NF-κB Signaling Pathway In Rats Research Articles

Effect of artemisinin combined with allicin on improving cardiac function, fibrosis and NF-κB signaling pathway in rats with diabetic cardiomyopathy

Myocardial fibrosis and inflammation cause cardiac hypertrophy, arrhythmias, and heart failure in diabetics, a leading cause of mortality. Since it’s complicated, no drug treats diabetic cardiomyopathy. This research examined the effects of artemisinin and allicin on heart function, myocardial fibrosis, and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway in diabetic cardiomyopathy rats. A total of 50 rats were separated into 5 groups, 10 of which were the control group. 40 rats received 65 μg/g streptozotocin intraperitoneally. 37 of 40 animals fit the investigation. The artemisinin, allicin, and artemisinin/allicin groups each included nine animals. The artemisinin group received 75 mg/kg of artemisinin, the allicin group received 40 mg/kg of allicin, and the combination group received equal dosages of artemisinin and allicin gavage for four weeks. After the intervention, in each group cardiac functions, myocardial fibrosis, and NF-κB signaling pathway protein expression were assessed. All of the examined groups had greater levels of LVEDD, LVESD, LVEF, FS, E/A, and the NF-κB pathway proteins: NF-κB p65 and p-NF-κB p65 than the normal group, except for the combination group. Artemisinin and allicin did not vary statistically. Compared to the model group, the artemisinin, allicin, and combined groups showed various degrees of improvement from the pathological pattern, with more intact muscle fibers, neater arrangement, more normal cell morphology, artemisinin and allicin alleviated cardiac dysfunction and decreased myocardium fibrosis in diabetic cardiomyopathy rats by inactivating the NF-κB signaling cascade.

Sulfasalazine Inhibits Inflammation and Fibrogenesis in Pancreas via NF-κB Signaling Pathway in Rats with Oxidative Stress-Induced Pancreatic Injury [Retraction

[This retracts the article DOI: 10.2147/DDDT.S107679.].

Rhein Inhibits NF-κB Signaling Pathway to Alleviate Inflammatory Response and Oxidative Stress of Rats with Chronic Glomerulonephritis.

Objective To explore the effect and mechanism of rhein on chronic glomerulonephritis (CGN). Method Twenty-four eight-week-old male SD rats were randomly divided into following 4 groups (6 rats in each group): control group, CGN group, rhein group, and benazepril (Ben) group. And 5 mg/mL of cationization-bovine serum albumin (C-BSA) was mixed with an equal volume of Freund's incomplete adjuvant for the preparation of 2.5 mg/mL of C-BSA solution. The rat model of CGN was established by injection of C-BSA for six weeks. Calculation of the renal index in rats was conducted. Biochemical detection was performed to measure the level of 24 h urinary protein, blood urea nitrogen (BUN), serum creatinine (SCr), and serum albumin (ALB) of the rats, as well as the level of malondiadehyde (MDA), superoxide (SOD), and glutathione peroxidase (GSH-Px) in the kidney tissue. Hematoxylin and eosin (H&E) staining was utilized to measure histological changes in the kidney of the rats. The level of TNF-α, IL-1β, IL-6, and ICAM-1 in rat kidney tissues was determined by enzyme-linked immunosorbent assay (ELISA). Western blot was applied to check the expression of NF-κB in the nucleus and cytoplasm as well as the expression of IκBα and p-IκBα in rat kidney tissues. Results Rhein could decline urinary protein, restore blood biochemical parameters, and protect renal tissue in rats with CGN. Besides, rhein could inhibit the activity of the NF-κB signaling pathway in rats with CGN and could alleviate the inflammatory response and oxidative stress level at the same time. Conclusion Rhein alleviates inflammatory responses and oxidative stress in rats with CGN. It also provides a theoretical basis and data support for the therapeutic drugs for CGN.

Astragalus polysaccharide inhibits apoptosis and inflammation to alleviate chronic atrophic gastritis through NF-κB signaling pathway in rats

Chronic atrophic gastritis (CAG) is a process of inflammation characterized by injured gastric mucosal epithelium leading to reduction of mucosal glands, often accompanied by intestinal or pseudopyloric metaplasia. Astragalus polysaccharide (APS) is reported to improve gastric mucosal damage and inflammation, but its role in CAG remains elusive. Therefore, we intended to analyze the impact of APS on CAG and its potential mechanism to provide novel insight into the treatment for the disorder. After establishment of CAG model using MNNG method, the rats were administered Vitazyme (200 mg/kg), or low, moderate and high concentration of APS (20, 40, 60 mg/kg), respectively, with healthy rats as controls and some CAG rats untreated. After that, the rat gastric tissues were pathologically examined and ELISA, Western blot analysis and staining were carried out to assess the impact of treatment on inflammation and apoptosis Pathologically, APS treatment alleviated the pathological changes of CAG rats, reducing inflammatory cell infiltration and inflammation. Besides, APS significantly diminished the content of pro-inflammatory factors and decreased the level of gastrointestinal hormones. In the presence of APS, the apoptosis of gastric mucosal cells was inhibited and the p-NF-κB p65 and p-IKKα/β expression was decreased. Collectively, APS could mitigate inflammation and gastric mucosal damage in CAG, as it also suppresses the process of apoptosis and inactivates the NF-κB signaling pathway. In a word, APS treatment improves CAG via NF-κB pathway.

Retraction: A20 rescues hepatocytes from apoptosis through the NF-κB signaling pathway in rats with acute liver failure.

This article is being retracted from Bioscience Reports at the request of the authors following receipt of a notification from a reader, alerting the Editorial Office to the data in Figures 5A and 5C as well as the Western blots in Figures 1C and 6B.The Editorial Office contacted the authors to request the raw data and raw images of the Western blots, to which the authors responded with the Retraction request stating that the integrity of the research was damaged. Given the concerns raised the Editor-in-Chief and Editorial Board agree with the Retraction. The co-corresponding author Huang-Shan wishes to take full responsibility for their negligence, and apologizes for the inconvenience caused to the journal and readers.

Retraction: A20 rescues hepatocytes from apoptosis through the NF-κB signaling pathway in rats with acute liver failure

Retraction: A20 rescues hepatocytes from apoptosis through the NF-κB signaling pathway in rats with acute liver failure

Grape seed extract ameliorates PhIP-induced colonic injury by modulating gut microbiota, lipid metabolism, and NF-κB signaling pathway in rats

Abstract 2-Amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) is a common carcinogen produced in thermally processed protein-rich foods. This study explored the protective effects of grape seed extract (GSE) against colonic injury induced by short-term exposure to PhIP and the underlying mechanisms involved. Wistar rats were randomly divided into four groups: control, GSE only (GSE), PhIP (PhIP), and GSE prevention (GPhIP). In the GPhIP group, rats were fed a diet supplemented with GSE for 2 weeks before administering PhIP. GSE significantly ameliorated PhIP-induced oxidative stress and colonic DNA damage. Moreover, GSE effectively maintained homeostasis in intestinal flora, especially by preventing PhIP-mediated reduction in Lactobacillus abundance. Fecal metabolome and colonic transcriptome analyses revealed that GSE remarkably ameliorated PhIP-induced colonic injury by regulating lipid metabolic pathways. Notably, nuclear factor-κB signaling pathway involved in the process of prevention. Therefore, GSE is recommended as an effective dietary supplement to prevent the harm of PhIP in vivo.

A20 rescues hepatocytes from apoptosis through the NF-κB signaling pathway in rats with acute liver failure.

Background: Acute liver failure (ALF) is a disease of acute derangements in the hepatic synthetic function with defects involving innate immune responses, which was reported to be negatively regulated by tumor necrosis factor α-induced protein 3 (A20). Herein, the present study was conducted to investigate the effects the A20 protein on the proliferation and apoptosis of hepatocytes through the nuclear factor (NF)-κB signaling pathway in the rat models simulating ALF.Methods: Male Wistar rats were used to simulate ALF in the model rats. Next, the positive expression of A20 and Caspase-3 proteins was measured in liver tissues. Rat hepatocytes were separated and subjected to pyrrolidine dithiocarbamate (PDTC, inhibitor of NF-κB pathway) or A20 siRNA. Additionally, both mRNA and protein levels of A20, NF-κB, tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), and receptor-interacting protein 1 (RIP1) were determined. Finally, we detected the hepatocyte proliferation, cell cycle entry, and apoptosis.Results: ALF rats displayed a lower positive expression of A20 protein and a higher expression of Caspase-3 protein. Furthermore, A20 was down-regulated, while NF-κB, TRAF6, and RIP1 were all up-regulated in ALF rats. Notably, A20 inhibited activation of NF-κB signaling pathway. The blockade of NF-κB signaling pathway enhanced proliferation and cell cycle progression of hepatocytes, whereas inhibited apoptosis of hepatocytes. On the contrary, A20 siRNA reversed the above situation.Conclusion: A20 inhibits apoptosis of hepatocytes and promotes the proliferation through the NF-κB signaling pathway in ALF rats, potentially providing new insight into the treatment of ALF.

Regulatory effect of emodin on NF-κB signaling pathway in rats with acute liver failure

Regulatory effect of emodin on NF-κB signaling pathway in rats with acute liver failure

Erratum to: Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-κB Signaling Pathway in Rats.

Erratum to: Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-κB Signaling Pathway in Rats.

Nano NiO induced liver toxicity via activating the NF-κB signaling pathway in rats.

Studies have demonstrated that nano NiO could induce liver toxicity in rats, but its mechanism remains unclear. This study aimed to explore the role of the NF-κB signaling pathway in rat liver toxicity after nano NiO exposure. Male Wistar rats were exposed to nano NiO (0.015, 0.06 and 0.24 mg per kg b.w.) and micro NiO (0.24 mg per kg b.w.) by intratracheal instillation twice a week for 6 weeks. To investigate the liver toxicity induced by nano NiO, the indicators of liver function and inflammatory response were detected, and the histopathological changes were observed. The levels of NF-κB signaling pathway related gene and protein expression were examined using RT-qPCR and western blot techniques in the liver tissue. The results showed that the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyltranspeptidase (GGT) increased after nano NiO exposure. Cellular edema, hepatic sinus disappearance, and neutrophil and lymphocyte infiltration were observed. Nano NiO increased the concentrations of pro-inflammatory cytokines (IL-1β and IL-6), but decreased the levels of anti-inflammatory cytokines (IL-4 and IL-10). It also induced the upregulation of TNF-α, NF-κB-inducible kinase (NIK), IκB kinase alpha (IKK-α) and NF-κB mRNA, while inducing the downregulation of the inhibitor kappa B (IκB) alpha. In addition, we found that the protein content of NIK, IKK-α, p-IKK-α, p-IκB-α and NF-κB was elevated, whereas that of IκB-α was reduced. The results indicated that the NF-κB signaling pathway played an important role in rat liver toxicity induced by nano NiO.

Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-κB Signaling Pathway in Rats.

Acute lung injury (ALI), a common component of systemic inflammatory disease, is a life-threatening condition without many effective treatments. Fisetin, a natural flavonoid from fruits and vegetables, was reported to have wide pharmacological properties such as anti-inflammatory, antioxidant, and anticancer activities. The aim of this study was to detect the effects of fisetin on lipopolysaccharide (LPS)-induced acute lung injury and investigate the potential mechanism. Fisetin was injected (1, 2, and 4mg/kg, i.v.) 30min before LPS administration (5mg/kg, i.v.). Our results showed that fisetin effectively reduced the inflammatory cytokine release and total protein in bronchoalveolar lavage fluids (BALF), decreased the lung wet/dry ratios, and obviously improved the pulmonary histology in LPS-induced ALI. Furthermore, fisetin inhibited LPS-induced increases of neutrophils and macrophage infiltration and attenuated MPO activity in lung tissues. Additionally, fisetin could significantly inhibit the Toll-like receptor 4 (TLR4) expression and the activation of NF-κB in lung tissues. Our data indicates that fisetin has a protective effect against LPS-induced ALI via suppression of TLR4-mediated NF-κB signaling pathways, and fisetin may be a promising candidate for LPS-induced ALI treatment.

Effects of hydrogen-rich saline on early diabetic neuropathic pain in rats

Objective To evaluate the effects of hydrogen-rich saline on the early diabetic neuropathic pain (DPN) in rats.Methods Healthy male Sprague-Dawley rats,aged 8 weeks,weighing 180-220 g,were used in the study.DPN model was made by intraperitoneal injection of 1％ streptozocin (STZ) 65 mg/kg.Twelve diabetic rats were randomly divided into 2 groups (n =6 each) using a random number table:DPN group and hydrogen-rich saline group (HRS group).Another 6 normal rats were randomly collected as control group (group C).At 14 days after STZ injection,hydrogen-rich saline 5 ml/kg was injected intraperitoneally once a day for 14 consecutive days in HRS group,while C and DNP groups received the equal volume of normal saline.Mechanical paw withdrawal threshold to yon Frey stimuli (MWT) and paw withdrawal latency to nociceptive thermal stimulation (TWL) were measured at 2 days before STZ injection (To) and 7,14,21 and 28 days after STZ injection (T1-4).The motor nerve conduction velocity (MNCV) of the right hindlimb and distal motor latency was measured after pain threshold was measured at T4.After measurement of neurological function was completed,tumor necrosis factor-α (TNF-α) and i nterleukin-6 (IL-6) contents (by ELISA) and nuclear factor kappa B (NF-κB) activity (by immuno-histochemistry) were detected.Results Compared with group C,MNCV was significantly decreased,the motor latency was prolonged,MWT was decreased at T1-T4,TWL was shortened at T2-T4,TNF-a and IL-6 contents were increased,and NF-κB activity was enhanced in DNP and HRS groups (P ＜ 0.05).Compared with group DNP,MNCV was significandy increased,the motor latency was shortened,MWT was increased at T3.4,TWL was prolonged at T4,TNF-a and IL-6 contents were decreased,and NF-κB activity was weakened in group HRS (P ＜ 0.05).Conclusion Hydrogen-rich saline can relieve the early DPN through inhibiting NF-κB signaling pathway in rats. Key words: Hydrogen; Diabetes mellitus; Neuralgia

Berberine ameliorates chronic kidney injury caused by atherosclerotic renovascular disease through the suppression of NFκB signaling pathway in rats.

Background and objectivesImpaired renal function in atherosclerotic renovascular disease (ARD) may be the result of crosstalk between atherosclerotic renovascular stenosis and amplified oxidative stress, inflammation and fibrosis. Berberine (BBR) regulates cholesterol metabolism and exerts antioxidant effects. Accordingly, we hypothesized that BBR treatment may ameliorate ARD-induced kidney injury through its cholesterol-lowering effect and also suppression of the pathways involved in oxidative stress, inflammation and NFκB activation.MethodsMale rats were subjected to unilateral renal artery stenosis with silver-irritant coil, and then fed with 12-week hypercholesterolemic diet. Rats with renal artery stenosis were randomly assigned to two groups (n = 6 each) – ARD, or ARD+BBR – according to diet alone or in combination with BBR. Similarly, age-matched rats underwent sham operation and were also fed with hypercholesterolemic diet alone or in combination with BBR as two corresponding controls. Single-kidney hemodynamic metrics were measured in vivo with Doppler ultrasound to determine renal artery flow. The metrics reflecting hyperlipidemia, oxidative stress, renal structure and function, inflammation and NFκB activation were measured, respectively.ResultsCompared with control rats, ARD rats had a significant increase in urinary albumin, plasma cholesterol, LDL and thiobarbituric acid reactive substances (TBARS) and a significant decrease in SOD activity. When exposed to 12-week BBR, ARD rats had significantly lower levels in blood pressure, LDL, urinary albumin, and TBARS. In addition, there were significantly lower expression levels of iNOS and TGF-β in the ARD+BBR group than in the ARD group, with attenuated NFκB-DNA binding activity and down-regulated protein levels of subunits p65 and p50 as well as IKKβ.ConclusionsWe conclude that BBR can improve hypercholesterolemia and redox status in the kidney, eventually ameliorating chronic renal injury in rats with ARD, and that BBR can act against proinflammatory and profibrotic responses through suppression of the NFκB signaling pathway.

Effect of exogenous hydrogen sulfide on myocardial NF-κB signaling pathway in rats with hemorrhagic shock

Objective To investigate the effect of exogenous hydrogen sulfide on myocardial NF-kB sig- naling pathway in rats with hemorrhagic shock （HS） .Methods Forty adult male rats, weighing 250-300 g, were randomly divided into 4 groups （ n = 10 each） ： sham operation group （Sham group）, sham operation ＋ NariS group （Sham ＋ NariS group）, HS group and HS ＋ NariS group. HS was induced by withdrawing blood from the femoral artery. After HS, NariS 28 μmol/kg was injected intraperitoneally at 10 min before resuscitation in groups HS ＋ NariS and Sham ＋ NariS. MAP was monitored and recorded at 0, 1.5, 2, 3, 4 and 6 h after blood-letting. The rats were then sacrificed and hearts were removed for determination of phosphorylated IKKβ （pIKKβ）, IkBa （pIkBa）, NF-kB p65 （pNF-kB p65） and high-mobility group box 1 （HMGB1） and for examination of myocardial ultrastructure with light arid electron microscope. Results Compared with Sham and Sham ＋ NaSH groups, MAP was significantly decreased and the expression of pIKKβ, pIkBa, pNF-kB p65 and HMGB1 was up-regulated in HS and HS ＋ Naris groups （ P 〈 0.05）. Compared with HS group, MAP was significantly increased and the expres- sion of pIKKβ, pIkBa, pNF-kB p65 and HMGB1 was down-regulated in HS ＋ NariS group （P 〈 0.05）. The pathologic changes were attenuated in HS ＋ NariS group compared with group HS. Conclusion Exogenous hydro- gen sulfide can attenuate myocardial injury induced by HS through inhibition of NF-kB signaling pathway and re- duction of inflammatory response. Key words: Hydrogen sulfide; Shock,hemorrhagic; Myocardial reperfusion injury; NF-kappa B