Protective Effects of Broccoli (Brassica oleracea) against Oxidative Damage in Vitro and in Vivo

In fish, environmental pollution is one factor that induces oxidative stress, and this can disturb the natural antioxidant defense system. Oxidative stress has been well characterized in vitro, yet the in vivo effects of metal-induced oxidative stress have not been extensively studied. In two experiments we examined the impacts of copper (Cu) on gene expression, oxidative damage, and cell oxidative capacity in liver and gill of zebrafish. In the first experiment, soft water-acclimated zebrafish were exposed to 8 and 15 μg/l Cu for 48 h. This exposure resulted in significant increases in gene expression of cytochrome c oxidase subunit 17 (COX-17) and catalase, associated with both increased Cu load and protein carbonyl concentrations in the gill and liver after 48 h. In addition, we examined the potential protective effects of increased waterborne Ca2+(3.3 mM) and Na+(10 mM) on acute Cu toxicity. While both treatments were effective at reducing liver and/or gill Cu loads and attenuating oxidative damage at 48 h, 10 mM Na+was more protective than 3.3 mM Ca2+. There were variable changes in the maximal activities of COX and citrate synthase (CS), indicating possible alterations in cell oxidative capacity. Moreover, Cu affected COX-to-CS ratios in both gill and liver, suggesting that Cu alters normal mitochondrial biogenic processes, possibly though metallochaperones like COX-17. Overall, this study provides important steps in determining the transcriptional and physiological endpoints of acute Cu toxicity in a model tropical species.

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MicroRNA-31-5p Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via Inactivating Cab39/AMPKα Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/8822361 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Wan-li Jiang ◽

Kao-chang Zhao ◽

Wen Yuan ◽

Fang Zhou ◽

Heng-ya Song ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Oxidative Damage ◽

Calcium Binding ◽

Protective Effects ◽

Compound C ◽

Dependent Inhibition ◽

Underlying Mechanisms

Acute lung injury (ALI) and the subsequent acute respiratory distress syndrome remain devastating diseases with high mortality rates and poor prognoses among patients in intensive care units. The present study is aimed at investigating the role and underlying mechanisms of microRNA-31-5p (miR-31-5p) on lipopolysaccharide- (LPS-) induced ALI. Mice were pretreated with miR-31-5p agomir, antagomir, and their negative controls at indicated doses for 3 consecutive days, and then they received a single intratracheal injection of LPS (5 mg/kg) for 12 h to induce ALI. MH-S murine alveolar macrophage cell lines were cultured to further verify the role of miR-31-5p in vitro. For AMP-activated protein kinase α (AMPKα) and calcium-binding protein 39 (Cab39) inhibition, compound C or lentiviral vectors were used in vivo and in vitro. We observed an upregulation of miR-31-5p in lung tissue upon LPS injection. miR-31-5p antagomir alleviated, while miR-31-5p agomir exacerbated LPS-induced inflammation, oxidative damage, and pulmonary dysfunction in vivo and in vitro. Mechanistically, miR-31-5p antagomir activated AMPKα to exert the protective effects that were abrogated by AMPKα inhibition. Further studies revealed that Cab39 was required for AMPKα activation and pulmonary protection by miR-31-5p antagomir. We provide the evidence that endogenous miR-31-5p is a key pathogenic factor for inflammation and oxidative damage during LPS-induced ALI, which is related to Cab39-dependent inhibition of AMPKα.

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Antioxidant Activity, Phenolic Content and Hematoprotective Effects of Cleome arabica Polyphenolic Leaf Extract

Phytothérapie ◽

10.3166/phyto-2019-0206 ◽

2019 ◽

Author(s):

C. Tigrine ◽

A. Kameli

Keyword(s):

Antioxidant Activity ◽

Biological Effects ◽

Reducing Power ◽

Hematological Toxicity ◽

Protective Effects ◽

Ferrous Ions ◽

Polyphenolic Extract ◽

Cleome Arabica

In this study a polyphenolic extract from Cleome arabica leaves (CALE) was investigated for its antioxidant activity in vitro using DPPH•, metal chelating and reducing power methods and for its protective effects against AraC-induced hematological toxicity in vivo using Balb C mice. Results indicated that CALE exhibited a strong and dose-dependent scavenging activity against the DPPH• free radical (IC50 = 4.88 μg/ml) and a high reducing power activity (EC50 = 4.85 μg/ml). Furthermore, it showed a good chelating effects against ferrous ions (IC50 = 377.75 μg/ml). The analysis of blood showed that subcutaneous injection of AraC (50 mg/kg) to mice during three consecutive days caused a significant myelosupression (P < 0.05). The combination of CALE and AraC protected blood cells from a veritable toxicity. Where, the number of the red cells, the amount of hemoglobin and the percentage of the hematocrite were significantly high. On the other hand, AraC cause an elevation of body temperature (39 °C) in mice. However, the temperature of the group treated with CALE and AraC remained normal and did not exceed 37.5 °C. The observed biological effects of CALE, in vitro as well as in vivo, could be due to the high polyphenol and flavonoid contents. In addition, the antioxidant activity of CALE suggested to be responsible for its hematoprotective effect.

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Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

Current Drug Delivery ◽

10.2174/1567201818666201214125237 ◽

2020 ◽

Vol 18 ◽

Author(s):

Zirui Zhang ◽

Shangcong Han ◽

Panpan Liu ◽

Xu Yang ◽

Jing Han ◽

...

Keyword(s):

Wound Healing ◽

Mrna Expression ◽

Tissue Injury ◽

Inflammatory Cells ◽

Pcr Analysis ◽

Protective Effects ◽

Deep Tissue ◽

Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

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Probiotic and Functional Properties of Limosilactobacillus reuteri INIA P572

Nutrients ◽

10.3390/nu13061860 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1860

Author(s):

Patricia Diez-Echave ◽

Izaskun Martín-Cabrejas ◽

José Garrido-Mesa ◽

Susana Langa ◽

Teresa Vezza ◽

...

Keyword(s):

In Vitro Assays ◽

Immunomodulatory Activity ◽

Probiotic Properties ◽

Protective Effects ◽

Mice Model ◽

In Vivo Models ◽

Food Borne ◽

Gastrointestinal Conditions

Limosilactobacillus reuteri INIA P572 is a strain able to produce the antimicrobial compound reuterin in dairy products, exhibiting a protective effect against some food-borne pathogens. In this study, we investigated some probiotic properties of this strain such as resistance to gastrointestinal passage or to colonic conditions, reuterin production in a colonic environment, and immunomodulatory activity, using different in vitro and in vivo models. The results showed a high resistance of this strain to gastrointestinal conditions, as well as capacity to grow and produce reuterin in a human colonic model. Although the in vitro assays using the RAW 264.7 macrophage cell line did not demonstrate direct immunomodulatory properties, the in vivo assays using a Dextran Sulphate Sodium (DSS)-induced colitic mice model showed clear immunomodulatory and protective effects of this strain.

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Protective effects of carbonic anhydrase inhibition in brain ischaemia in vitro and in vivo models

Journal of Enzyme Inhibition and Medicinal Chemistry ◽

10.1080/14756366.2021.1907575 ◽

2021 ◽

Vol 36 (1) ◽

pp. 964-976

Author(s):

Ilaria Dettori ◽

Irene Fusco ◽

Irene Bulli ◽

Lisa Gaviano ◽

Elisabetta Coppi ◽

...

Keyword(s):

Carbonic Anhydrase ◽

Protective Effects ◽

Brain Ischaemia ◽

In Vivo Models ◽

Carbonic Anhydrase Inhibition

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Norepinephrine Protects against Methamphetamine Toxicity through β2-Adrenergic Receptors Promoting LC3 Compartmentalization

International Journal of Molecular Sciences ◽

10.3390/ijms22137232 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7232

Author(s):

Gloria Lazzeri ◽

Carla L. Busceti ◽

Francesca Biagioni ◽

Cinzia Fabrizi ◽

Gabriele Morucci ◽

...

Keyword(s):

Plasma Membrane ◽

Light Chain ◽

Adrenergic Receptors ◽

Cell Damage ◽

Protective Effects ◽

Autophagy Flux ◽

Brain Areas ◽

Indirect Consequence

Norepinephrine (NE) neurons and extracellular NE exert some protective effects against a variety of insults, including methamphetamine (Meth)-induced cell damage. The intimate mechanism of protection remains difficult to be analyzed in vivo. In fact, this may occur directly on target neurons or as the indirect consequence of NE-induced alterations in the activity of trans-synaptic loops. Therefore, to elude neuronal networks, which may contribute to these effects in vivo, the present study investigates whether NE still protects when directly applied to Meth-treated PC12 cells. Meth was selected based on its detrimental effects along various specific brain areas. The study shows that NE directly protects in vitro against Meth-induced cell damage. The present study indicates that such an effect fully depends on the activation of plasma membrane β2-adrenergic receptors (ARs). Evidence indicates that β2-ARs activation restores autophagy, which is impaired by Meth administration. This occurs via restoration of the autophagy flux and, as assessed by ultrastructural morphometry, by preventing the dissipation of microtubule-associated protein 1 light chain 3 (LC3) from autophagy vacuoles to the cytosol, which is produced instead during Meth toxicity. These findings may have an impact in a variety of degenerative conditions characterized by NE deficiency along with autophagy impairment.

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Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

Molecular Medicine ◽

10.1186/s10020-021-00332-0 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Jian-Ping Zhang ◽

Wei-Jing Zhang ◽

Miao Yang ◽

Hua Fang

Keyword(s):

Cell Apoptosis ◽

Ischemia Reperfusion Injury ◽

Glycogen Synthase ◽

Ischemia Reperfusion ◽

Inflammatory Factors ◽

Therapeutic Effects ◽

Protective Effects ◽

Loss Of Function

Abstract Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

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The impact of indole-3-lactic acid on immature intestinal innate immunity and development: a transcriptomic analysis

Scientific Reports ◽

10.1038/s41598-021-87353-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wuyang Huang ◽

Ky Young Cho ◽

Di Meng ◽

W. Allan Walker

Keyword(s):

Lactic Acid ◽

Mechanistic Model ◽

Transcriptomic Analysis ◽

Dependent Manner ◽

Protective Effects ◽

Very Preterm Infants ◽

Anti Inflammatory ◽

The Impact

AbstractAn excessive intestinal inflammatory response may have a role in the pathogenesis of necrotizing enterocolitis (NEC) in very preterm infants. Indole-3-lactic acid (ILA) of breastmilk tryptophan was identified as the anti-inflammatory metabolite involved in probiotic conditioned media from Bifidobacteria longum subsp infantis. This study aimed to explore the molecular endocytic pathways involved in the protective ILA effect against inflammation. H4 cells, Caco-2 cells, C57BL/6 pup and adult mice were used to compare the anti-inflammatory mechanisms between immature and mature enterocytes in vitro and in vivo. The results show that ILA has pleiotropic protective effects on immature enterocytes including anti-inflammatory, anti-viral, and developmental regulatory potentials in a region-dependent and an age-dependent manner. Quantitative transcriptomic analysis revealed a new mechanistic model in which STAT1 pathways play an important role in IL-1β-induced inflammation and ILA has a regulatory effect on STAT1 pathways. These studies were validated by real-time RT-qPCR and STAT1 inhibitor experiments. Different protective reactions of ILA between immature and mature enterocytes indicated that ILA’s effects are developmentally regulated. These findings may be helpful in preventing NEC for premature infants.

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