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

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.

scholarly journals Daphnetin Attenuated Cisplatin-Induced Acute Nephrotoxicity With Enhancing Antitumor Activity of Cisplatin by Upregulating SIRT1/SIRT6-Nrf2 Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Xiaoye Fan ◽  
Wei Wei ◽  
Jingbo Huang ◽  
Liping Peng ◽  
Xinxin Ci
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Cell Damage ◽  
Protective Effects ◽  
Normal Tissues ◽  
Nrf2 Signaling Pathway ◽  
Apoptosis Pathways ◽  
Underlying Mechanisms

Cisplatin (CDDP) is a widely used drug for cancer treatment that exhibits major side effects in normal tissues, such as nephrotoxicity in kidneys. The Nrf2 signaling pathway, a regulator of mitochondrial dysfunction, oxidative stress and inflammation, is a potential therapeutic target in CDDP-induced nephrotoxicity. We explored the underlying mechanisms in wild-type (WT) and Nrf2−/− mice on CDDP-induced renal dysfunction in vivo. We found that Nrf2 deficiency aggravated CDDP-induced nephrotoxicity, and Daph treatment significantly ameliorated the renal injury characterized by biochemical markers in WT mice and reduced the CDDP-induced cell damage. In terms of the mechanism, Daph upregulated the SIRT1 and SIRT6 expression in vivo and in vitro. Furthermore, Daph inhibited the expression level of NOX4, whereas it activated Nrf2 translocation and antioxidant enzymes HO-1 and NQO1, and alleviated oxidative stress and mitochondrial dysfunction. Moreover, Daph suppressed CDDP-induced NF-κB and MAPK inflammation pathways, as well as p53 and cleaved caspase-3 apoptosis pathways. Notably, the protective effects of Daph in WT mice were completely abrogated in Nrf2−/− mice. Moreover, Daph enhanced, rather than attenuated, the tumoricidal effect of CDDP.

scholarly journals Schizandrin Protects against OGD/R-Induced Neuronal Injury by Suppressing Autophagy: Involvement of the AMPK/mTOR Pathway

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3624 ◽  
Author(s):  
Guangyun Wang ◽  
Tiezheng Wang ◽  
Yuanyuan Zhang ◽  
Fang Li ◽  
Boyang Yu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Pc12 Cells ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Mtor Pathway ◽  
Protective Effects ◽  
Compound C

The neuroprotective role of schizandrin (SA) in cerebral ischemia-reperfusion (I/R) was recently highlighted. However, whether SA plays a regulatory role on autophagy in cerebral I/R injury is still unclear. This study aimed to explore whether the neuroprotective mechanisms of SA were linked to its regulation of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/autophagy pathway in vivo and in vitro. The present study confirmed that SA significantly improved oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced PC12 cells injury. The results of immunoblotting and confocal microscope showed that SA decreased autophagy in OGD/R-injured PC12 cells, which was reflected by the decreased Beclin-1 and LC3-II expression, autophagy flux level, and LC3 puncta formation. In addition, the autophagy inducer rapamycin partially prevented the effects of SA on cell viability and autophagy after OGD/R, whereas the autophagy inhibitor 3-methyladenine (3-MA) exerted the opposite effect. The results of Western blotting showed that SA markedly decreased the phosphorylation of AMPK (p-AMPK), whereas the phosphor-mTOR (p-mTOR) levels increased in the presence of OGD/R insult. Furthermore, pretreatment with the AMPK inducer AICAR partially reversed the protective effects and autophagy inhibition of SA. However, AMPK inhibitor Compound C pretreatment further promoted the inhibition of SA on autophagy induction and cell damage induced by OGD/R. Taken together, these findings demonstrate that SA protects against OGD/R insult by inhibiting autophagy through the regulation of the AMPK-mTOR pathway and that SA may have therapeutic value for protecting neurons from cerebral ischemia.

scholarly journals A REVIEW ON POTENTIAL PROPERTIES AND THERAPEUTIC APPLICATIONS OF LYCOPENE

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Bharat Kwatra
Keyword(s):  
Animal Studies ◽  
Inflammatory Responses ◽  
Cell Damage ◽  
Antioxidant Properties ◽  
Epidemiological Studies ◽  
Protective Effects ◽  
Beneficial Role

The present review is based mainly on papers published between 2000 and 2011 and gives information about the properties of the carotenoid lycopene in chemical and biological systems and its possible role in preventing cardiovascular diseases (CVD). The main aim of this report is to highlight its role as an antioxidant, also reported are bioactive properties that may influence the development of foam cells and protection against endothelial cell damage. The paper will also examine recent observations that lycopene may improve blood flow and reduce inflammatory responses. Lycopene possesses antioxidant properties in vitro, and some epidemiological studies have reported protective effects against the progression of CVD. The oxidation of human low density lipoproteins (LDL) is a fundamental mechanism in the initiation of atherosclerosis. A beneficial role of lycopene as antioxidant in the prevention of CVD is suggested but the data are still controversial. Lycopene is believed to be the most potent carotenoid antioxidant in vitro. Tissue culture experiments and animal studies support potential cardioprotective effects for lycopene and other carotenoids in the blood. Most studies showed beneficial effects of lycopene to individuals who are antioxidant-deficient like elderly patients, or humans exposed to higher levels of oxidative stress like smokers, diabetics, hemodialysis patients and acute myocardial infarction patients. By defining the right population and combining antioxidant potentials of lycopene with vitamins and other bioactive plant compounds, the beneficial role of lycopene in CVD can be clarified in future studies. Keywords: Atherosclerosis, isomerization, in vitro, in vivo, LDL oxidatin

scholarly journals Montelukast Protects Against Renal Damage Due to Cadmium Toxicity: In vivo and In vitro Experiments

2021 ◽  
Vol 15 (4) ◽  
pp. 223-232
Author(s):  
Farnoosh Kaviani ◽  
◽  
Missagh Jalali ◽  
Elham Hoveizi ◽  
Javad Jamshidian ◽  
...  
Keyword(s):  
Vitamin E ◽  
Cell Damage ◽  
Cadmium Toxicity ◽  
Antioxidant Properties ◽  
Protective Effects ◽  
Human Embryonic Kidney Cells ◽  
Pre Treatment ◽  
Gpx Activity

Background: The protective effects of Montelukast (Mont), as an anti-inflammatory drug, against cadmium-induced kidney cell damage have already been studied and identified. Since the significant part of cadmium nephrotoxicity is caused by oxidative stress, this in vivo and in vitro study was conducted to investigate the possible role of Montelukast antioxidant properties in the protection. Methods: In the in vivo section, 42 rats were treated in seven groups of six rats as follows: Control; Cadmium Chloride (CdCl2) control; Montelukast control; CdCl2 plus Montelukast treatment; CdCl2 with Montelukast pre-treatment; Vitamin E control; CdCl2 plus Vitamin E treatment. In the in vitro section, human embryonic kidney cells (HEK293) were treated with CdCl2; Montelukast; Combined CdCl2 and Montelukast; Vitamin E; Combined CdCl2 and Vitamin E. Results: Montelukast, in both treatment and pretreatment forms, reduced serum urea, creatinine, and potassium levels compared to CdCl2 group, in vivo. Similar to vitamin E, the pre-treatment with Montelukast was associated with a significant decrease in Nitric Oxide (NO) and Total Antioxidant Capacity (TAC) in serum and renal tissue, and a significant increase in Glutathione Peroxidase (GPX) activity in serum compared those in the CdCl2 group. In the in vitro section of the study, Montelukast significantly reduced Malondialdehyde (MDA) and NO while the TAC level, Superoxide Dismutase (SOD), and the GPX activity increased significantly. Conclusion: Overall, the antioxidant effects of Montelukast appear to play a prominent role in preventing the renal toxicity due to cadmium exposure.

Protective Effect of Boswellic Resin Against Memory Loss and Alzheimer’s Induced by Aluminum Tetrachloride and D-Galactose (Experimental study in Mice)

2020 ◽  
Author(s):  
K. Zerrouki ◽  
N. Djebli ◽  
L. Gadouche ◽  
I. Erdogan Orhan ◽  
F. SezerSenol Deniz ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Protective Effect ◽  
Cell Damage ◽  
Memory Loss ◽  
Control Group ◽  
Total Extract ◽  
Swiss Mice ◽  
Octyl Acetate

Nowadays, because of the industrialization, a lot of contaminant were available ; the consequences of this availability are apparition of diseases including neurodegeneration. Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. This study is based on the effect of the Boswellic resin, which is from a medicinal plant and known for its antioxidant effects on nerve cell damage. The objective of this work was to evaluate the in vitro and in vivo effects of the Boswellic resin on anticholinesterase activity and Alzheimer’s disease (AD) induced by D-galactose and aluminum tetrachloride in Swiss mice. Chemical composition of the resin essential oil was identified by the CG-MS analysis. The antioxidant activity was also assessed by the DMPD and metal chelation methods. In order to understand the mechanism of memory improvement, the acetylcholinesterase, AChE, and butyrylcholinesterase, BChE, inhibitory assays were performed. In vivo part of the study was achieved on Swiss mice divided into four groups: control, AD model, treated AD, and treated control group. The identification of chemical composition by CG-MS reach the 89.67% of the total extract compounds presented some very important molecules (p-Cymene, n-Octyl acetate, α-Pinene…). The present study proves that Boswellic resin improves memory and learning in treated Alzheimer’s group, modulates the oxidative stress and be involved in the protective effect against amyloid deposition and neurodegeneration, and stimulates the immune system in mice’s brain.

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

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.

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

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.

scholarly journals RNF141 interacts with KRAS to promote colorectal cancer progression

Oncogene ◽  
2021 ◽  
Author(s):  
Jiuna Zhang ◽  
Xiaoyu Jiang ◽  
Jie Yin ◽  
Shiying Dou ◽  
Xiaoli Xie ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Plasma Membrane ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Critical Role ◽  
Ring Finger ◽  
Immunohistochemical Analysis ◽  
Bimolecular Fluorescence Complementation

AbstractRING finger proteins (RNFs) play a critical role in cancer initiation and progression. RNF141 is a member of RNFs family; however, its clinical significance, roles, and mechanism in colorectal cancer (CRC) remain poorly understood. Here, we examined the expression of RNF141 in 64 pairs of CRC and adjacent normal tissues by real-time PCR, Western blot, and immunohistochemical analysis. We found that there was more expression of RNF141 in CRC tissue compared with its adjacent normal tissue and high RNF141 expression associated with T stage. In vivo and in vitro functional experiments were conducted and revealed the oncogenic role of RNF141 in CRC. RNF141 knockdown suppressed proliferation, arrested the cell cycle in the G1 phase, inhibited migration, invasion and HUVEC tube formation but promoted apoptosis, whereas RNF141 overexpression exerted the opposite effects in CRC cells. The subcutaneous xenograft models showed that RNF141 knockdown reduced tumor growth, but its overexpression promoted tumor growth. Mechanistically, liquid chromatography-tandem mass spectrometry indicated RNF141 interacted with KRAS, which was confirmed by Co-immunoprecipitation, Immunofluorescence assay. Further analysis with bimolecular fluorescence complementation (BiFC) and Glutathione-S-transferase (GST) pull-down assays showed that RNF141 could directly bind to KRAS. Importantly, the upregulation of RNF141 increased GTP-bound KRAS, but its knockdown resulted in a reduction accordingly. Next, we demonstrated that RNF141 induced KRAS activation via increasing its enrichment on the plasma membrane not altering total KRAS expression, which was facilitated by the interaction with LYPLA1. Moreover, KRAS silencing partially abolished the effect of RNF141 on cell proliferation and apoptosis. In addition, our findings presented that RNF141 functioned as an oncogene by upregulating KRAS activity in a manner of promoting KRAS enrichment on the plasma membrane in CRC.

scholarly journals Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3005
Author(s):  
Kanchan Bhardwaj ◽  
Ana Sanches Silva ◽  
Maria Atanassova ◽  
Rohit Sharma ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Experimental Data ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Fungal Infections ◽  
Cell Damage ◽  
Cancer Growth ◽  
Naturally Occurring ◽  
Antioxidant Effects

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.

scholarly journals Probiotic and Functional Properties of Limosilactobacillus reuteri INIA P572

Nutrients ◽  
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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