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19 pages, 2611 KiB

Open AccessArticle

Pinus halepensis Essential Oil Ameliorates Aβ1-42-Induced Brain Injury by Diminishing Anxiety, Oxidative Stress, and Neuroinflammation in Rats

by Paula Alexandra Postu, Marius Mihasan, Dragos Lucian Gorgan, Fatima Zahra Sadiki, Mostafa El Idrissi and Lucian Hritcu

Biomedicines 2022, 10(9), 2300; https://doi.org/10.3390/biomedicines10092300 - 16 Sep 2022

Cited by 3 | Viewed by 2279

Abstract

The Pinus L. genus comprises around 250 species, being popular worldwide for their medicinal and aromatic properties. The present study aimed to evaluate the P. halepensis Mill. essential oil (PNO) in an Alzheimer’s disease (AD) environment as an anxiolytic and antidepressant agent. The [...] Read more.

The Pinus L. genus comprises around 250 species, being popular worldwide for their medicinal and aromatic properties. The present study aimed to evaluate the P. halepensis Mill. essential oil (PNO) in an Alzheimer’s disease (AD) environment as an anxiolytic and antidepressant agent. The AD-like symptoms were induced in Wistar male rats by intracerebroventricular administration of amyloid beta1-42 (Aβ1-42), and PNO (1% and 3%) was delivered to Aβ1-42 pre-treated rats via inhalation route for 21 consecutive days, 30 min before behavioral assessments. The obtained results indicate PNO’s potential to relieve anxious–depressive features and to restore redox imbalance in the rats exhibiting AD-like neuropsychiatric impairments. Moreover, PNO presented beneficial effects against neuroinflammation and neuroapoptosis in the Aβ1-42 rat AD model. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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14 pages, 926 KiB

Open AccessArticle

TMT-Based Proteomic Analysis of Human Spermatozoa from Unexplained Recurrent Miscarriage Patients before and after Oral Antioxidant Treatment

by Alba Fernandez-Encinas, Jordi Ribas-Maynou, Agustín García-Peiró, Sergio Garcia-Segura, Olga Martinez-Pasarell, Joaquima Navarro, Maria Oliver-Bonet and Jordi Benet

Biomedicines 2022, 10(8), 2014; https://doi.org/10.3390/biomedicines10082014 - 19 Aug 2022

Cited by 4 | Viewed by 1661

Abstract

Recently, sperm quality and the presence of double-stranded breaks (DSB) has been pointed out as a possible cause of recurrent miscarriage, and the use of antioxidants has expanded as a treatment for male infertility. The aim of the present study was to analyze [...] Read more.

Recently, sperm quality and the presence of double-stranded breaks (DSB) has been pointed out as a possible cause of recurrent miscarriage, and the use of antioxidants has expanded as a treatment for male infertility. The aim of the present study was to analyze the proteomic effects of antioxidants on sperm from RM patients with high incidence of DSB. Proteomic analysis was performed using a tandem mass tag labeling technique, and subsequently compared with the PANTHER database for DEPs, and the STRING database for protein–protein interactions (PPI). Differentially expressed proteins (DEPs) both before and after antioxidant oral treatment were identified. PPI involving DEPs clustered into networks related to cell metabolism, cytoskeleton, and DNA damage. Results show that the sperm proteomic profiles before and after antioxidant treatment do not significantly differ from each other. However, some DEPs found after the antioxidant treatment shifted towards a DEPs profile typical of fertile donors. This indirect measurement suggests an improvement caused by antioxidants on the expression of several proteins. Among them were proteins involved in sperm DNA remodeling (LMO7, MMP28, BNC2, H2B, and PRDM2). The results presented here represent the first approach in the analysis and repair of the proteomic change caused by antioxidants in recurrent miscarriage patients, elucidating biomarkers that may be useful for the diagnosis and further sperm selection in this type of patient. Further studies should be conducted to validate the usefulness of these biomarkers in larger study groups. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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16 pages, 3836 KiB

Open AccessArticle

Inflammation of the Human Dental Pulp Induces Phosphorylation of eNOS at Thr495 in Blood Vessels

by Özlem Erdek, Wilhelm Bloch, Svenja Rink-Notzon, Hubert C. Roggendorf, Senem Uzun, Britta Meul, Manuel Koch, Jörg Neugebauer, James Deschner and Yüksel Korkmaz

Biomedicines 2022, 10(7), 1586; https://doi.org/10.3390/biomedicines10071586 - 03 Jul 2022

Cited by 3 | Viewed by 2096

Abstract

The activity of endothelial nitric oxide synthase (eNOS) in endothelial cells increased with the phosphorylation of the enzyme at Ser1177 and decreased at Thr495. The regulation of the phosphorylation sites of eNOS at Ser1177 and Thr495 in blood vessels of the healthy and [...] Read more.

The activity of endothelial nitric oxide synthase (eNOS) in endothelial cells increased with the phosphorylation of the enzyme at Ser1177 and decreased at Thr495. The regulation of the phosphorylation sites of eNOS at Ser1177 and Thr495 in blood vessels of the healthy and inflamed human dental pulp is unknown. To investigate this, healthy and carious human third molars were immersion-fixed and decalcified. The localization of eNOS, Ser1177, and Thr495 in healthy and inflamed blood vessels was examined in consecutive cryo-sections using quantitative immunohistochemical methods. We found that the staining intensity of Ser1177 in healthy blood vessels decreased in inflamed blood vessels, whereas the weak staining intensity of Thr495 in healthy blood vessels strongly increased in inflamed blood vessels. In blood vessels of the healthy pulp, eNOS is active with phosphorylation of the enzyme at Ser1177. The phosphorylation of eNOS at Thr495 in inflamed blood vessels leads to a decrease in eNOS activity, contributing to eNOS uncoupling and giving evidence for a decrease in NO and an increase in O₂⁻ production. Since the formation of the tertiary dentin matrix depends on intact pulp circulation, eNOS uncoupling and phosphorylation of eNOS at Thr495 in the inflamed pulp blood vessels should be considered during caries therapy. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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17 pages, 2210 KiB

Open AccessArticle

Phthalate Exposure and Oxidative/Nitrosative Stress in Childhood Asthma: A Nested Case-Control Study with Propensity Score Matching

by Jung-Wei Chang, Hsin-Chang Chen, Heng-Zhao Hu, Wan-Ting Chang, Po-Chin Huang and I-Jen Wang

Biomedicines 2022, 10(6), 1438; https://doi.org/10.3390/biomedicines10061438 - 17 Jun 2022

Cited by 4 | Viewed by 1997

Abstract

Whether low-dose phthalate exposure triggers asthma among children, and its underlying mechanisms, remain debatable. Here, we evaluated the individual and mixed effects of low-dose phthalate exposure on children with asthma and five (oxidative/nitrosative stress/lipid peroxidation) mechanistic biomarkers—8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO₂Gua), 4-hydroxy-2-nonenal-mercapturic [...] Read more.

Whether low-dose phthalate exposure triggers asthma among children, and its underlying mechanisms, remain debatable. Here, we evaluated the individual and mixed effects of low-dose phthalate exposure on children with asthma and five (oxidative/nitrosative stress/lipid peroxidation) mechanistic biomarkers—8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO₂Gua), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), 8-isoprostaglandin F2α (8-isoPF2α), and malondialdehyde (MDA)—using a propensity score-matched case-control study (case vs. control = 41 vs. 111). The median monobenzyl phthalate (MBzP) concentrations in the case group were significantly higher than those in the control group (3.94 vs. 2.52 ng/mL, p = 0.02), indicating that dust could be an important source. After adjustment for confounders, the associations of high monomethyl phthalate (MMP) (75th percentile) with 8-NO₂Gua (adjusted odds ratio (aOR): 2.66, 95% confidence interval (CI): 1.03–6.92) and 8-isoPF2α (aOR: 4.04, 95% CI: 1.51–10.8) and the associations of mono-iso-butyl phthalate (MiBP) with 8-isoPF2α (aOR: 2.96, 95% CI: 1.13–7.79) were observed. Weighted quantile sum regression revealed that MBzP contributed more than half of the association (56.8%), followed by MiBP (26.6%) and mono-iso-nonyl phthalate (MiNP) (8.77%). Our findings supported the adjuvant effect of phthalates in enhancing the immune system response. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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16 pages, 1470 KiB

Open AccessArticle

Different Changes in Adipokines, Lipid Profile, and TNF-Alpha Levels between 10 and 20 Whole Body Cryostimulation Sessions in Individuals with I and II Degrees of Obesity

by Wanda Pilch, Anna Piotrowska, Joanna Wyrostek, Olga Czerwińska-Ledwig, Ewa Ziemann, Jędrzej Antosiewicz, Mariusz Zasada, Małgorzata Kulesa-Mrowiecka and Małgorzata Żychowska

Biomedicines 2022, 10(2), 269; https://doi.org/10.3390/biomedicines10020269 - 26 Jan 2022

Cited by 11 | Viewed by 2414

Abstract

Obesity is associated with chronic inflammation. While cold therapy influences the pro/antioxidative status of an individual, by affecting adipokine levels and the lipid profile, the effect of body mass index (BMI) on the response to cold exposure is unclear. We analyzed the link [...] Read more.

Obesity is associated with chronic inflammation. While cold therapy influences the pro/antioxidative status of an individual, by affecting adipokine levels and the lipid profile, the effect of body mass index (BMI) on the response to cold exposure is unclear. We analyzed the link between BMI and the differences in effects of whole-body stimulation, depending on the number of treatments, on specific physiological parameters in men. Twenty-seven non-active men were divided into three groups: N (n = 9, BMI < 24.9), IOb (n = 9, BMI 30.0–34.9), and IIOb (BMI ≥ 35.0). The subjects participated in 20 3-min cryochamber sessions (−120 °C), 1/day, 5 days/week. Body composition was analyzed before and after treatment. Blood adiponectin (ADP), leptin (LEP), and tumor necrosis factor alpha (TNF-alpha) levels, and the lipid profile were analyzed three times: at baseline and up to 2 h after 10 and 20 sessions. The 20 treatments caused significant changes in body composition. Between 10 and 20 whole-body cryostimulation (WBC) sessions, a significant decreased was observed in the LEP and TNF-alpha levels. No significant changes in the lipid profile were noted. However, a positive tendency to regain the metabolic balance in adipose tissue was apparent in the IOb group in the tested period (decreased TG levels, increased HDL levels or the HDL/LDL ratio, and significantly decreased visceral adiposity index levels). Collectively, for people with obesity increasing the number of treatments above the standard 10 should be recommended. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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22 pages, 4652 KiB

Open AccessArticle

Microtubule Affinity-Regulating Kinase 4 Promotes Oxidative Stress and Mitochondrial Dysfunction by Activating NF-κB and Inhibiting AMPK Pathways in Porcine Placental Trophoblasts

by Liang Tian, Guangfan Liu, Ziqi Kang and Peishi Yan

Biomedicines 2022, 10(1), 165; https://doi.org/10.3390/biomedicines10010165 - 13 Jan 2022

Cited by 5 | Viewed by 1772

Abstract

The aim of this investigation was to evaluate the role of MARK4 in the regulation of oxidative stress and mitochondrial dysfunction in pig placental trophoblasts and analyze the signaling pathways involved. In this study, we found that enhanced MARK4 contributed to augmented oxidative [...] Read more.

The aim of this investigation was to evaluate the role of MARK4 in the regulation of oxidative stress and mitochondrial dysfunction in pig placental trophoblasts and analyze the signaling pathways involved. In this study, we found that enhanced MARK4 contributed to augmented oxidative stress in pig trophoblasts, as evidenced by decreased total antioxidant capacity (TAC); higher production of reactive oxygen species (ROS); elevated protein carbonylation; and reduced SOD, CAT, and GSH-PX activities. Further analyses revealed MARK4 impaired mitochondrial oxidative respiration in cultured trophoblasts, which was associated with reduced ATP content, decreased mitochondrial membrane potential, lower mitochondrial Complexes I and III activities, and down-regulated protein contents of subunits of complexes I, II, and V. At same time, mitochondrial biogenesis and structure were negatively altered by elevated MARK4. By antioxidant treatment with vitamin E (VE), oxidative stress along with impaired mitochondrial function induced by enhanced MARK4 were blocked. Furthermore, we found activation of AMPK signaling prevented MARK4 from blocking mitochondrial biogenesis and function in pig trophoblast cells. Finally, we demonstrated that the IKKα/NF-κB signal pathway was involved in MARK4 activated oxidative stress and mitochondrial dysfunction. Thus, these data suggest that MARK4 promotes oxidative stress and mitochondrial injury in porcine placental trophoblasts and can contribute to the developing of knowledge of pathological processes leading to mitochondrial dysfunction associated with excessive back-fat in the pig placenta and to the obesity-associated pregnant syndrome. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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14 pages, 2854 KiB

Open AccessArticle

Canthaxanthin Biofabrication, Loading in Green Phospholipid Vesicles and Evaluation of In Vitro Protection of Cells and Promotion of Their Monolayer Regeneration

by Ines Castangia, Maria Letizia Manca, Seyed Hadi Razavi, Amparo Nácher, Octavio Díez-Sales, José Esteban Peris, Mohamad Allaw, Maria Carmen Terencio, Iris Usach and Maria Manconi

Biomedicines 2022, 10(1), 157; https://doi.org/10.3390/biomedicines10010157 - 12 Jan 2022

Cited by 7 | Viewed by 1578

Abstract

In the present study, canthaxanthin was produced by biofermentation from Dietzia natronolimnaea HS-1 (D. natronolimnaea) and was loaded in phospholipid vesicles prepared with natural component using an easy and low dissipative method. Indeed, glycerosomes, hyalurosomes, and glycerohyalurosomes were prepared by direct hydration of [...] Read more.

In the present study, canthaxanthin was produced by biofermentation from Dietzia natronolimnaea HS-1 (D. natronolimnaea) and was loaded in phospholipid vesicles prepared with natural component using an easy and low dissipative method. Indeed, glycerosomes, hyalurosomes, and glycerohyalurosomes were prepared by direct hydration of both phosphatidylcholine and the biotechnological canthaxanthin, avoiding the use of organic solvents. Vesicles were sized from 63 nm to 87 nm and highly negatively charged. They entrapped a high number of the biomolecules and were stable on storage. Canthaxanthin-loaded vesicles incubated with fibroblasts did not affect their viability, proving to be highly biocompatible and capable of inhibiting the death of fibroblasts stressed with hydrogen peroxide. They reduced the nitric oxide expression in macrophages treated with lipopolysaccharides. Moreover, they favoured the cell migration in an in vitro lesion model. Results confirmed the health-promoting potential of canthaxanthin in skin cells, which is potentiated by its suitable loading in phospholipid vesicles, thus suggesting the possible use of these natural bioformulations in both skin protection and regeneration, thanks to the potent antioxidant, anti-inflammatory and antiageing effects of canthaxanthin. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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13 pages, 4195 KiB

Open AccessArticle

The Salutary Effects of Catalpol on Diesel Exhaust Particles-Induced Thrombogenic Changes and Cardiac Oxidative Stress, Inflammation and Apoptosis

by Abderrahim Nemmar, Sumaya Beegam, Nur Elena Zaaba, Salem Alblooshi, Saleh Alseiari and Badreldin H. Ali

Biomedicines 2022, 10(1), 99; https://doi.org/10.3390/biomedicines10010099 - 04 Jan 2022

Cited by 7 | Viewed by 1739

Abstract

Inhaled particulate air pollution exerts pulmonary inflammation and cardiovascular toxicity through secondary systemic effects due to oxidative stress and inflammation. Catalpol, an iridiod glucoside, extracted from the roots of Rehmannia glutinosa Libosch, has been reported to possess anti-inflammatory and antioxidant properties. Yet, the [...] Read more.

Inhaled particulate air pollution exerts pulmonary inflammation and cardiovascular toxicity through secondary systemic effects due to oxidative stress and inflammation. Catalpol, an iridiod glucoside, extracted from the roots of Rehmannia glutinosa Libosch, has been reported to possess anti-inflammatory and antioxidant properties. Yet, the potential ameliorative effects of catalpol on particulate air pollution—induced cardiovascular toxicity, has not been studied so far. Hence, we evaluated the possible mitigating mechanism of catalpol (5 mg/kg) which was administered to mice by intraperitoneal injection one hour before the intratracheal (i.t.) administration of a relevant type of pollutant particle, viz. diesel exhaust particles (DEPs, 30 µg/mouse). Twenty-four hours after the lung deposition of DEPs, several cardiovascular endpoints were evaluated. DEPs caused a significant shortening of the thrombotic occlusion time in pial microvessels in vivo, induced platelet aggregation in vitro, and reduced the prothrombin time and the activated partial thromboplastin time. All these actions were effectively mitigated by catalpol pretreatment. Likewise, catalpol inhibited the increase of the plasma concentration of C-reactive proteins, fibrinogen, plasminogen activator inhibitor-1 and P- and E-selectins, induced by DEPs. Moreover, in heart tissue, catalpol inhibited the increase of markers of oxidative (lipid peroxidation and superoxide dismutase) and nitrosative (nitric oxide) stress, and inflammation (tumor necrosis factor α, interleukin (IL)-6 and IL-1β) triggered by lung exposure to DEPs. Exposure to DEPs also caused heart DNA damage and increased the levels of cytochrome C and cleaved caspase, and these effects were significantly diminished by the catalpol pretreatment. Moreover, catalpol significantly reduced the DEPs-induced increase of the nuclear factor κB (NFκB) in the heart. In conclusion, catalpol significantly ameliorated DEPs–induced procoagulant events and heart oxidative and nitrosative stress, inflammation, DNA damage and apoptosis, at least partly, through the inhibition of NFκB activation. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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14 pages, 3970 KiB

Open AccessArticle

Curcumin Nanoparticles Enhance Antioxidant Efficacy of Diclofenac Sodium in Experimental Acute Inflammation

by Ioana Boarescu, Paul-Mihai Boarescu, Raluca Maria Pop, Ioana Corina Bocșan, Dan Gheban, Ruxandra-Mioara Râjnoveanu, Armand Râjnoveanu, Adriana Elena Bulboacă, Anca Dana Buzoianu and Sorana D. Bolboacă

Biomedicines 2022, 10(1), 61; https://doi.org/10.3390/biomedicines10010061 - 28 Dec 2021

Cited by 9 | Viewed by 2968

Abstract

We investigated the in vivo effect of curcumin nanoparticles (nC) in addition to diclofenac sodium on local edema and oxidative stress parameters in carrageenan-induced paw edema on rats. Seven groups were investigated: control group (C), the acute inflammation (AI) group, an AI group [...] Read more.

We investigated the in vivo effect of curcumin nanoparticles (nC) in addition to diclofenac sodium on local edema and oxidative stress parameters in carrageenan-induced paw edema on rats. Seven groups were investigated: control group (C), the acute inflammation (AI) group, an AI group treated with Diclofenac (AID, 5 mg/kg b.w. Diclofenac sodium), two AI groups treated with cC (conventional Curcumin)—AIC200 and AIcC200D (D = Diclofenac, 200 represent the concentration of active substance expressed in mg/kg b.w.), and two AI groups with nC (Curcumin nanoparticles)—AIC200 and AIcC200D. Serum and tissue oxidative stress was assessed by measuring five parameters. Curcumin nanoparticles alone and in combination with D better reduced the paw edema than D alone (p < 0.027). The rats treated with D and nC (AIcC200D) had the highest inhibition percentage on edema, reaching the maximum level of inhibition (81%) after 24 h. Conventional curcumin and nC presented antioxidant effects in acute inflammation, with significantly better results obtained for nC. The pro-oxidant markers were reduced up to 0.3 by the cC and up to 0.4 times by the nC and both solutions increased the antioxidant markers up to 0.3 times. The nC enhanced the antioxidative efficacy of D, as this combination reduced the pro-oxidant markers up to 1.3 times. Curcumin nanoparticles could represent a therapeutic option in association with classical nonsteroidal anti-inflammatory medication in acute inflammation, as they might offer a reduction of drug dose and possible limitation of their associated side effects. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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13 pages, 2954 KiB

Open AccessArticle

N-Acetylcysteine in Mechanically Ventilated Rats with Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome: The Effect of Intravenous Dose on Oxidative Damage and Inflammation

by Maros Kolomaznik, Pavol Mikolka, Juliana Hanusrichterova, Petra Kosutova, Katarina Matasova, Jr., Daniela Mokra and Andrea Calkovska

Biomedicines 2021, 9(12), 1885; https://doi.org/10.3390/biomedicines9121885 - 12 Dec 2021

Cited by 6 | Viewed by 2291

Abstract

Treatment of acute respiratory distress syndrome (ARDS) is challenging due to its multifactorial aetiology. The benefit of antioxidant therapy was not consistently demonstrated by previous studies. We evaluated the effect of two different doses of intravenous (i.v.) N-acetylcysteine (NAC) on oxidative stress, [...] Read more.

Treatment of acute respiratory distress syndrome (ARDS) is challenging due to its multifactorial aetiology. The benefit of antioxidant therapy was not consistently demonstrated by previous studies. We evaluated the effect of two different doses of intravenous (i.v.) N-acetylcysteine (NAC) on oxidative stress, inflammation and lung functions in the animal model of severe LPS-induced lung injury requiring mechanical ventilation. Adult Wistar rats with LPS (500 μg/kg; 2.2 mL/kg) were treated with i.v. NAC 10 mg/kg (NAC10) or 20 mg/kg (NAC20). Controls received saline. Lung functions, lung oedema, total white blood cell (WBC) count and neutrophils count in blood and bronchoalveolar lavage fluid, and tissue damage in homogenized lung were evaluated. NAC significantly improved ventilatory parameters and oxygenation, reduced lung oedema, WBC migration and alleviated oxidative stress and inflammation. NAC20 in comparison to NAC10 was more effective in reduction of oxidative damage of lipids and proteins, and inflammation almost to the baseline. In conclusion, LPS-instilled and mechanically ventilated rats may be a suitable model of ARDS to test the treatment effects at organ, systemic, cellular and molecular levels. The results together with literary data support the potential of NAC in ARDS. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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16 pages, 4357 KiB

Open AccessArticle

Effect Mechanism of Electroacupuncture at ST36 on the Injured Extensor Digitorum Longus in the Jumping Rat Model Based on mRNA-Seq Analysis

by Qianqian Liu, Yanwei Guo and Rui Han

Biomedicines 2021, 9(12), 1849; https://doi.org/10.3390/biomedicines9121849 - 07 Dec 2021

Cited by 1 | Viewed by 1917

Abstract

The key target and regulatory mechanism of electroacupuncture of Zusanli (ST36) on extensor longus muscle injury in a jumping rat model were investigated. To this end, 24 female SD rats were randomly divided into the following four groups: no-treatment control group (NON), 6-week [...] Read more.

The key target and regulatory mechanism of electroacupuncture of Zusanli (ST36) on extensor longus muscle injury in a jumping rat model were investigated. To this end, 24 female SD rats were randomly divided into the following four groups: no-treatment control group (NON), 6-week jumping group (J6O), electroacupuncture group after 6-week jumping (J6A), and natural recovery group after 6-week jumping (J6N). After 6 weeks of jumping, in the electroacupuncture group (J6A), electroacupuncture stimulation was applied at Zusanli(ST36) for 20 min per day over the course of 5 days. In the natural recovery group (J6N), rats were fastened with a special apparatus without electroacupuncture stimulation for 20 min at the same time. Transmission electron microscopy, transcriptome sequencing and analysis, Western blotting assay and immunofluorescence staining were performed at the end of our experiment. The recovery effect of J6A rats was more obvious than that of J6N rats and J6O rats as indicated by changes of infiltration of inflammatory cells and morphological structure. Notably, the morphological structure of J6A rats was closer to NON rats in the observation of transmission electron microscopy. CISH/STAT3 regulation was identified by mRNA-seq. The pro-inflammatory response to STAT3 activation was alleviated through up-regulating the expression of CISH protein in J6A rats relative to J6O rats. The level of BAX was decreased and the level of Bcl-2 level was increased in J6A rats relative to J6O rats. Moreover, when compared to J6N rats, the level of Bcl-2 was significantly up-regulated in J6A rats. Increased caspase-3 expression but decreased CDKN2α expression was shown in J6A rats relative to NON rats. These results indicate that the potential mechanism underlying electroacupuncture stimulation of Zusanli (ST36) in repairing the injured extensor digitorum longus following overused jumping may be attributed to CISH/STAT3 regulation of proteins associated with inflammation, apoptosis, and proliferation. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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14 pages, 1675 KiB

Open AccessArticle

Inflammatory, Oxidative Stress, and Apoptosis Effects in Zebrafish Larvae after Rapid Exposure to a Commercial Glyphosate Formulation

by Germano Lanzarin, Carlos Venâncio, Luís M. Félix and Sandra Monteiro

Biomedicines 2021, 9(12), 1784; https://doi.org/10.3390/biomedicines9121784 - 27 Nov 2021

Cited by 22 | Viewed by 3052

Abstract

Glyphosate-based herbicides (GBH) are the most used herbicides in the world, carrying potentially adverse consequences to the environment and non-target species due to their massive and inadequate use. This study aimed to evaluate the effects of acute exposure to a commercial formulation of [...] Read more.

Glyphosate-based herbicides (GBH) are the most used herbicides in the world, carrying potentially adverse consequences to the environment and non-target species due to their massive and inadequate use. This study aimed to evaluate the effects of acute exposure to a commercial formulation of glyphosate, Roundup^® Flex (RF), at environmentally relevant and higher concentrations in zebrafish larvae through the assessment of the inflammatory, oxidative stress and cell death response. Transgenic Tg(mpxGFP)i114 and wild-type (WT) zebrafish larvae (72 h post-fertilisation) were exposed to 1, 5, and 10 µg mL⁻¹ of RF (based on the active ingredient concentration) for 4 h 30 min. A concentration of 2.5 µg mL⁻¹ CuSO₄ was used as a positive control. Copper sulphate exposure showed effectiveness in enhancing the inflammatory profile by increasing the number of neutrophils, nitric oxide (NO) levels, reactive oxygen species (ROS), and cell death. None of the RF concentrations tested showed changes in the number of neutrophils and NO. However, the concentration of 10 µg a.i. mL⁻¹ was able to induce an increase in ROS levels and cell death. The activity of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), the biotransformation activity, the levels of reduced (GSH) and oxidised (GSSG) glutathione, lipid peroxidation (LPO), lactate dehydrogenase (LDH), and acetylcholinesterase (AChE) were similar among groups. Overall, the evidence may suggest toxicological effects are dependent on the concentration of RF, although at concentrations that are not routinely detected in the environment. Additional studies are needed to better understand the underlying molecular mechanisms of this formulation. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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14 pages, 18676 KiB

Open AccessArticle

Secondary Cerebellar Cortex Injury in Albino Male Rats after MCAO: A Histological and Biochemical Study

by Aziza R. Alrafiah

Biomedicines 2021, 9(9), 1267; https://doi.org/10.3390/biomedicines9091267 - 18 Sep 2021

Cited by 4 | Viewed by 3004

Abstract

The present study focused on secondary injury following the middle cerebral artery (MCA) occlusion in rats not linked to the MCA’s feeding zone. This entity has been very rarely studied. Additionally, this study investigated the rates of expression of five fundamental angiogenic biomarkers [...] Read more.

The present study focused on secondary injury following the middle cerebral artery (MCA) occlusion in rats not linked to the MCA’s feeding zone. This entity has been very rarely studied. Additionally, this study investigated the rates of expression of five fundamental angiogenic biomarkers called endoglin, vascular endothelial growth factors-A (VEGF-A), endothelin-1 (ET-1), 2granulocyte colony-stimulating factor (G-CSF), and angiopoietin-using the MCA occlusion (MCAO) model. The random allocation of twelve adult male albino rats was in two groups. As a sham control group, six rats were used. This group was subjected to a sham operation without MCAO. The MCAO group consisted of six rats that were subjected to MCAO operation. After three days, the rats were sacrificed. The cerebellar specimens were immediately processed for light microscopic examination. An angiogenic biomarkers multiplex assay from multiplex was used to assess endoglin levels, VEGF-A, ET-1, angiopoietin-2, and G-CSF in serum samples. Hematoxylin and eosin-stained sections showed that the cerebellar cortex of rats of the MCAO group was more affected than the sham control group. Furthermore, Nissl stain and immunohistochemical analysis revealed an apparent increase in the number of positive immunoreactive in the cerebellar cortex and an evident decrease in Nissl granules in Purkinje cells of the MCAO rats, in contrast to the control rats. In addition, there was a significant increase in angiogenic factors VEGF-A, ET-1, angiopoietin-2, and endoglin. Interestingly, there was an increase in the G-CSF but a non-significant in the MCAO rats compared to the control rats. Furthermore, there was a significant correlation between the angiopoietin-2 and ET-1, and between G-CSF and ET-1. VEGF-A also exhibited significant positive correlations with the G-CSF serum level parameter, Endoglin, and ET-1. Rats subjected to MCAO are a suitable model to study secondary injury away from MCA’s feeding zone. Additionally, valuable insights into the association and interaction between altered angiogenic factors and acute ischemic stroke induced by MCAO in rats. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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Review

Jump to: Research

29 pages, 1515 KiB

Open AccessReview

Antioxidant and Anti-Inflammatory Actions of Polyphenols from Red and White Grape Pomace in Ischemic Heart Diseases

by Ioana Corina Bocsan, Dan Claudiu Măgureanu, Raluca Maria Pop, Antonia Mihaela Levai, Ștefan Octavian Macovei, Ioana Maria Pătrașca, Veronica Sanda Chedea and Anca Dana Buzoianu

Biomedicines 2022, 10(10), 2337; https://doi.org/10.3390/biomedicines10102337 - 20 Sep 2022

Cited by 18 | Viewed by 2950

Abstract

Grape pomace (GP) represents a very reliable source of polyphenols because it could be found globally as a remnant of the wine industry. During the winemaking process, two types of GP are generated: red GP and white GP, according to the produced wine, [...] Read more.

Grape pomace (GP) represents a very reliable source of polyphenols because it could be found globally as a remnant of the wine industry. During the winemaking process, two types of GP are generated: red GP and white GP, according to the produced wine, red or white. Grape pomace represents a viable source of polyphenols, mainly flavanols, procyanidins anthocyanins, and resveratrol which possess antioxidant and anti-inflammatory activities. Multiple differences were observed between red and white GP in terms of their antioxidant and anti-inflammatory activity in both in vitro and in vivo studies. Although most studies are focused on the antioxidant and anti-inflammatory effect of red grape pomace, there are still many variables that need to be taken into consideration, as well as extensive study of the white GP. It was observed that in both in vitro and in vivo studies, the GP polyphenols have a direct antioxidant activity by acting as a free radical scavenger or donating a hydrogen atom. It also possesses an indirect antioxidant and anti-inflammatory activity by reducing mitochondrial reactive oxygen species (ROS) generation, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β), interleukin-6 (IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κβ), and inhibitor of nuclear factor kappa-B kinase subunit beta (Iκκβ) levels or nitrate oxide-4 (NOX4) expression and by increasing the levels of antioxidants enzymes like superoxide dismutase (SOD), catalase (CAT) glutathione reductase (GRx) and glutathione peroxidase(GPx). Besides these activities, many beneficial effects in ischemic heart diseases were also observed, such as the maintenance of the ventricular function as close as possible to normal, and the prevention of infarcted area extension. In this context, this review intends to present the actual knowledge of grape pomace’s potential antioxidant and anti-inflammatory activity in ischemic heart disease, knowledge gathered from existing in vitro and in vivo studies focused on this. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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27 pages, 1359 KiB

Open AccessReview

Modulating the Antioxidant Response for Better Oxidative Stress-Inducing Therapies: How to Take Advantage of Two Sides of the Same Medal?

by Priyanka Shaw, Naresh Kumar, Maxime Sahun, Evelien Smits, Annemie Bogaerts and Angela Privat-Maldonado

Biomedicines 2022, 10(4), 823; https://doi.org/10.3390/biomedicines10040823 - 31 Mar 2022

Cited by 9 | Viewed by 3111

Abstract

Oxidative stress-inducing therapies are characterized as a specific treatment that involves the production of reactive oxygen and nitrogen species (RONS) by external or internal sources. To protect cells against oxidative stress, cells have evolved a strong antioxidant defense system to either prevent RONS [...] Read more.

Oxidative stress-inducing therapies are characterized as a specific treatment that involves the production of reactive oxygen and nitrogen species (RONS) by external or internal sources. To protect cells against oxidative stress, cells have evolved a strong antioxidant defense system to either prevent RONS formation or scavenge them. The maintenance of the redox balance ensures signal transduction, development, cell proliferation, regulation of the mechanisms of cell death, among others. Oxidative stress can beneficially be used to treat several diseases such as neurodegenerative disorders, heart disease, cancer, and other diseases by regulating the antioxidant system. Understanding the mechanisms of various endogenous antioxidant systems can increase the therapeutic efficacy of oxidative stress-based therapies, leading to clinical success in medical treatment. This review deals with the recent novel findings of various cellular endogenous antioxidant responses behind oxidative stress, highlighting their implication in various human diseases, such as ulcers, skin pathologies, oncology, and viral infections such as SARS-CoV-2. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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26 pages, 1585 KiB

Open AccessReview

Oxidative Stress, Inflammation and Connexin Hemichannels in Muscular Dystrophies

by Arlek González-Jamett, Walter Vásquez, Gabriela Cifuentes-Riveros, Rafaela Martínez-Pando, Juan C. Sáez and Ana M. Cárdenas

Biomedicines 2022, 10(2), 507; https://doi.org/10.3390/biomedicines10020507 - 21 Feb 2022

Cited by 5 | Viewed by 3385

Abstract

Muscular dystrophies (MDs) are a heterogeneous group of congenital neuromuscular disorders whose clinical signs include myalgia, skeletal muscle weakness, hypotonia, and atrophy that leads to progressive muscle disability and loss of ambulation. MDs can also affect cardiac and respiratory muscles, impairing life-expectancy. MDs [...] Read more.

Muscular dystrophies (MDs) are a heterogeneous group of congenital neuromuscular disorders whose clinical signs include myalgia, skeletal muscle weakness, hypotonia, and atrophy that leads to progressive muscle disability and loss of ambulation. MDs can also affect cardiac and respiratory muscles, impairing life-expectancy. MDs in clude Duchenne muscular dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy and limb-girdle muscular dystrophy. These and other MDs are caused by mutations in genes that encode proteins responsible for the structure and function of skeletal muscles, such as components of the dystrophin-glycoprotein-complex that connect the sarcomeric-actin with the extracellular matrix, allowing contractile force transmission and providing stability during muscle contraction. Consequently, in dystrophic conditions in which such proteins are affected, muscle integrity is disrupted, leading to local inflammatory responses, oxidative stress, Ca²⁺-dyshomeostasis and muscle degeneration. In this scenario, dysregulation of connexin hemichannels seem to be an early disruptor of the homeostasis that further plays a relevant role in these processes. The interaction between all these elements constitutes a positive feedback loop that contributes to the worsening of the diseases. Thus, we discuss here the interplay between inflammation, oxidative stress and connexin hemichannels in the progression of MDs and their potential as therapeutic targets. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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14 pages, 613 KiB

Open AccessReview

Involvement of Oxidative Stress in the Development of Subcellular Defects and Heart Disease

by Naranjan S. Dhalla, Vijayan Elimban, Monika Bartekova and Adriana Adameova

Biomedicines 2022, 10(2), 393; https://doi.org/10.3390/biomedicines10020393 - 07 Feb 2022

Cited by 16 | Viewed by 2619

Abstract

It is now well known that oxidative stress promotes lipid peroxidation, protein oxidation, activation of proteases, fragmentation of DNA and alteration in gene expression for producing myocardial cell damage, whereas its actions for the induction of fibrosis, necrosis and apoptosis are considered to [...] Read more.

It is now well known that oxidative stress promotes lipid peroxidation, protein oxidation, activation of proteases, fragmentation of DNA and alteration in gene expression for producing myocardial cell damage, whereas its actions for the induction of fibrosis, necrosis and apoptosis are considered to result in the loss of cardiomyocytes in different types of heart disease. The present article is focused on the discussion concerning the generation and implications of oxidative stress from various sources such as defective mitochondrial electron transport and enzymatic reactions mainly due to the activation of NADPH oxidase, nitric oxide synthase and monoamine oxidase in diseased myocardium. Oxidative stress has been reported to promote excessive entry of Ca²⁺ due to increased permeability of the sarcolemmal membrane as well as depressions of Na⁺-K⁺ ATPase and Na⁺-Ca²⁺ exchange systems, which are considered to increase the intracellular of Ca²⁺. In addition, marked changes in the ryanodine receptors and Ca²⁺-pump ATPase have been shown to cause Ca²⁺-release and depress Ca²⁺ accumulation in the sarcoplasmic reticulum as a consequence of oxidative stress. Such alterations in sarcolemma and sarcoplasmic reticulum are considered to cause Ca²⁺-handling abnormalities, which are associated with mitochondrial Ca²⁺-overload and loss of myofibrillar Ca²⁺-sensitivity due to oxidative stress. Information regarding the direct effects of different oxyradicals and oxidants on subcellular organelles has also been outlined to show the mechanisms by which oxidative stress may induce Ca²⁺-handling abnormalities. These observations support the view that oxidative stress plays an important role in the genesis of subcellular defects and cardiac dysfunction in heart disease. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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16 pages, 1363 KiB

Open AccessReview

Oxidative Stress and Antioxidant Nanotherapeutic Approaches for Inflammatory Bowel Disease

by Ping Liu, Yixuan Li, Ran Wang, Fazheng Ren and Xiaoyu Wang

Biomedicines 2022, 10(1), 85; https://doi.org/10.3390/biomedicines10010085 - 31 Dec 2021

Cited by 16 | Viewed by 3185

Abstract

Oxidative stress, caused by the accumulation of reactive species, is associated with the initiation and progress of inflammatory bowel disease (IBD). The investigation of antioxidants to target overexpressed reactive species and modulate oxidant stress pathways becomes an important therapeutic option. Nowadays, antioxidative nanotechnology [...] Read more.

Oxidative stress, caused by the accumulation of reactive species, is associated with the initiation and progress of inflammatory bowel disease (IBD). The investigation of antioxidants to target overexpressed reactive species and modulate oxidant stress pathways becomes an important therapeutic option. Nowadays, antioxidative nanotechnology has emerged as a novel strategy. The nanocarriers have shown many advantages in comparison with conventional antioxidants, owing to their on-site accumulation, stability of antioxidants, and most importantly, intrinsic multiple reactive species scavenging or catalyzing properties. This review concludes an up-to-date summary of IBD nanomedicines according to the classification of the delivered antioxidants. Moreover, the concerns and future perspectives in this study field are also discussed. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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14 pages, 453 KiB

Open AccessReview

Towards Personalized Antioxidant Use in Female Infertility: Need for More Molecular and Clinical Studies

by Jan Tesarik

Biomedicines 2021, 9(12), 1933; https://doi.org/10.3390/biomedicines9121933 - 17 Dec 2021

Cited by 8 | Viewed by 3587

Abstract

Treatment with antioxidants is increasingly used to slow down aging processes in different organs of the human body, including those implicated in female fertility. There is a plethora of different natural, synthetic or semi-synthetic medicines available on the market; most of them can [...] Read more.

Treatment with antioxidants is increasingly used to slow down aging processes in different organs of the human body, including those implicated in female fertility. There is a plethora of different natural, synthetic or semi-synthetic medicines available on the market; most of them can be purchased without medical prescription. Even though the use of antioxidants, even under conditions of auto-medication, was shown to improve many functions related to female infertility related to oxidative stress, the lack of medical control and supervision can lead to an overmedication resulting in an opposite extreme, reductive stress, which can be counterproductive with regard to reproductive function and produce various adverse health effects in general. This paper reviews the current knowledge relative to the effects of different antioxidants on female reproductive function. The persisting gaps in this knowledge are also highlighted, and the need for medical supervision and personalization of antioxidant prescription is underscored. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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14 pages, 556 KiB

Open AccessReview

The Role of Oxidative Stress and Therapeutic Potential of Antioxidants in Graves’ Ophthalmopathy

by Tzu-Yu Hou, Shi-Bei Wu, Hui-Chuan Kau and Chieh-Chih Tsai

Biomedicines 2021, 9(12), 1871; https://doi.org/10.3390/biomedicines9121871 - 10 Dec 2021

Cited by 14 | Viewed by 2785

Abstract

Graves’ ophthalmopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease. It is characterized initially by an inflammatory process, followed by tissue remodeling and fibrosis, leading to proptosis, exposure keratopathy, ocular motility limitation, and compressive optic neuropathy. The pathogenic mechanism is complex [...] Read more.

Graves’ ophthalmopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease. It is characterized initially by an inflammatory process, followed by tissue remodeling and fibrosis, leading to proptosis, exposure keratopathy, ocular motility limitation, and compressive optic neuropathy. The pathogenic mechanism is complex and multifactorial. Accumulating evidence suggests the involvement of oxidative stress in the pathogenesis of GO. Cigarette smoking, a major risk factor for GO, has been shown to induce reactive oxygen species (ROS) generation and oxidative damage in GO orbital fibroblasts. In addition, an elevation in ROS and antioxidant enzymes is observed in tears, blood, and urine, as well as orbital fibroadipose tissues and fibroblasts from GO patients. In vitro and in vivo studies have examined the efficacy of various antioxidant supplements for GO. These findings suggest a therapeutic role of antioxidants in GO patients. This review summarizes the current understanding of oxidative stress in the pathogenesis and potential antioxidants for the treatment of GO. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches 3.0)

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