scholarly journals 5-LIPOXYGENASE INHIBITOR (ZILEUTON) PRODUCES ANTI-DEPRESSION EFFECT IN STRESS INDUCE CRS MICE MODEL

2019 ◽  
pp. 154-162
Author(s):  
SAPTARSHI PANIGRAHI ◽  
SOMNATH SURAI ◽  
HAO HONG
Keyword(s):  
Caspase 3 ◽  
Molecular Level ◽  
Behavioral Tests ◽  
Mice Model ◽  
Lipoxygenase Inhibitor ◽  
Treatment Groups ◽  
Tnf Α ◽  
Crs Model

Objective: The experiment aimed to find out the effectiveness of Zileuton, a 5-LOX inhibitor on depressive behavior and neuroinflammation in vivo. Method: Male ICR mice (25-30g) randomly distributed Veh+Veh, CRS+Vehicle, CRS+ZIL50, and CRS+ZIL100. Zileuton was orally given in the treatment groups for 21 days after 3 weeks of stress induce CRS model. Starting from the day 1, in CRS model, mice were immobilized 8 hr/day for consecutive 21 days to induce stress. After completing the drug administration, subjected the mice for behavioral tests, and then performed histopathological & Western Blotting. Result: Stress induces CRS model guide to the significant depressive-like behavior of the mice in behavioral tests which was united by adverse changes at the cellular/molecular level responsible for regulation of inflammatory and apoptotic processes. CRS triggered Microglial over activation in the DG of the hippocampus, which was successfully inhibited by Zileuton post-treatment at the dose of 100mg/kg than 50mg/kg. Level of TNF-α, IL- 1β, nuclear NF-κB p65, Bax, and cleaved Caspase-3 was high and Bcl-2 expression was low in the stress induce CRS -treated mice which were found to be opposite in the Zileuton (100mg/kg). However, the dose of 50mg/kg less to mimic the effects as exhibited more by the 100mg/kg dose of Zileuton. Conclusion: It can be concluded that selective 5-lipoxygenase inhibitor Zileuton can efficiently inhibit the depressive-like behavior/activity in CRS-induced depressive mouse model. The study is the first to show the role of 5-lipoxygenase enzyme in and Chronic Restraint Stress (CRS)-induced mice models of stress, anxiety or depression.

Platelet Aggregation in Whole Blood: The Role of Thromboxane A2 and Adenosine Diphosphate

1985 ◽  
Vol 54 (03) ◽  
pp. 612-616 ◽  
Author(s):  
A J Carter ◽  
S Heptinstall
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Adenosine Diphosphate ◽  
Blood Platelet ◽  
Thromboxane B2 ◽  
Lipoxygenase Inhibitor ◽  
Thromboxane Synthase Inhibitor ◽  
Synthase Inhibitor

SummaryThe platelet aggregation that occurred in whole blood in response to several aggregating agents (collagen, arachidonic acid, adenosine diphosphate, adrenaline and thrombin) was measured using an Ultra-Flo 100 Whole Blood Platelet Counter. The amounts of thromboxane B2 produced were measured by radioimmunoassay. The effects of various inhibitors of thromboxane synthesis and the effects of apyrase, an enzyme that destroys adenosine diphosphate, were determined.Platelet aggregation was always accompanied by the production of thromboxane B2, and the amounts produced depended on the nature and concentration of the aggregating agent used. The various inhibitors of thromboxane synthesis - aspirin and flurbiprofen (cyclo-oxygenase inhibitors), BW755C (a cyclo-oxygenase and lipoxygenase inhibitor) and dazoxiben (a selective thromboxane synthase inhibitor) - did not markedly inhibit aggregation. Results obtained using apyrase showed that adenosine diphosphate contributed to the aggregation process, and that its role must be acknowledged when devising means of inhibiting platelet aggregation in vivo.

Ursodeoxycholic acid abrogates gentamicin-induced hepatotoxicity in rats: Role of NF-κB-p65/TNF-α, Bax/Bcl-xl/Caspase-3, and eNOS/iNOS pathways

Life Sciences ◽  
2020 ◽  
Vol 254 ◽  
pp. 117760 ◽  
Author(s):  
Fares E.M. Ali ◽  
Emad H.M. Hassanein ◽  
Adel G. Bakr ◽  
Ehab A.M. El-Shoura ◽  
Dalia A. El-Gamal ◽  
...  
Keyword(s):  
Ursodeoxycholic Acid ◽  
Caspase 3 ◽  
Tnf Α

scholarly journals Halofuginone functions as a therapeutic drug for chronic periodontitis in a mouse model

2020 ◽  
Vol 34 ◽  
pp. 205873842097489
Author(s):  
Jiang Wang ◽  
Bo Wang ◽  
Xin Lv ◽  
Yingjie Wang
Keyword(s):  
Alveolar Bone ◽  
Immune Cell ◽  
Critical Role ◽  
Therapeutic Drug ◽  
Mice Model ◽  
T Helper 17 ◽  
Th17 Cell Differentiation ◽  
Tnf Α

Periodontitis is an inflammatory disease caused by host immune response, resulting in a loss of periodontium and alveolar bone. Immune cells, such as T cells and macrophages, play a critical role in the periodontitis onset. Halofuginone, a natural quinazolinone alkaloid, has been shown to possess anti-fibrosis, anti-cancer, and immunomodulatory properties. However, the effect of halofuginone on periodontitis has never been reported. In this study, a ligature-induced mice model of periodontitis was applied to investigate the potential beneficial effect of halofuginone on periodontitis. We demonstrated that the administration of halofuginone significantly reduced the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in vivo, and markedly suppressed immune cell infiltration into the infected sites. Furthermore, we also observed that halofuginone treatment blocked the T-helper 17 (Th17) cell differentiation in vivo and in vitro. We demonstrated for the first time that halofuginone alleviated the onset of periodontitis through reducing immune responses.

scholarly journals Subinhibitory Antimicrobial Concentrations: A Review of In Vitro and In Vivo Data

1992 ◽  
Vol 3 (4) ◽  
pp. 193-201 ◽  
Author(s):  
George G Zhanel ◽  
Daryl J Hoban ◽  
Godfrey KM Harding
Keyword(s):  
Antimicrobial Activity ◽  
Animal Studies ◽  
Molecular Level ◽  
Bacterial Virulence ◽  
Antibacterial Effects ◽  
Wide Range ◽  
Immune Defences

Antimicrobial activity is not an ‘all or none’ effect. An increase in the rate and extent of antimicrobial action is usually observed over a wide range of antimicrobial concentrations. Subinhibitory antimicrobial concentrations are well known to produce significant antibacterial effects, and various antimicrobials at subinhibitory concentrations have been reported to inhibit the rate of bacterial growth. Bacterial virulence may be increased or decreased by subinhibitory antimicrobial concentrations by changes in the ability of bacteria to adhere to epithelial cells or by alterations in bacterial susceptibility to host immune defences. Animal studies performed in rats, hamsters and rabbits demonstrate decreased bacterial adherence, reduced infectivity and increased survival of animals treated with subinhibitory antimicrobial concentrations compared to untreated controls. The major future role of investigation of subinhibitory antimicrobial concentrations will be to define more fully, at a molecular level, how antimicrobials exert their antibacterial effects.

3-methyadenine inhibits lipopolysaccharides-induced pulmonary inflammation at the early stage of silicosis via blocking NF-κB signaling pathway

2021 ◽  
pp. 074823372110394
Author(s):  
Yujing Zhang ◽  
Shuai Huang ◽  
Shiyi Tan ◽  
Mingke Chen ◽  
Shang Yang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Late Stage ◽  
Caspase 3 ◽  
Inflammatory Responses ◽  
Early Stage ◽  
Pulmonary Inflammation ◽  
Mechanism Study ◽  
Silica Dust ◽  
Tnf Α

Occupational exposure to silica dust is related to pulmonary inflammation and silicosis. Lipopolysaccharides (LPSs) could aggravate apoptosis in alveolar macrophages (AMs) of human silicosis through autophagy, yet how the reduction of autophagy attenuated LPS-induced lung injury and the related mechanisms need to be investigated. In the study, we aim to understand the role of 3-methyladenine (3-MA), an inhibitor of autophagy, in LPS-mediated inflammatory responses and fibrosis. We collected AMs from observers/silicosis patients. The results showed that LPS induced NF-κB-related pulmonary inflammation in observers and silicosis patients, as confirmed by an increase in the expression of IL-1β, IL-6, TNF-α, and p65, which could be inhibited by 3-MA treatment. In mice models, at the early stage (7d) of silicosis, but not the late (28d) stage, blocking autophagy reversed the increased levels of IL-1β, IL-6, TNF-α, and p65 caused by LPS. Mechanism study revealed that LPS triggered the expression of LC3 II, p62, and cleaved caspase-3 at the early stage exposed to silica, which could be restored by 3-MA, while there was no difference in the expression of LAMP1 either at the early or late stage of silicosis in different groups. Similarly, 3-MA treatment did not prevent fibrosis characterized by destroyed alveoli, collagen deposition, and increased expression of α-SMA and Col-1 induced by LPS at the late stage of silicosis. The results suggested that 3-MA has a role in the protection of lung injury at the early stage of silicosis and provided an experimental basis for preventive strategies of pulmonary inflammation and silicosis.

scholarly journals Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 325 ◽  
Author(s):  
Xiaojuan Li ◽  
Yunping Tang ◽  
Fangmiao Yu ◽  
Yu Sun ◽  
Fangfang Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Nude Mouse Model ◽  
Dose Dependent

We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future.

scholarly journals Effectiveness of Vitamin C and Vitamin E Antioxidant Combination on Caspase-3 Expression in Wistar White Rat Pulmonum Contusion

2020 ◽  
Vol 3 (1) ◽  
pp. 31-44
Author(s):  
Bermansyah ◽  
Gama Satria ◽  
Ahmad Umar
Keyword(s):  
Cell Death ◽  
Vitamin E ◽  
Vitamin C ◽  
Wistar Rats ◽  
Caspase 3 ◽  
Cell Function ◽  
Pulmonary Contusion ◽  
Tnf Α ◽  
Male Wistar Rats

Introduction.Pulmonary contusions can cause a progressive inflammatory response. Activation of TNF-α cytokines and reactive oxygen species (ROS) can cause pulmonary cell death. Antioxidants can have the potential to neutralize ROS. The purpose of this study is to determine the effectiveness of antioxidant administration in maintaining pulmonary cell function in wistar rats that have been induced to experience pulmonary contusions through caspase-3 levels. Methods.This study was an in vivo experimental study conducted on thirty male wistar rats and divided into five groups (n = 6): control, pulmonary contusion + asthaxanthine 5 mg/kgBW, pulmonary contusion + vitamin C and E 50 mg/kgBW, pulmonary contusion + vitamin C and E 100 mg/kgBW, pulmonary contusion + vitamin C and E 200 mg/kgBW. The value of Caspase-3 is evaluated by the IHC. All data analyzes used SPSS 18. Results. Low doses of antioxidants have the potential to reduce pulmonary cell death in wistar rats induced by pulmonary contusions.Conclussion. Vitamin C and E effective to reduce polmonary cell death in pulmonary contusion.Keywords: antioxidants, vitamin C, vitamin E, pulmonary contusions animal model, apoptosis, caspase-3

scholarly journals MiR-22-3p suppresses sepsis-induced acute kidney injury by targeting PTEN

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xudong Wang ◽  
Yali Wang ◽  
Mingjian Kong ◽  
Jianping Yang
Keyword(s):  
Acute Kidney Injury ◽  
Inflammatory Response ◽  
Periodic Acid ◽  
Kidney Injury ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Tnf Α

Abstract Background: Septic acute kidney injury is considered as a severe and frequent complication that occurs during sepsis. The present study was performed to understand the role of miR-22-3p and its underlying mechanism in sepsis-induced acute kidney injury. Methods: Rats were injected with adenovirus carrying miR-22-3p or miR-NC in the caudal vein before cecal ligation. Meanwhile, HK-2 cells were transfected with the above adenovirus following LPS stimulation. We measured the markers of renal injury (blood urea nitrogen (BUN), serum creatinine (SCR)). Histological changes in kidney tissues were examined by hematoxylin and eosin (H&E), Masson staining, periodic acid Schiff staining and TUNEL staining. The levels of IL-1β, IL-6, TNF-α and NO were determined by ELISA assay. Using TargetScan prediction and luciferase reporter assay, we predicted and validated the association between PTEN and miR-22-3p. Results: Our data showed that miR-22-3p was significantly down-regulated in a rat model of sepsis-induced acute kidney injury, in vivo and LPS-induced sepsis model in HK-2 cells, in vitro. Overexpression of miR-22-3p remarkably suppressed the inflammatory response and apoptosis via down-regulating HMGB1, p-p65, TLR4 and pro-inflammatory factors (IL-1β, IL-6, TNF-α and NO), both in vivo and in vitro. Moreover, PTEN was identified as a target of miR-22-3p. Furthermore, PTEN knockdown augmented, while overexpression reversed the suppressive role of miR-22-3p in LPS-induced inflammatory response. Conclusions: Our results showed that miR-22-3p induced protective role in sepsis-induced acute kidney injury may rely on the repression of PTEN.

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