scholarly journals The Potential Toxicity of Silver Nanoparticles After Repeated Oral Exposure and Underlying Mechanisms in Kidney of Rat Model

2021 ◽  
Author(s):  
Hamed Nosrati ◽  
Manijeh Hamzepoor ◽  
Maryam Sohrabi ◽  
Massoud Saidijam ◽  
Mohammad Javad Assari ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Critical Role ◽  
Oral Exposure ◽  
Rt Pcr ◽  
Histological Changes ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Pas Staining ◽  
Underlying Mechanisms

Abstract Background: Silver nanoparticles (AgNPs) can accumulate in various organs after orally exposure. This study evaluated the toxicity of AgNPs in vivo on histological changes, apoptosis and expression of growth factor genes in kidney. Methods: The male Wistar rats were treated orally with 30,125,300, and 700 mg/kg silver nanoparticles solution. After 28 days of exposure, histopatological changes were assessed by hematoxylin-eosin, trichrome Masson, and Pas staining. Apoptosis was quantified by TUNEL and immunohistochemistry of caspase-3, and level of expression of growth factors mRNAs were determined using RT-PCR. Results: Histopathologic examination revealed degenerative changes in the glomeruli, loss of tubular architecture, loss of brush border and interrupted tubular basal laminae. These changes were more noticeable in 30, and 125 mg/kg groups. The collagen intensity was increased in 30 treated groups in both cortex and medulla. Apoptosis was much more evident in middle dose groups (125 and 300 mg/kg). The results of RT-PCR indicated that Bcl-2 and Bax mRNAs upregulated in treated groups (p<0.05) and data of the EGF, TNF-α, and TGF-β1 revealed that AgNPs induced more enormous changes in gene expression in 30 and 700 mg/kg groups compared to control. Conclusion: Our observations showed that the AgNPs played a critical role in their in vivo renal toxicity.

scholarly journals The potential renal toxicity of silver nanoparticles after repeated oral exposure and its underlying mechanisms

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hamed Nosrati ◽  
Manijeh Hamzepoor ◽  
Maryam Sohrabi ◽  
Massoud Saidijam ◽  
Mohammad Javad Assari ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Molecular Mechanisms ◽  
Renal Toxicity ◽  
Periodic Acid ◽  
Critical Role ◽  
Oral Exposure ◽  
Control Group ◽  
Rt Pcr ◽  
Periodic Acid Schiff

Abstract Background Silver nanoparticles (AgNPs) can accumulate in various organs after oral exposure. The main objective of the current study is to evaluate the renal toxicity induced by AgNPs after repeated oral exposure and to determine the relevant molecular mechanisms. Methods In this study, 40 male Wistar rats were treated with solutions containing 30, 125, 300, and 700 mg/kg of AgNPs. After 28 days of exposure, histopathological changes were assessed using hematoxylin-eosin (H&E), Masson’s trichrome, and periodic acid-Schiff (PAS) staining. Apoptosis was quantified by TUNEL and immunohistochemistry of caspase-3, and the level of expression of the mRNAs of growth factors was determined using RT-PCR. Results Histopathologic examination revealed degenerative changes in the glomeruli, loss of tubular architecture, loss of brush border, and interrupted tubular basal laminae. These changes were more noticeable in groups treated with 30 and 125 mg/kg. The collagen intensity increased in the group treated with 30 mg/kg in both the cortex and the medulla. Apoptosis was much more evident in middle-dose groups (i.e., 125 and 300 mg/kg). The results of RT-PCR indicated that Bcl-2 and Bax mRNAs upregulated in the treated groups (p < 0.05). Moreover, the data related to EGF, TNF-α, and TGF-β1 revealed that AgNPs induced significant changes in gene expression in the groups treated with 30 and 700 mg/kg compared to the control group. Conclusion Our observations showed that AgNPs played a critical role in in vivo renal toxicity.

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 A critical role of the T3SS effector EseJ in intracellular trafficking and replication ofEdwardsiella piscicidain non-phagocytic cells

2018 ◽  
Author(s):  
Lingzhi Zhang ◽  
Jiatiao Jiang ◽  
Tianjian Hu ◽  
Jin Zhang ◽  
Xiaohong Liu ◽  
...  
Keyword(s):  
Bacterial Colonization ◽  
Critical Role ◽  
Host Cells ◽  
Intracellular Replication ◽  
Phagocytic Cells ◽  
T3ss Effector ◽  
Early Endosomes ◽  
Underlying Mechanisms ◽  
Endosome Maturation

AbstractEdwardsiella piscicida(E. piscicida) is an intracellular pathogen within a broad spectrum of hosts. Essential toE. piscicidavirulence is its ability to survive and replicate inside host cells, yet the underlying mechanisms and the nature of the replicative compartment remain unclear. Here, we characterized its intracellular lifestyle in non-phagocytic cells and showed that intracellular replication ofE. piscicidain non-phagocytic cells is dependent on its type III secretion system. Following internalization,E. piscicidais contained in vacuoles that transiently mature into early endosomes, but subsequently bypasses the classical endosome pathway and fusion with lysosomes which depends on its T3SS. Following a rapid escape from the degradative pathway,E. piscicidawas found to create a specialized replication-permissive niche characterized by endoplasmic reticulum (ER) markers. We also found that a T3SS effector EseJ is responsible for intracellular replication ofE. piscicidaby preventing endosome/lysosome fusion. Furthermore,in vivoexperiments confirmed that EseJ is necessary for bacterial colonization ofE. piscicidain both mice and zebrafish. Thus, this work elucidates the strategies used byE. piscicidato survive and proliferate within host non-phagocytic cells.Author summaryE. piscicidais a facultative intracellular bacterium associated with septicemia and fatal infections in many animals, including fish and humans. However, little is known about its intracellular life, which is important for successful invasion of the host. The present study is the first comprehensive characterization ofE. piscicida’s intracellular life-style in host cells. Upon internalization,E. piscicidais transiently contained in Rab5-positive vacuoles, but the pathogen prevents further endosome maturation and fusion with lysosomes by utilizing an T3SS effector EseJ. In addition, the bacterium creates an specialized replication niche for rapid growth via an interaction with the ER. Our study provides new insights into the strategies used byE. piscicidato successfully establishes an intracellular lifestyle that contributes to its survival and dissemination during infection.

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 In Vivo Antioxidant And Kidney Protective Potential Of Atorvastatin In Rat Cadmium-Induced Toxicity

2021 ◽  
Author(s):  
Esmaeil Karami ◽  
Zahra Goodarzi ◽  
Ali Ghanbari ◽  
Ahmad Reza Bandegi ◽  
Sedighe Yosefi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Biochemical Parameters ◽  
Cadmium Chloride ◽  
Rat Kidney ◽  
Intraperitoneal Administration ◽  
Kidney Injury ◽  
Protective Role ◽  
Histological Changes ◽  
Male Wistar Rats

Abstract Purpose: Environmental and occupational exposure to cadmium chloride is known to cause nephrotoxicity linked with oxidative stress in humans and animals. This study used Atorvastatin to examine its effect on cadmium chloride-induced nephrotoxicity in rat model using biochemical and histological methodologies.Methods: Experiments were performed on 56 adult male Wistar rats (200 ±20 g), randomly assigned to eight groups. Atorvastatin was administered by oral for 15 days at 20 mg/kg/day, started 7 days before cadmium chloride intraperitoneal administration (1, 2, and 3 mg/kg) for eight days. On day 16, blood samples were collected, and kidneys were excised to evaluate the biochemical and histopathological changes.Cadmium chloride significantly increased malondialdehyde (MDA), serum creatinine (Cr), blood urea nitrogen (BUN), and decreased superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GPx) levels. Results: Administration of Atorvastatin (20 mg/kg) significantly improved lipid peroxidation, glutathione and activities of antioxidant enzymes and significantly decreased BUN and Creatinine. Atorvastatin clearly improved the histological changes, demonstrating its protective role against Cadmium chloride-induced kidney injury.Conclusion: Treatment with Atorvastatin significantly improves all biochemical parameters and suggests a protecting role against cadmium chloride-induced oxidative stress and histological changes in rat kidney.

Shen-Fu Attenuates Endotoxin-Induced Acute Lung Injury in Rats

2006 ◽  
Vol 34 (04) ◽  
pp. 613-621 ◽  
Author(s):  
Yanning Qian ◽  
Jie Sun ◽  
Zhongyun Wang ◽  
Jianjun Yang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Inflammation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Nf Kappa B ◽  
Lung Weight ◽  
Tnf Α ◽  
Male Wistar Rats

Sepsis is associated with the highest risk of progression to acute lung injury or acute respiratory distress syndrome. Shen-Fu has been advocated to treat many severely ill patients. Our study was designed to investigate the effect of Shen-Fu on endotoxin-induced acute lung injury in vivo. Adult male Wistar rats were randomly divided into 6 groups: controls; those challenged with endotoxin (5 mg/kg) and treated with saline; those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (1 mg/kg); those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (10 mg/kg); increase challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (100 mg/kg); saline injected and treated with Shen-Fu (100 mg/kg). TNF-α, IL-6, and NF-kappa B were investigated in the lung two hours later. Myeloperoxidase (MPO) activity and wet/dry weight ratio were investigated six hours later. Intravenous administration of endotoxin provoked significant lung injury, which was characterized by increment increase of MPO activity and wet/dry lung weight ratio, and TNF-α and IL-6 expression and NF-kappa B activation. Shen-Fu (10,100 mg/kg) decreased MPO activity and wet/dry weight ratio and inhibited TNF-α and IL-6 production, endotoxin-induced NF-kappa B activation. Our results indicated that Shen-Fu at a dose of higher than 10 mg/kg inhibited endotoxin-induced pulmonary inflammation in vivo.

A novel fluorinated stilbene exerts hepatoprotective properties in CCl4-induced acute liver damage

2011 ◽  
Vol 89 (10) ◽  
pp. 759-766 ◽  
Author(s):  
Horacio Rivera ◽  
Martha S. Morales-Ríos ◽  
Wendy Bautista ◽  
Mineko Shibayama ◽  
Víctor Tsutsumi ◽  
...  
Keyword(s):  
Liver Damage ◽  
Inflammatory Responses ◽  
Acute Liver Damage ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Glutamyl Transpeptidase

There has been a recently increase in the development of novel stilbene-based compounds with in vitro anti-inflamatory properties. For this study, we synthesized and evaluated the anti-inflammatory properties of 2 fluorinated stilbenes on carbon tetrachloride (CCl4)-induced acute liver damage. To achieve this, CCl4 (4 g·kg–1, per os) was administered to male Wistar rats, followed by either 2-fluoro-4′-methoxystilbene (FME) or 2,3-difluoro-4′-methoxystilbene (DFME) (10 mg·kg–1, per os). We found that although both of the latter compounds prevented cholestatic damage (γ-glutamyl transpeptidase activity), only DFME showed partial but consistent results in the prevention of necrosis, as assessed by both alanine aminotransferase activity and histological analysis. Since inflammatory responses are mediated by cytokines, mainly tumour necrosis factor α (TNF-α), we used the Western blot technique to determine the action of FME and DFME on the expression level of this cytokine. The observed increase in the level of TNF-α caused by CCl4 administration was only prevented by treatment with DFME, in agreement with our biochemical findings. This result was confirmed by measuring interleukin-6 (IL-6) levels, since the expression of this protein depends on the level of TNF-α. In this case, DFME completely blocked the CCl4-induced increase of IL-6. Our results suggest that DFME possesses greater anti-inflammatory properties in vivo than FME. DFME constitutes a possible therapeutic agent for liver disease and could serve as a template for structure optimization.

scholarly journals Dachengqi Decoction Attenuates Intestinal Vascular Endothelial Injury in Severe Acute Pancreatitis in Vitro and in Vivo

2017 ◽  
Vol 44 (6) ◽  
pp. 2395-2406 ◽  
Author(s):  
Li-yun Pan ◽  
Ya-feng Chen ◽  
Hong-chang Li ◽  
Li-ming Bi ◽  
Wen-jie Sun ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Serum Amylase ◽  
Endothelial Damage ◽  
Intestinal Injury ◽  
Control Group ◽  
Rt Pcr ◽  
Intestinal Tissue ◽  
Tnf Α

Background/Aims: Dachengqi decoction (DCQD) is a well-known traditional Chinese herbal drug with strong anti-inflammatory effects. Angiopoietin-1 (Ang-1) plays a vital role in maintaining the stability and integrity of the vascular wall and prevents vascular leakage due to inflammatory mediators. Our previous work found that DCQD protects against pancreatic injury in rats with severe acute pancreatitis (SAP). This study aims to investigate the effects of DCQD on intestinal endothelial damage in both damaged human umbilical vein endothelial cells (HUVECs) and SAP rats. Methods: HUVECs were randomly divided into four groups: control group, TNF-α group, TNF-α plus Ang-1 group (Ang-1 group), and TNF-α plus DCQD group (DCQD group). Cells were incubated for 6 h, 12 h, and 24 h, before collection. The treatment concentration of DCQD was decided based on a Cell Counting Kit-8 (CCK-8) assay. The monolayer permeability of the HUVECs was assessed by measuring the transendothelial electrical resistance (TEER). Apoptosis was analyzed by flow cytometry. mRNA and protein expression of aquaporin 1 (AQP-1), matrix metalloproteinase 9 (MMP9), and junctional adhesion molecule-C (JAM-C) was evaluated by RT-PCR, immunocytofluorescence, and western blot. Forty male Sprague-Dawley rats were randomized into a control group, SAP group, SAP plus Ang-1 group (Ang-1 group), and SAP plus DCQD group (DCQD group). SAP was induced by intraperitoneal injection of cerulein and lipopolysaccharide (LPS), while the control group received 0.9% saline solution. Evans blue was injected through the penile vein and the rats were then sacrificed 12 h after modeling. Levels of serum amylase, TNF-α, IL-1β, IL-2, and IL-6 were determined by using ELISA. Intestinal tissue was analysed by histology, and capillary permeability in the tissues was evaluated by Evans blue extravasation assay. Protein and mRNA expression of AQP-1, MMP9, and JAM-C were assessed by immunohistofluorescence, western blot, and RT-PCR. Results: DCQD reduced the permeability of HUVEC induced by TNF-α in vitro. Furthermore, DCQD altered the mRNA and protein levels of JAM-C, MMP9, and AQP-1 in HUVECs after TNF-α induction. SAP intestinal injury induced by cerulein combined with lipopolysaccharides was concomitant with increased expression of JAM-C and MMP9, and reduced expression of AQP-1 in intestinal tissue. Pretreatment with DCQD attenuated SAP intestinal injury and lowered the levels of serum amylase, TNF–α, IL-1β, IL-2, and IL-6 effectively. Our study demonstrated that DCQD decreased the expression of JAM-C and MMP9 and increased the expression of AQP-1 both in vitro and in vivo. Conclusion: DCQD can reduce capillary endothelial damage in acute pancreatitis-associated intestinal injury and the mechanism may be associated with the regulation of endothelial barrier function-associated proteins AQP-1, MMP9, and JAM-C.

scholarly journals Molecular Mechanism of MiR-136-5p Targeting NF-κB/A20 in the IL-17-Mediated Inflammatory Response after Spinal Cord Injury

2017 ◽  
Vol 44 (3) ◽  
pp. 1224-1241 ◽  
Author(s):  
Jichen He ◽  
Jinmin Zhao ◽  
Xiaoming Peng ◽  
Xiongzhi Shi ◽  
Shaohui Zong ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Factors ◽  
Scoring Method ◽  
Histological Changes ◽  
Cord Injury ◽  
Rat Astrocytes ◽  
Underlying Mechanisms

Background/Aims: The pathophysiology of spinal cord injury (SCI) results in serious damage to the human body via an increase in the secondary biological processes imposed by activated astrocytes. Abnormal expression of microRNAs after SCI has become a potential research focus. However, the underlying mechanisms are poorly understood. Methods: SCI models were established in rats using Allen’s method, and the BBB scoring method was employed to assess locomotor function. Lentivirus was used to infect rat astrocytes and SCI rats. Real-time PCR and antibody chip were used to measure gene expression and cytokine secretion. Western blot analysis was employed to detect protein expression. HE staining was used to assess the histological changes in SCI. The immunohistochemical staining of A20 and p-NF-κB in SCI was also analyzed. Results: The in vitro experiment showed that miR-136-5p up-regulated the expression of p-NF-κB by down-regulating the expression of A20 so that astrocytes produced inflammatory factors and chemokines. The in vivo experiment indicated that overexpressed miR-136-5p promoted the production of inflammatory factors, chemokines and p-NF-κB in SCI rats, whereas it inhibited the expression of A20 protein and increased inflammatory cell infiltration and injuries in the spinal cord. Conclusion: The current findings indicate that silencing miR-136-5p effectively decreased inflammatory factors and chemokines and protected the spinal cord via NF-κB/A20 signaling in vivo and in vitro. In contrast, overexpression of miR-136-5p had the opposite effect.

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