Polystyrene nanoplastics induce developmental impairments and vasotoxicity in zebrafish (Danio rerio).

The exponential use of plastics has significantly increased environmental pollution by nanoplastics (NPs). In the aquatic environment, NPs interact and bioaccumulate in the biota, posing a potential ecotoxicological risk. The present study investigated the developmental toxicity, vasotoxicity, cytotoxicity, ROS induction, and behavioral impairments in zebrafish (Danio rerio) exposed to environmentally relevant polystyrene NPs (PS-NPs) concentrations (0.04, 34 ng L-1, and 34 µg L-1) for 144 h through multiple biomarkers response (mortality, frequency of spontaneous contractions, heart rate, and morphological changes). Furthermore, vasotoxicity (head, yolk sac, tail, and branchial vessels) was evaluated using the transgenic zebrafish tg(Fli1:eGFP). Results showed that PS-NPs interacted mainly with zebrafish chorion, gills, tail, and larvae head. PS-NPs at 34 ng L-1 and 34 µg L-1 induced neurotoxicity (decreased frequency of spontaneous contractions), cardiotoxicity (bradycardia), and morphological changes in the eyes and head, indicating that PS-NPs induce developmental impairments in zebrafish. In addition, cytotoxicity in the caudal region (34 ng L-1), ROS production, decreased mean swimming speed, and distance covered were observed in all tested concentrations. PS-NPs also induced vasotoxicity (yolk sac region) in transgenic zebrafish. Overall, the present study demonstrates the harmful effects of PS-NPs on the early developmental stages of freshwater fish, indicating their environmental risk.

Melatonin prevents overproduction of reactive oxygen species and vascular dysfunction induced by cyclophosphamide.

AIMS: Overproduction of reactive oxygen species (ROS) is a pathologic hallmark of cyclophosphamide toxicity. For this reason, antioxidant compounds emerge as promising tools for preventing tissue damage induced by cyclophosphamide. We hypothesized that melatonin would display cytoprotective action in the vasculature by preventing cyclophosphamide-induced oxidative stress. MATERIALS AND METHODS: Male C57BL/6 mice (22-25 g) were injected with a single dose of cyclophosphamide (300 mg/kg; i.p.). Mice were pretreated or not with melatonin (10 mg/kg/day, i.p.), given during 4 days before cyclophosphamide injection. Functional (vascular reactivity) and oxidative/inflammatory patterns were evaluated at 24 h in resistance arteries. The antioxidant action of melatonin was assessed in vitro in cultured vascular smooth muscle cells (VSMCs) of mesenteric arteries. KEY FINDINGS: Cyclophosphamide induced ROS generation in both mesenteric arterial bed (MAB) and cultured VSMCs, and this was normalized by melatonin. Cyclophosphamide-induced ROS generation and lipoperoxidation in the bladder and kidney was also prevented by melatonin. Increased levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were detected in the MAB of cyclophosphamide-treated mice, all of which were prevented by melatonin. Functional assays using second-order mesenteric arteries of cyclophosphamide-treated mice revealed a decrease in vascular contractility. Melatonin prevented vascular hypocontractility in the cyclophosphamide group. Melatonin partially prevented the decrease in myeloperoxidase (MPO) and N-acetyl-beta-D-glucosaminidase (NAG) activities in the MAB of the cyclophosphamide group. SIGNIFICANCE: Melatonin may constitute a novel and promising therapeutic approach for management of the toxic effects induced by cyclophosphamide in the vasculature.

A two-generational reproductive study to assess the effects of Juglans regia on reproductive developments in the male and female rats.

Environmental pollutants and lifestyle severely threaten human and animal health, leading to disturbances of various functions, including infertility. So, exploring a safe treatment that could effectively reverse infertility remains a challenge. The current study was intended to explore the fertility-enhancing effect of Juglans Regia oil in two successive generations of rats; F0 and F1. J. Regia oil was initially tested for in vitro antioxidant assay via ROS and DPPH, followed by in vivo toxicity testing. In the fertility assessment, eighteen pairs of male and female rats (n=36, 1:1, F0 generation) were divided into three groups and dosed with 1 mL/kg and 2 mL/kg daily of J. Regia oil and saline, respectively, up to pre-cohabitation, cohabitation, gestation and lactation periods. The reproductive performance, including body weight, live birth index, fertility index, and litter size, was assessed. Hormonal and antioxidant markers of F1 generations were assessed with the histopathological evaluation of male and female organs. The oil of J. Regia showed great antioxidant potential (P < 0.05) in DPPH (1,1-diphenyl-2-picrylhydrazyl) and ROS (Reactive Oxygen Species) methods (P<0.05). The continued exposure of the F0 and F1 generations to J. Regia oil did not affect body weight, fertility index, litter size, and survival index. We have found pronounced fertility outcomes in both genders of F0 and F1 generations with J. Regia 2 mL/kg/day in comparison to the control. Results showed that J. Regia significantly increased (P < 0.05) luteinizing hormone (LH), plasma testosterone, follicular stimulating hormone (FSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities in both generations. Histology of both generations reveals improved spermatogenesis and folliculogenesis with enhanced architecture. Altogether, the present results suggest that J. Regia improved fertility in both male and female rats by improving hormonal activities and oxidative stress.

Increased Iron Levels and Oxidative Stress Mediate Age-Related Impairments in Male and Female Drosophila melanogaster.

Aging is characterized by a functional decline in the physiological functions and organic systems, causing frailty, illness, and death. Ferroptosis is an iron- (Fe-) dependent regulated cell death, which has been implicated in the pathogenesis of several disorders, such as cardiovascular and neurological diseases. The present study investigated behavioral and oxidative stress parameters over the aging of Drosophila melanogaster that, together with augmented Fe levels, indicate the occurrence of ferroptosis. Our work demonstrated that older flies (30-day-old) of both sexes presented impaired locomotion and balance when compared with younger flies (5-day-old). Older flies also produced higher reactive oxygen species (ROS) levels, decreased glutathione levels (GSH), and increased lipid peroxidation. In parallel, Fe levels were augmented in the fly's hemolymph. The GSH depletion with diethyl maleate potentiated the behavioral damage associated with age. Our data demonstrated biochemical effects that characterize the occurrence of ferroptosis over the age of D. melanogaster and reports the involvement of GSH in the age-associated damages, which could be in part attributed to the augmented levels of Fe.

Peroxiredoxin 5 overexpression decreases oxidative stress and dopaminergic cell death mediated by paraquat.

Peroxiredoxins (Prdxs) are thiol-dependent enzymes that scavenge peroxides. Previously, we found that Prdxs were hyperoxidized in a Parkinson's disease model induced by paraquat (PQ), which led to their inactivation, perpetuating reactive oxygen species (ROS) formation. Herein, we evaluated the redox state of the typical 2-Cys-Prx subgroup. We found that PQ induces ROS compartmentalization in different organelles, reflected by the 2-Cys-Prdx hyperoxidation pattern detected by redox eastern blotting. 2-Cys Prdxs are most vulnerable to hyperoxidation, while atypical 2-Cys Peroxiredoxin 5 (Prdx5) is resistant and is expressed in multiple organelles, such as mitochondria, peroxisomes, and cytoplasm. Therefore, we overexpressed human Prdx5 in the dopaminergic SHSY-5Y cell line using the adenoviral vector Ad-hPrdx5. Prdx5 overexpression was confirmed by western blotting and immunofluorescence (IF) and effectively decreased PQ-mediated mitochondrial and cytoplasmic ROS assessed with a mitochondrial superoxide indicator and DHE through IF or flow cytometry. Decreased ROS mediated by Prdx5 in the main subcellular compartments led to overall cell protection against PQ-induced cell death, which was demonstrated by flow cytometry using Annexin V labeling and 7-AAD. Therefore, Prdx5 is an attractive therapeutic target for PD, as its overexpression protects dopaminergic cells from ROS and death, which warrants further experimental animal studies for its subsequent application in clinical trials.

Biochemical and physiological effects of multigenerational exposure to spheric polystyrene microplastics in Caenorhabditis elegans.

Although studies have already shown the effects of exposure to microplastics (MP) in different species, the effects over generations in these individuals remain poorly understood. Therefore, the present study aimed to evaluate the effect of polystyrene MP (spherical, 1 µm) on the responses of the free-living nematode Caenorhabditis elegans in a multigenerational approach over five subsequent generations. MP concentrations of both 5 and 50 µg/L induced a detoxification response, increasing glutathione S-transferase (GST) activity and inducing the generation of reactive oxygen species (ROS) and lipid peroxidation (TBARS). MP also demonstrated the ability to accumulate in the animal's body during the 96 h of each generational exposure, and possibly, this constant interaction was the main reason for the decreased response in physiological parameters as in the exploratory behavior (body bending) of nematodes, and in the reproduction, being this last parameter most negatively affected during the five exposed generations, with a reduction of almost 50% in the last generation. These results emphasize the importance of multigenerational approaches, highlighting their advantage in the assessment of environmental contaminants.

Heavy metals and metalloids accumulation in common beans (Phaseolus vulgaris L.): A review.

Heavy metals (HMs) and metalloids (Ms) such as arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) represent serious environmental threats due to their wide abundance and high toxicity. Contamination of water and soils by HMs and Ms from natural or anthropogenic sources is of great concern in agricultural production due to their toxic effects on plants, adversely affecting food safety and plant growth. The uptake of HMs and Ms by Phaseolus vulgaris L. plants depends on several factors including soil properties such as pH, phosphate, and organic matter. High concentrations of HMs and Ms could be toxic to plants due to the increased generation of reactive oxygen species (ROS) such as (O2•-), (•OH), (H2O2), and (1O2), and oxidative stress due to an imbalance between ROS generation and antioxidant enzyme activity. To minimize the effects of ROS, plants have developed a complex defense mechanism based on the activity of antioxidant enzymes such as SOD, CAT, GPX, and phytohormones, especially salicylic acid (SA) that can reduce the toxicity of HMs and Ms. This review focuses on evaluating the accumulation and translocation of As, Cd, Hg, and Pb in Phaseolus vulgaris L. plants and on their possible effects on the growth of Phaseolus vulgaris L. in soil contaminated with these elements. The factors that affect the uptake of HMs and Ms by bean plants, and the defense mechanisms under oxidative stress caused by the presence of As, Cd, Hg, and Pb are also discussed. Furthermore, future research on mitigating HMs and Ms toxicity in Phaseolus vulgaris L. plants is highlighted.

Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells.

Skin cancer has high rates of mortality and therapeutic failure. In this study, to develop a multi-agent strategy for skin cancer management, the selective cytotoxicity of several alkaloid fractions and pure alkaloids isolated from Amaryllidaceae species was evaluated in melanoma cells. In addition, UVB-stimulated keratinocytes (HaCaT) were exposed to seven alkaloid fractions characterized by GC-MS, and the production of intracellular reactive oxygen species (ROS) and IL-6, were measured to evaluate their photoprotection effects. The Eucharis caucana (bulb) alkaloid fraction (20 µg/ml) had a clear effect on the viability of melanoma cells, reducing it by 45.7% without affecting healthy keratinocytes. This alkaloid fraction and tazettine (both at 2.5 µg/ml) suppressed UVB-induced ROS production by 31.6% and 29.4%, respectively. The highest anti-inflammatory potential was shown by the Zephyranthes carinata (bulb) alkaloid fraction (10 µg/ml), which reduced IL-6 production by 90.8%. According to the chemometric analysis, lycoramine and tazettine had a photoprotective effect on the UVB-exposed HaCaT cells, attenuating the production of ROS and IL-6. These results suggest that Amaryllidaceae alkaloids have photoprotective and therapeutic potential in skin cancer management, especially at low concentrations.

LOX-1 Activation by oxLDL Induces AR and AR-V7 Expression via NF-κB and STAT3 Signaling Pathways Reducing Enzalutamide Cytotoxic Effects.

The oxidized low-density lipoprotein receptor 1 (LOX-1) is one of the most important receptors for modified LDLs, such as oxidated (oxLDL) and acetylated (acLDL) low-density lipoprotein. LOX-1 and oxLDL are fundamental in atherosclerosis, where oxLDL/LOX1 promotes ROS generation and NF-κB activation inducing the expression of IL-6, a STAT3 activator. Furthermore, LOX-1/oxLDL function has been associated with other diseases, such as obesity, hypertension, and cancer. In prostate cancer (CaP), LOX-1 overexpression is associated with advanced stages, and its activation by oxLDL induces an epithelial-mesenchymal transition, increasing angiogenesis and proliferation. Interestingly, enzalutamide-resistant CaP cells increase the uptake of acLDL. Enzalutamide is an androgen receptor (AR) antagonist for castration-resistant prostate cancer (CRPC) treatment, and a high percentage of patients develop a resistance to this drug. The decreased cytotoxicity is promoted in part by STAT3 and NF-κB activation that induces the secretion of the pro-inflammatory program and the expression of AR and its splicing variant AR-V7. Here, we demonstrate for the first time that oxLDL/LOX-1 increases ROS levels and activates NF-κB, inducing IL-6 secretion and the activation of STAT3 in CRPC cells. Furthermore, oxLDL/LOX1 increases AR and AR-V7 expression and decreases enzalutamide cytotoxicity in CRPC. Thus, our investigation suggests that new factors associated with cardiovascular pathologies, such as LOX-1/oxLDL, may also promote important signaling axes for the progression of CRPC and its resistance to drugs used for its treatment.

Alpha-lipoic acid improves bovine preimplantation blastocyst quality and cryotolerance.

In vitro embryo production has grown in recent decades due to its great potential for cattle production. However, the quality of in vitro-produced embryos is lower compared with those produced in vivo. The postfertilization culture environment has a major influence on bovine embryo quality. We hypothesize that the inclusion of the inclusion of alpha-lipoic acid (ALA) in the in vitro culture (IVC) medium during the first 24 h would have positive effects on embryo development in vitro and cryotolerance. The aims of this study were to evaluate the antioxidant effect of ALA in IVC medium for 24 h on bovine zygotes (21 h post in vitro fertilization, IVF), day 2 cleaved embryos (46 h post-IVF), and to assess embryo quality, developmental competence, and cryotolerance after vitrification. In all experiments, IVC medium was the Control, and 2.5 µM ALA was the treatment implemented. Viability and reactive oxygen species (ROS) levels in zygotes and day 2 embryos did not differ from the Control (P > 0.05). Supplementation with ALA increased total blastocyst and hatching rates (P < 0.05). It also improved embryo quality, evidenced by the increased blastocyst total cell number and the percentage of excellent-quality embryos observed (P < 0.05). In embryos cultured with ALA and then vitrified, ALA reduced intracellular ROS levels in warmed blastocysts (P < 0.05). In conclusion, ALA supplementation to IVC medium during 24 h is a new advantage in improving embryo quality for assisted bovine reproduction.

The first evidence of antibiofilm action of Proteus mirabilis with tetra-cationic porphyrins containing cisplatin by antimicrobial photodynamic therapy.

Biofilms are responsible for up to 80% of antimicrobial-resistant nosocomial infections. Most of these infections are associated with medical devices such as urinary catheters, and in this context, it is estimated that 90-100% of patients who undergo long-term catheterization develop infections. Proteus mirabilis, the most prevalent microorganism, is responsible for 20-45% of these infections. Thus, this study aimed to evaluate, for the first time, the antimicrobial and antibiofilm effects of cationic porphyrins on P. mirabilis. Neutral porphyrins 3-H2TPyP and 4-H2TpyP and tetra-cationic derivatives 3-cis-PtTPyP and 4-cis-PtTPyP were evaluated in broth microdilution tests to determine the minimum inhibitory and bactericidal concentrations. Time-kill curves, checkerboard test, reactive oxygen species (ROS) scavenger assays, conventional biofilm formation, and biofilm assay with catheters were also performed. The microdilution tests showed greater efficacy against P. mirabilis when 3-cis-PtTPyP was exposed to white-light conditions; this also occurred when the microbial time-kill curve was performed at 0, 2, 6, and 12 h. The radical superoxide species was possibly responsible for photoinactivation in the ROS scavenger assays. In biofilm assays (conventional and catheter), 3-cis-PtTPyP obtained better results when irradiated with a white-light source. In the checkerboard assay, the same compound showed no differences when tested in association with ciprofloxacin hydrochloride. Our findings lead us to conclude that antimicrobial photodynamic therapy and cationic porphyrins obtained positive results and are promising alternatives to treat P. mirabilis biofilms.

Antimicrobial and Photoantimicrobial Activities of Chitosan/CNPPV Nanocomposites.

Multidrug-resistant bacteria represent a global health and economic burden that urgently calls for new technologies to combat bacterial antimicrobial resistance. Here, we developed novel nanocomposites (NCPs) based on chitosan that display different degrees of acetylation (DAs), and conjugated polymer cyano-substituted poly(p-phenylene vinylene) (CNPPV) as an alternative approach to inactivate Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria. Chitosan's structure was confirmed through FT-Raman spectroscopy. Bactericidal and photobactericidal activities of NCPs were tested under dark and blue-light irradiation conditions, respectively. Hydrodynamic size and aqueous stability were determined by DLS, zeta potential (ZP) and time-domain NMR. TEM micrographs of NCPs were obtained, and their capacity of generating reactive oxygen species (ROS) under blue illumination was also characterized. Meaningful variations on ZP and relaxation time T2 confirmed successful physical attachment of chitosan/CNPPV. All NCPs exhibited a similar and shrunken spherical shape according to TEM. A lower DA is responsible for driving higher bactericidal performance alongside the synergistic effect from CNPPV, lower nanosized distribution profile and higher positive charged surface. ROS production was proportionally found in NCPs with and without CNPPV by decreasing the DA, leading to a remarkable photobactericidal effect under blue-light irradiation. Overall, our findings indicate that chitosan/CNPPV NCPs may constitute a valuable asset for the development of innovative strategies for inactivation and/or photoinactivation of bacteria.

Mechanism of Antifungal Action of Monoterpene Isoespintanol against Clinical Isolates of Candida tropicalis.

The growing increase in infections by Candida spp., non-albicans, coupled with expressed drug resistance and high mortality, especially in immunocompromised patients, have made candidemia a great challenge. The efficacy of compounds of plant origin with antifungal potential has recently been reported as an alternative to be used. Our objective was to evaluate the mechanism of the antifungal action of isoespintanol (ISO) against clinical isolates of Candida tropicalis. Microdilution assays revealed fungal growth inhibition, showing minimum inhibitory concentration (MIC) values between 326.6 and 500 µg/mL. The eradication of mature biofilms by ISO was between 20.3 and 25.8% after 1 h of exposure, being in all cases higher than the effect caused by amphotericin B (AFB), with values between 7.2 and 12.4%. Flow cytometry showed changes in the permeability of the plasma membrane, causing loss of intracellular material and osmotic balance; transmission electron microscopy (TEM) confirmed the damage to the integrity of the plasma membrane. Furthermore, ISO induced the production of intracellular reactive oxygen species (iROS). This indicates that the antifungal action of ISO is associated with damage to membrane integrity and the induction of iROS production, causing cell death.

Antioxidant Effect of Coenzyme Q10 in the Prevention of Oxidative Stress in Arsenic-Treated CHO-K1 Cells and Possible Participation of Zinc as a Pro-Oxidant Agent.

Oxidative stress is an imbalance between levels of reactive oxygen species (ROS) and antioxidant enzymes. Compounds with antioxidant properties, such as coenzyme Q10 (CoQ10), can reduce cellular imbalance caused by an increase in ROS. CoQ10 participates in modulating redox homeostasis due to its antioxidant activity and its preserving mitochondrial functions. Thus, the present study demonstrated the protective effects of CoQ10 against oxidative stress and cytotoxicity induced by arsenic (As). Antioxidant capacity, formation of hydroperoxides, generation of ROS, and the effect on cellular viability of CoQ10, were investigated to determine the protective effect of CoQ10 against As and pro-oxidant compounds, such as zinc. Cell viability assays showed that CoQ10 is cytoprotective under cellular stress conditions, with potent antioxidant activity, regardless of the concentration tested. Zn, when used at higher concentrations, can increase ROS and show a pro-oxidant effect causing cell damage. The cytotoxic effect observed for As, Zn, or the combination of both could be prevented by CoQ10, without any decrease in its activity at cellular levels when combined with Zn.

Oxidative stress induction by crude extract of Xylaria sp. triggers lethality in the larvae of Aedes aegypti (Diptera: Culicidae).

BACKGROUND: Aedes aegypti is currently controlled with synthetic larvicides; however, mosquitoes have become highly resistant to these larvicides and difficult to eradicate. Studies have shown that insecticides derived from fungal extracts have various mechanisms of action that reduce the risk of resistance in these mosquitoes. One possible mechanism is uncontrolled production of reactive oxygen species (ROS) in the larvae, which can cause changes at the cellular level. Thus, the crude extract of Xylaria sp. was evaluated to investigate the oxidative effect of this extract in A. aegypti larvae by quantifying the oxidative damage to proteins and lipids. METHODS: The larvicidal potential of the crude extract of Xylaria sp. Was evaluated, and the extract was subsequently tested in human lung fibroblasts for cytotoxicity and ROS production. ROS level was quantified in the larvae that were killed following exposure to the extract in the larvicide test. RESULTS: The crude extract of Xylaria sp. Caused cytotoxicity and induced ROS production in human lung fibroblasts and A. aegypti larvae, respectively. In the larvicide trial, the extract showed an LC50 of 264.456 ppm and an LC90 of 364.307 ppm, and was thus considered active. The extract showed greater oxidative damage to lipids and proteins, with LC90 values of 24.7 µmol MDA/L and 14.6278 ×10-3 nmol carbonyl/ mg protein, respectively. CONCLUSIONS: Crude extracts of Xylaria sp. induced oxidative stress that may have caused the mortality of A. aegypti larvae.

Effects of Baru Almond Oil (Dipteryx alata Vog.) Treatment on Thrombotic Processes, Platelet Aggregation, and Vascular Function in Aorta Arteries.

Background: This study assessed the effects of Baru (Dipteryx alata Vog.) almond oil supplementation on vascular function, platelet aggregation, and thrombus formation in aorta arteries of Wistar rats. Methods: Male Wistar rats were allocated into three groups. The control group (n = 6), a Baru group receiving Baru almond oil at 7.2 mL/kg/day (BG 7.2 mL/kg, n = 6), and (iii) a Baru group receiving Baru almond oil at 14.4 mL/kg/day (BG 14.4 mL/kg, n = 6). Baru oil was administered for ten days. Platelet aggregation, thrombus formation, vascular function, and reactive oxygen species production were evaluated at the end of treatment. Results: Baru oil supplementation reduced platelet aggregation (p < 0.05) and the production of the superoxide anion radical in platelets (p < 0.05). Additionally, Baru oil supplementation exerted an antithrombotic effect (p < 0.05) and improved the vascular function of aorta arteries (p < 0.05). Conclusion: The findings showed that Baru oil reduced platelet aggregation, reactive oxygen species production, and improved vascular function, suggesting it to be a functional oil with great potential to act as a novel product for preventing and treating cardiovascular disease.

Moderate exercise combined with metformin-treatment improves mitochondrial bioenergetics of the quadriceps muscle of old female Wistar rats.

Sarcopenia is a syndrome that leads to physical disability and that deteriorates elderly people´s life quality. The etiology of sarcopenia is multifactorial, but mitochondrial dysfunction plays a paramount role in this pathology. Our research group has shown that the combined treatment of metformin (MTF) and exercise has beneficial effects for preventing muscle loss and fat accumulation, by modulating the redox state. To get an insight into the mechanism of the combined treatment, the mitochondrial bioenergetics was studied in the mitochondria isolated from old female Wistar rats quadriceps muscles. The animals were divided into six groups; three performed exercise on a treadmill for 5 days/week for 20 months, and the other three were sedentary. Also, two groups of each were treated with MTF for 6 or 12 months. The rats were euthanized at 24 months. The mitochondria were isolated and supercomplexes formation along with oxygen consumption, ATP synthesis, and ROS generation were evaluated. Our results showed that the combined treatment for 12 months increased the complex I and IV activities associated with the supercomplexes, simultaneously, ATP synthesis increased while ROS production decreased, indicating a tightly coupled mitochondria. The role of exercise plus the MTF treatment against sarcopenia in old muscles is discussed.

Antioxidant therapy reverses sympathetic dysfunction, oxidative stress, and hypertension in male hyperadipose rats.

AIMS: The rostral ventrolateral medulla (RVLM) is the main sympathetic output of the central nervous system to control blood pressure. Reportedly, reactive oxygen species (ROS) can increase arterial pressure, leading to hypertension. As ROS increase the sympathetic tone in RVLM and obese animals present grater oxidative stress, it would be important to note this relationship. MAIN METHODS: Therefore, we evaluated the systemic and central effects (in the RVLM) of vitamin C (vit C, an antioxidant) on the redox balance and cardiovascular and autonomic profiles in hyperadipose male rats. We also evaluated the neurotransmission by L-glutamate (L-glu) and vit C in the RVLM of awake hyperadipose rats. KEY FINDINGS: Our study confirmed that hyperadipose rats were hypertensive and tachycardic, presented increased sympathetic and decreased parasympathetic modulation of the heart, and had increased plasma lipoperoxidation compared with the control rats (CTR). Oral vitamin C treatment reverted cardiovascular, autonomic, and plasma redox dysfunction. Hyperadipose rats presented a higher blood pressure increase after L-glu microinjection and a lower response to vit C in the RVLM compared with the CTR group. Biochemical analysis of redox balance in RVLM punches showed that hyperadipose rats have increased NBT and T-BARS, and after treatment with vit C, the oxidative profile decreased. The antioxidative activity of vit C reduced the amount of ROS in the RVLM area that might have resulted in lowered blood pressure and sympathetic modulation. SIGNIFICANCE: Our data suggest central and peripheral benefits of vit C treatment on cardiovascular, autonomic, and oxidative dysfunctions in hyperadipose animals.

Octyl gallate decrease lymphocyte activation and regulates neutrophil extracellular traps release.

BACKGROUND: Inflammation is a complex mechanism with an objective to destroy and eliminate the invading microorganisms. During acute inflammation, the neutrophils are the major cells involved in this process and, although they defend the organism, must die to not generate damage. The two major mechanisms that drive neutrophils to death are: apoptosis and a novel mechanism recently discovered denominated NETosis. This process is a "suicidal mechanism", in which the cells release "neutrophil extracellular traps" (NETs) during the inflammatory response. Octyl gallate (OG) is one of the gallic acid derivates, with several protective effects, such as antioxidant and anti-inflammatory in cancer models. Thus, this study aimed to investigate the action of OG on the proliferation of lymphocytes, neutrophils activation, and its effectiveness in an experimental sepsis model. METHODS: Lymphocytes and neutrophils were obtained from healthy donors. Cell viability, apoptosis, NETs release and antioxidant capacity of OG were observed. In addition, survival was evaluated in an experimental model of sepsis in C57BL/6 mice. RESULTS: Our study demonstrated, for the first time, that the OG can act as an inhibitor of reactive oxygen species (ROS) release, NETs formation in primary human neutrophils and, modulates the lipopolysaccharide (LPS) effect in neutrophil apoptosis. The OG also inhibited peripheral blood mononuclear cells (PBMCs) proliferation in vitro. Despite the positive results, we did not observe an increase in the survival of septic animals. CONCLUSIONS: The pharmacological potential of OG, modulating activation of neutrophils and lymphocytes, suggests the use as an adjuvant therapeutic strategy in inflammatory diseases.

The Protective Effect of Kaempferol Against Ischemia/Reperfusion Injury Through Activating SIRT3 to Inhibit Oxidative Stress.

INTRODUCTION: The objective of this study is to investigate the protective effect of kaempferol against ischemia/reperfusion (IR) injury and the underlying molecular mechanisms. METHODS: H9C2 cells were pretreated with kaempferol for 24 hours and further insulted with IR injury. Cell vitality, reactive oxygen species (ROS) level, glutathione (GSH) level, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and sirtuin-3 (SIRT3), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) expressions were evaluated. Moreover, short interfering ribonucleic acid targeting SIRT3 was used to investigate the role of SIRT3 against IR mediated by kaempferol in vitro. IR mice models were also established to confirm the protective effects of kaempferol on IR in vivo. RESULTS: After IR injury, H9C2 cells vitality was reduced, ROS levels, NADPH oxidase activity, and Bax expressions were increased, and GSH levels and Bcl2 expressions were decreased. After kaempferol pretreatment, the vitality of H9C2 cells was increased. The levels of ROS, NADPH oxidase activity, and Bax expression were decreased. In addition, levels of GSH and Bcl2 expression were enhanced. Furthermore, silencing SIRT3 attenuated the protective effect mediated by kaempferol, with increased ROS levels, NADPH oxidase activity, and Bax expression, along with reduced GSH level and Bcl2 expression. In vivo IR model showed that kaempferol could preserve IR-damaged cardiac function. CONCLUSION: Kaempferol has the capability of attenuating H9C2 cells IR injury through activating SIRT3 to inhibit oxidative stress.