioxidant effect of sildenafil: Potential hepatoprotection via differential expression of mitochondrial proteins in apolipoprotein E knockout mice.

BACKGROUND: High plasma cholesterol levels are able to trigger several pathophysiological events, including inflammation, cell damage and especially oxidative stress. Previously, studies have shown that sildenafil exhibited antioxidant effects in several experimental models. Here we evaluate the role of sildenafil in liver redox equilibrium of apolipoprotein E knockout (apoE-KO) mice. METHODS: ApoE-KO mice were divided in two groups: one group received the PDE5 inhibitor sildenafil (40 mg/kg/day) for 3 weeks (apoE-KO + Sil) and was compared to a second group of apoE-KO mice, which received only the vehicle (water) for 3 weeks (apoE-KO). Control group (C57 mice) received only a standard chow diet. At the age of 18 weeks, mice livers were collected for the measurement of intracellular ROS levels and apoptotic cells by flow cytometry analysis, and mitochondria isolation for proteomic analysis. RESULTS: Compared to the control group, liver cells from apoE-KO presented some typical redox imbalance features: higher levels of intracellular ROS (global oxidative stress ˜60%, superoxide anion ˜82%, and peroxynitrite/hydroxyl radical ˜53%), higher amounts of apoptotic cells (up to ˜19%) and higher mitochondrial intensity of catalase (+339%) and transferrin spots (+914%). After treatment with sildenafil, apoE-KO presented ROS levels and the number of apoptotic cells similar to those observed in C57. In addition, when compared to apoE-KO, apoE-KO + Sil showed lower spots volumes of catalase (-23%) and transferrin (-71%) and up-regulation of urate oxidase (+94%). CONCLUSION: The treatment with sildenafil is able to induce beneficial changes in liver mitochondrial protein dynamics, which restores the redox homeostasis contributing to a potential hepatoprotection.

Increased ROS production and DNA damage in monocytes are biomarkers of aging and atherosclerosis.

BACKGROUND: New evidence demonstrates that aging and dyslipidemia are closely associated with oxidative stress, DNA damage and apoptosis in some cells and extravascular tissues. However, in monocytes, which are naturally involved in progression and/or resolution of plaque in atherosclerosis, this concurrence has not yet been fully investigated. In this study, we evaluated the influence of aging and hypercholesterolemia on serum pro-inflammatory cytokines, oxidative stress, DNA damage and apoptosis in monocytes from apolipoprotein E-deficient (apoE-/-) mice compared with age-matched wild-type C57BL/6 (WT) mice. Experiments were performed in young (2-months) and in old (18-months) male wild-type (WT) and apoE-/- mice. RESULTS: Besides the expected differences in serum lipid profile and plaque formation, we observed that atherosclerotic mice exhibited a significant increase in monocytosis and in serum levels of pro-inflammatory cytokines compared to WT mice. Moreover, it was observed that the overproduction of ROS, led to an increased DNA fragmentation and, consequently, apoptosis in monocytes from normocholesterolemic old mice, which was aggravated in age-matched atherosclerotic mice. CONCLUSIONS: In this study, we demonstrate that a pro-inflammatory systemic status is associated with an impairment of functionality of monocytes during aging and that these parameters are fundamental extra-arterial contributors to the aggravation of atherosclerosis. The present data open new avenues for the development of future strategies with the purpose of treating atherosclerosis.

Mechanisms of Action of Kefir in Chronic Cardiovascular and Metabolic Diseases.

The gut microbiota maintains a complex mutual interaction with different organs of the host. Whereas in normal conditions this natural community of trillions of microorganisms greatly contributes to the human health, gut dysbiosis is related with onset or worsening of diverse chronic systemic diseases. Thus, the reestablishment of gut microbiota homeostasis with consumption of prebiotics and probiotics may be a relevant strategy to prevent or attenuate several cardiovascular and metabolic complications. Among these functional foods, the synbiotic kefir, which is a fermented milk composed of a mixture of bacteria and yeasts, is currently the most used and has attracted the attention of health care professionals. The present review is focused on reports describing the feasibility of kefir consumption to provide benefits in cardiometabolic diseases, including hypertension, vascular endothelial dysfunction, dyslipidemia and insulin resistance. Interestingly, recent studies show that mechanisms of actions of kefir in cardiometabolic diseases include recruitment of endothelial progenitor cells, improvement of the balance vagal/sympathetic nervous system, diminution of excessive generation of reactive oxygen species, angiotensin converting enzyme inhibition, anti-inflammatory cytokines profile and alteration of the intestinal microbiota. These findings provide a better understanding about the mechanisms of the beneficial actions of kefir and motivate further investigations to determine whether the use of this synbiotic could also be translated into clinical improvements in cardiometabolic diseases.

Low Doses of G-CSF Prevent Cerebral Infarction and Maintain Muscle Strength in an Experimental Model of Global Ischemic Stroke.

BACKGROUND: Stroke is a major cause of severe and long-term disability in adult individuals. Treatment of this disease is limited by the narrow therapeutic window in which intervention is crucial. An alternative therapy for stroke could be cellular growth factors, which participate in several pathways that mediate neuronal cell death. METHODS: We evaluated the neuroprotective ability of different doses of granulocyte colonystimulating factor (G-CSF; 5, 50 and 100 µg/kg/day) in the mouse model of global cerebral ischemia induced by bilateral occlusion of the common carotid arteries for 80 minutes. The control group received vehicle (5% glucose solution) and the treated group was administered with G-CSF at two postsurgery time-points: immediately after and 24 hours after. Subsequently, muscle strength, leukocyte count, infarcted cortical area, and apoptosis/TUNEL were evaluated. RESULTS: The global ischemia promoted an impairment of the strength (16%) and a cerebral infarction (0.437±0.08 cm2) which were accompanied by apoptosis evaluated by TUNEL in control mice. In mice treated with G-CSF the strength function was maintained, the infarcted area (~70%) and apoptosis were decreased in a similar magnitude in all treated groups. Accordingly, the cytokine activities were confirmed by blood leukocyte count that was increased approximately 2-fold than that observed in the control group. CONCLUSION: The results indicate a neuroprotective effect of G-CSF, even in small doses, in mice subjected to global cerebral ischemia, thereby reducing the neurofunctional impairment caused by stroke, when considering the maintenance of muscle strength in the treated animals.

Beneficial Morphofunctional Changes Promoted by Sildenafil in Resistance Vessels in the Angiotensin II-Induced Hypertension Model.

BACKGROUND: By acting on multiple targets and promoting diverse actions, angiotensin II (Ang II) plays a pivotal role in vascular function. Recent studies suggested that phosphodiesterase-5 (PDE-5) inhibitors exhibit therapeutic effects in cardiovascular diseases. Here, the effects of sildenafil on vascular disturbances were analyzed in a mouse model of Ang II-induced hypertension. METHODS AND RESULTS: Male C57BL/6 mice were used as untreated animals (control) or infused with Ang II (1000 ηg/kg/min) for 28 days and treated with sildenafil (40 mg/kg/min) or vehicle (Ang II) during the last two weeks. After 4 weeks, the Ang II animals exhibited a high systolic blood pressure (186±3 mmHg vs. 127±3 mmHg for control mice), which was attenuated by sildenafil (163±7 mmHg). The mesenteric vessels from the Ang II animals revealed damage to the endothelial layer, an increase in the cross-section area (1.9-fold) and vascular cell production of peroxynitrite (512±13 a.u.), which was ameliorated in the Ang II-Sil group (1.2-fold and 400±17 a.u.). Analysis of the vascular responsiveness showed an increased contractility response to norepinephrine in Ang II animals (Rmax: 70%), which was abolished by sildenafil through increased nitric oxide (NO) bioavailability and decreased reactive oxygen species (ROS) and vasoconstrictor prostanoids. CONCLUSION: Sildenafil attenuates the morphofunctional deleterious effects of Ang II on resistance vessels. The benefits of sildenafil seem to occur through restoring the balance of ROS/NO/eicosanoids. Therefore, this study opened new avenues for further clinical targeting of the treatment of cardiovascular diseases related to activation of the renin-angiotensin system.

Blood flow restriction attenuates eccentric exercise-induced muscle damage without perceptual and cardiovascular overload.

The aim of this study was to evaluate the acute effects of high-intensity eccentric exercise (HI-ECC) combined with blood flow restriction (BFR) on muscle damage markers, and perceptual and cardiovascular responses. Nine healthy men (26 ± 1 years, BMI 24 ± 1 kg m- ²) underwent unilateral elbow extension in two conditions: without (HI-ECC) and with BFR (HI-ECC+BFR). The HI-ECC protocol corresponded to three sets of 10 repetitions with 130% of maximal strength (1RM). The ratings of perceived exertion (RPE) and pain (RPP) were measured after each set. Muscle damage was evaluated by range of motion (ROM), upper arm circumference (CIR) and muscle soreness using a visual analogue scale at different moments (pre-exercise, immediately after, 24 and 48 h postexercise). Systolic (SBP), diastolic (DBP), mean blood pressure (MBP) and heart rate (HR) were measured before exercise and after each set. RPP was higher in HI-ECC+BFR than in HI-ECC after each set. Range of motion decreased postexercise in both conditions; however, in HI-ECC+BFR group, it returned to pre-exercise condition earlier (post-24 h) than HI-ECC (post-48 h). CIR increased only in HI-ECC, while no difference was observed in HI-ECC+BFR condition. Regarding cardiovascular responses, MBP and SBP did not change at any moment. HR showed similar increases in both conditions during exercise while DBP decreased only in HI-ECC condition. Thus, BFR attenuated HI-ECC-induced muscle damage and there was no increase in cardiovascular responses.

Increased ROS production and DNA damage in monocytes are biomarkers of aging and atherosclerosis

BACKGROUND: New evidence demonstrates that aging and dyslipidemia are closely associated with oxidative stress, DNA damage and apoptosis in some cells and extravascular tissues. However, in monocytes, which are naturally involved in progression and/or resolution of plaque in atherosclerosis, this concurrence has not yet been fully investigated. In this study, we evaluated the influence of aging and hypercholesterolemia on serum pro-inflammatory cytokines, oxidative stress, DNA damage and apoptosis in monocytes from apolipoprotein E-deficient (apoE-/-) mice compared with age-matched wild-type C57BL/6 (WT) mice. Experiments were performed in young (2-months) and in old (18-months) male wild-type (WT) and apoE-/- mice. RESULTS: Besides the expected differences in serum lipid profile and plaque formation, we observed that atherosclerotic mice exhibited a significant increase in monocytosis and in serum levels of pro-inflammatory cytokines compared to WT mice. Moreover, it was observed that the overproduction of ROS, led to an increased DNA fragmentation and, consequently, apoptosis in monocytes from normocholesterolemic old mice, which was aggravated in age-matched atherosclerotic mice. CONCLUSIONS: In this study, we demonstrate that a pro-inflammatory systemic status is associated with an impairment of functionality of monocytes during aging and that these parameters are fundamental extra-arterial contributors to the aggravation of atherosclerosis. The present data open new avenues for the development of future strategies with the purpose of treating atherosclerosis.