Necroptosis is a key pathogenic event in human and experimental murine models of non-alcoholic steatohepatitis

2015 ◽  
Vol 129 (8) ◽  
pp. 721-739 ◽  
Author(s):  
Marta B. Afonso ◽  
Pedro M. Rodrigues ◽  
Tânia Carvalho ◽  
Marta Caridade ◽  
Paula Borralho ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatic Steatosis ◽  
Murine Models ◽  
Alcoholic Steatohepatitis ◽  
Regulated Necrosis ◽  
Tnf Α ◽  
And Oxidative Stress

Focusing on regulated necrosis in the liver, this study demonstrates that necroptosis contributes to NAFLD pathogenesis in humans and in experimental murine models of hepatic steatosis and NASH. Further, it establishes the involvement of TNF-α and oxidative stress in necroptotic signalling in hepatocytes.

scholarly journals Are N-acetylcysteine and adalimumab effective for non-alcoholic steatohepatitis?

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Mustafa Yalçın ◽  
Muhammed Ali Kıyak ◽  
Mesut Akarsu ◽  
Aslı Çelik ◽  
Göksel Bengi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Treatment Options ◽  
Diet Group ◽  
Normal Diet ◽  
The Other ◽  
Albino Rats ◽  
Necrosis Factor Alpha ◽  
Alcoholic Steatohepatitis ◽  
Tnf Α ◽  
And Oxidative Stress

Due to the lack of effective medical treatment for non-alcoholic steatohepatitis (NASH), we aimed to evaluate new treatment options. In particular, our goal was to investigate and compare the effects of N-acetylcysteine (NAC) and Adalimumab treatment on tumor necrosis factor alpha (TNF-α) and oxidative stress during the development of NASH in a rat model of the disease. Our study included a total of 35 female Wistar albino rats that were divided into 5 groups of 7 each, and evaluated over a 6 week period. One group received a normal diet, while the other four groups received a methionine and choline deficient (MCD) diet. One of the groups receiving the MCD diet did not take any medicine, while the other three were administered NAC, adalimumab, or a NAC/adalimumab combination therapy. NASH was successfully established in the MCD diet group. Levels of TNF-α were effectively suppressed in the three groups that received therapy. Even though adalimumab significantly enhanced suppression of TNF-α, the NASH score was suppressed to a more statistically significant extent in the groups receiving NAC. Our study showed that TNF-α and oxidative stress play an important role in NASH pathogenesis. The antioxidant agent, NAC, was found to be superior to the anti-TNF agent, Adalimumab, in the improvement of total NASH score. Although these drugs did not prevent the development of NASH, it was shown that they mildly reverse the NASH histopathology score, suggesting improvement of and overall liver function.

Inhibition of microRNA-155 Alleviates Neurological Dysfunction Following Transient Global Ischemia and Contribution of Neuroinflammation and Oxidative Stress in the Hippocampus

2020 ◽  
Vol 25 (40) ◽  
pp. 4310-4317 ◽  
Author(s):  
Lichao Sun ◽  
Shouqin Ji ◽  
Jihong Xing
Keyword(s):  
Oxidative Stress ◽  
Brain Edema ◽  
Severity Score ◽  
Global Ischemia ◽  
Signal Pathways ◽  
Neurological Severity Score ◽  
Tnf Α ◽  
Transient Global Ischemia ◽  
And Oxidative Stress

Background/Aims: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. Methods: CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. Results: We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. Conclusion: We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.

Febuxostat Attenuates the Progression of Periodontitis in Rats

Pharmacology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Naseratun Nessa ◽  
Miyuki Kobara ◽  
Hiroe Toba ◽  
Tetsuya Adachi ◽  
Toshiro Yamamoto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Bone Resorption ◽  
Alveolar Bone ◽  
Alveolar Bone Loss ◽  
Gingival Tissue ◽  
Systemic Effects ◽  
Rt Pcr ◽  
Tnf Α ◽  
And Oxidative Stress

Introduction: Periodontitis is a lifestyle-related disease that is characterized by chronic inflammation in gingival tissue. Febuxostat, a xanthine oxidase inhibitor, exerts anti-inflammatory and antioxidant effects. Objective: The present study investigated the effects of febuxostat on periodontitis in a rat model. Methods: Male Wistar rats were divided into 3 groups: control, periodontitis, and febuxostat-treated periodontitis groups. Periodontitis was induced by placing a ligature wire around the 2nd maxillary molar and the administration of febuxostat (5 mg/kg/day) was then initiated. After 4 weeks, alveolar bone loss was assessed by micro-computed tomography and methylene blue staining. The expression of osteoprotegerin (OPG), a bone resorption inhibitor, was detected by quantitative RT-PCR and immunological staining, and the number of osteoclasts in gingival tissue was assessed by tartrate-resistant acid phosphatase staining. The mRNA and protein expression levels of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), in gingival tissue were measured using quantitative RT-PCR and immunological staining. Oxidative stress in gingival tissue was evaluated by the expression of 4-hydroxy-2-nonenal (4-HNE), and 8-hydroxy-2-deoxyguanosine (8-OHdG). To clarify the systemic effects of periodontitis, blood pressure and glucose tolerance were examined. Results: In rats with periodontitis, alveolar bone resorption was associated with reductions in OPG and increases in osteoclast numbers. The gingival expression of TNF-α, IL-1β, 4-HNE, and 8-OHdG was up-regulated in rats with periodontitis. Febuxostat significantly reduced alveolar bone loss, proinflammatory cytokine levels, and oxidative stress. It also attenuated periodontitis-induced glucose intolerance and blood pressure elevations. Conclusion: Febuxostat prevented the progression of periodontitis and associated systemic effects by inhibiting proinflammatory mediators and oxidative stress.

scholarly journals Targeting ROS/NF-κB sigaling pathway by the seedless black Vitis vinifera polyphenols in CCl4-intoxicated kidney, lung, brain, and spleen in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Noha H. Habashy ◽  
Ahmad S. Kodous ◽  
Marwa M. Abu-Serie
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Vitis Vinifera ◽  
Rat Kidney ◽  
Environmental Pollutant ◽  
Enhancing Effect ◽  
Tnf Α ◽  
Cox 2 ◽  
Histopathological Studies ◽  
And Oxidative Stress

AbstractCarbon tetrachloride (CCl4) is an abundant environmental pollutant that can generate free radicals and induce oxidative stress in different human and animal organs like the kidney, lung, brain, and spleen, causing toxicity. The present study evaluated the alleviative mechanism of the isolated polyphenolic fraction from seedless (pulp and skin) black Vitis vinifera (VVPF) on systemic oxidative and necroinflammatory stress in CCl4-intoxicated rats. Here, we found that the administration of VVPF to CCl4-intoxicated rats for ten days was obviously ameliorated the CCl4-induced systemic elevation in ROS, NO and TBARS levels, as well as MPO activity. Also, it upregulated the cellular activities of the enzymatic (SOD, and GPx) and non-enzymatic (TAC and GSH) antioxidants. Furthermore, the gene expression of the ROS-related necroinflammatory mediators (NF-κB, iNOS, COX-2, and TNF-α) in the kidney, brain, and spleen, as well as IL-1β, and IL-8 in the lung were greatly restored. The histopathological studies confirmed these biochemical results and showed a noticeable enhancing effect in the architecture of the studied organs after VVPF intake. Thus, this study indicated that VVPF had an alleviative effect on CCl4-induced necroinflammation and oxidative stress in rat kidney, lung, brain, and spleen via controlling the ROS/NF-κB pathway.

II. Cytochrome P-450 enzymes and oxidative stress

2001 ◽  
Vol 281 (5) ◽  
pp. G1135-G1139 ◽  
Author(s):  
Graham Robertson ◽  
Isabelle Leclercq ◽  
Geoffrey C. Farrell
Keyword(s):  
Oxidative Stress ◽  
Fatty Acid ◽  
Molecular Oxygen ◽  
Hepatic Steatosis ◽  
Nonalcoholic Steatohepatitis ◽  
Acid Oxidation ◽  
Cellular Injury ◽  
Second Hit ◽  
Cytochrome P 450 ◽  
And Oxidative Stress

Oxidative stress is present in the liver of humans with steatosis and nonalcoholic steatohepatitis (NASH) and is a plausible mediator of cellular injury, inflammatory recruitment, and fibrogenesis. CYPs 2E1 and 4A are the microsomal oxidases involved with fatty acid oxidation. Both enzymes can reduce molecular oxygen to produce prooxidant species, which, if not countered efficiently by antioxidants, create oxidative stress. In this theme article, we present the evidence that, in the context of hepatic steatosis, CYPs 2E1 and 4A could generate the “second hit” of cellular injury, particularly when antioxidant reserves are depleted, and propose ways in which this could contribute to the pathogenesis of NASH.

scholarly journals Huangkui Capsule Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Macrophage Activation by Suppressing Inflammation and Oxidative Stress in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jinfang Deng ◽  
Zhenpeng He ◽  
Xiuru Li ◽  
Wei Chen ◽  
Ziwen Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Macrophage Activation ◽  
Neutrophil Infiltration ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Myeloperoxidase Activity ◽  
Tnf Α ◽  
And Oxidative Stress

Background. Huangkui capsule (HKC) comprises the total flavonoid extract of flowers of Abelmoschus manihot (L.) Medicus. This study aimed to explore the effects of HKC on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and LPS-stimulated RAW 264.7 cells. Methods. Enzyme-linked immunosorbent assay, histopathology, spectrophotometry, and quantitative real-time polymerase chain reaction were used for the assessments. Statistical analysis was performed using a one-way analysis of variance. Results. LPS significantly increased lung inflammation, neutrophil infiltration, and oxidative stress and downregulated lung miR-451 expression. Treatment with HKC dramatically attenuated the lung wet/dry weight ratio, reduced the total cell count in the bronchoalveolar lavage fluid (BALF), and inhibited myeloperoxidase activity in the lung tissues 24 h after LPS challenge. Histopathological analysis demonstrated that HKC attenuated LPS-induced tissue oedema and neutrophil infiltration in the lung tissues. Additionally, the concentrations of tumour necrosis factor- (TNF-) α and interleukin- (IL-) 6 in BALF and IL-6 in the plasma reduced after HKC administration. Moreover, HKC could enhance glutathione peroxidase and catalase activities and upregulate the expression of miR-451 in the lung tissues. In vitro experiments revealed that HKC inhibited the production of nitric oxide, TNF-α, and IL-6 in LPS-induced RAW 264.7 cells and mouse primary peritoneal macrophages. Additionally, HKC downregulated LPS-induced transcription of TNF-α and IL-6 in RAW 264.7 cells. Conclusions. These findings suggest that HKC has anti-inflammatory and antioxidative effects that may protect mice against LPS-induced ALI and macrophage activation.

scholarly journals IL-23 Promotes Myocardial I/R Injury by Increasing the Inflammatory Responses and Oxidative Stress Reactions

2016 ◽  
Vol 38 (6) ◽  
pp. 2163-2172 ◽  
Author(s):  
Xiaorong Hu ◽  
Ruisong Ma ◽  
Jiajia Lu ◽  
Kai Zhang ◽  
Weipan Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Tunel Staining ◽  
Ischemia And Reperfusion ◽  
Stress Reactions ◽  
Sprague Dawley ◽  
Sod Activity ◽  
Myocardial Ischemia And Reperfusion ◽  
Tnf Α ◽  
And Oxidative Stress

Background/Aims: Inflammation and oxidative stress play an important role in myocardial ischemia and reperfusion (I/R) injury. We hypothesized that IL-23, a pro-inflammatory cytokine, could promote myocardial I/R injury by increasing the inflammatory response and oxidative stress. Methods: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO) group, ischemia and reperfusion (I/R) group, (IL-23 + I/R) group and (anti-IL-23 + I/R) group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH), creatine kinase (CK) and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-α and IL-6 were detected by Elisa. Results: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK (all P < 0.05). Meanwhile, IL-23 significantly increased the expression of eIL-17A, TNF-α and IL-6 and enhanced both the increase of the MDA level and the decrease of the SOD level induced by I/R (all P<0.05). IL-23 had no effect on the expression of HMGB1 (p > 0.05). All these effects were abolished by anti-IL-23 administration. Conclusion: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction.

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