scholarly journals Elevated Apoptosis in the Liver of Dairy Cows with Ketosis

2017 ◽  
Vol 43 (2) ◽  
pp. 568-578 ◽  
Author(s):  
Xiliang Du ◽  
Liang Chen ◽  
Dan Huang ◽  
Zhicheng Peng ◽  
Chenxu Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dairy Cows ◽  
Caspase 3 ◽  
Hepatic Damage ◽  
Related Factor ◽  
Apoptosis Pathway ◽  
P53 Expression ◽  
Amyloid A ◽  
Hepatic Oxidative Stress ◽  
Glutamyl Transferase

Background/Aims: Dairy cows with ketosis are characterized by oxidative stress and hepatic damage. The aim of this study was to investigate hepatic oxidative stress and the apoptotic status of ketotic cows, as well as the underlying apoptosis pathway. Methods: The blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase (GGT) activities and the haptoglobin (HP), serum amyloid A (SAA) and serum apoptotic cytokeratin 18 neo-epitope M30 (CK18 M30) concentrations were determined by commercially available kits and ELISA kits, respectively. Liver histology, TUNEL and Oil red O staining were performed in liver tissue samples. TG contents were measured using an enzymatic kit; Caspase 3 assays were carried out using the Caspase 3 activity assay kit; oxidation and antioxidant markers were measured using biochemical kits; apoptosis pathway were determined by qRT-PCR and western blot. Results: Ketotic cows displayed hepatic fat accumulation. The hepatic malondialdehyde (MDA) content was significantly increased, but the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were markedly decreased in ketotic cows compared with control cows, indicating that ketotic cows displayed severe oxidative stress. Significantly higher serum levels of the hepatic damage markers AST, ALT, GGT and GLDH were observed in ketotic cows than in control cows. The blood concentration of the apoptotic marker CK18 M30 and the number of TUNEL-positive cells in the liver of ketotic cows were 1.19- and 2.61-fold, respectively, higher than the values observed in control cows. Besides, Caspase 3 activity was significantly increased in the liver of ketosis cows. Importantly, the levels of phosphorylated c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) were significantly increased but the level of phosphorylated extracellular signal-regulated kinase1/2 (ERK1/2) was markedly decreased, which further promoted tumor protein 53 (p53) expression and inhibited nuclear factor E2-related factor 2 (Nrf2) expression. The apoptosis-related molecules p21, MDM2, Caspase 3, Caspase 9 and Bax were expressed at significantly higher levels in ketotic cows than in healthy cows, whereas the anti-apoptosis molecule Bcl-2 was expressed at significantly lower levels. Conclusions: Based on these results, ketotic cows display severe hepatic oxidative stress. The hepatic MAPK-p53-Nrf2 apoptotic pathway is over induced and partially mediated apoptotic damage in the liver.

scholarly journals Keap1 deletion accelerates mutant K-ras/p53-driven cholangiocarcinoma

2020 ◽  
Vol 318 (3) ◽  
pp. G419-G427 ◽  
Author(s):  
Tatsuhide Nabeshima ◽  
Shin Hamada ◽  
Keiko Taguchi ◽  
Yu Tanaka ◽  
Ryotaro Matsumoto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cancer Progression ◽  
Stress Responses ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Related Factor ◽  
Loss Of Function ◽  
P53 Expression ◽  
Nrf2 Activation

The activation of the Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) pathway contributes to cancer progression in addition to oxidative stress responses. Loss-of-function Keap1 mutations were reported to activate Nrf2, leading to cancer progression. We examined the effects of Keap1 deletion in a cholangiocarcinoma mouse model using a mutant K-ras/ p53 mouse. Introduction of the Keap1 deletion into liver-specific mutant K-ras/ p53 expression resulted in the formation of invasive cholangiocarcinoma. Comprehensive analyses of the gene expression profiles identified broad upregulation of Nrf2-target genes such as Nqo1 and Gstm1 in the Keap1-deleted mutant K-ras/ p53 expressing livers, accompanied by upregulation of cholangiocyte-related genes. Among these genes, the transcriptional factor Sox9 was highly expressed in the dysplastic bile duct. The Keap-Nrf2-Sox9 axis might serve as a novel therapeutic target for cholangiocarcinoma. NEW & NOTEWORTHY The Keap1-Nrf2 system has a wide variety of effects in addition to the oxidative stress response in cancer cells. Addition of the liver-specific Keap1 deletion to mice harboring mutant K-ras and p53 accelerated cholangiocarcinoma formation, together with the hallmarks of Nrf2 activation. This process involved the expansion of Sox9-positive cells, indicating increased differentiation toward the cholangiocyte phenotype.

scholarly journals Structural Characterization and Antioxidant Activity of Polysaccharides from Athyrium multidentatum (Doll.) Ching in d-Galactose-Induced Aging Mice via PI3K/AKT Pathway

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3364 ◽  
Author(s):  
Liang Jing ◽  
Jing-Ru Jiang ◽  
Dong-Mei Liu ◽  
Ji-Wen Sheng ◽  
Wei-Fen Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Weight ◽  
Protein Expression ◽  
Mrna Expression ◽  
Caspase 3 ◽  
Akt Pathway ◽  
Protective Mechanism ◽  
Related Factor ◽  
Bax Protein ◽  
Gene And Protein Expression

The purpose of this study was to characterize the polysaccharides from Athyrium multidentatum (Doll.) Ching (AMC) rhizome and explore the protective mechanism against d-galactose-induced oxidative stress in aging mice. Methods: A series of experiments, including molecular weight, monosaccharide composition, Fourier transform infrared (FT-IR) spectroscopy, and 1H nuclear magnetic resonance (1H NMR) spectroscopy were carried out to characterize AMC polysaccharides. The mechanism was investigated exploring d-galactose-induced aging mouse model. Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) and western blotting assays were performed to assess the gene and protein expression in liver. Key findings: Our results showed that AMC polysaccharides were mainly composed of mannose (Man), rhamnose (Rha), glucuronic acid (Glc A), glucose (Glc), galactose (Gal), arabinose (Ara), and fucose (Fuc) in a molar ratio of 0.077:0.088:0.09:1:0.375:0.354:0.04 with a molecular weight of 33203 Da (Mw). AMC polysaccharides strikingly reversed d-galactose-induced changes in mice, including upregulated phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor-erythroid 2-related factor 2 (Nrf2), forkhead box O3a (FOXO3a), and hemeoxygenase-1 (HO-1) mRNA expression, raised Bcl-2/Bax ratio, downregulated caspase-3 mRNA expression, enhanced Akt, phosphorylation of Akt (p-Akt), Nrf2 and HO-1 protein expression, decreased caspase-3, and Bax protein expression. Conclusion: AMC polysaccharides attenuated d-galactose-induced oxidative stress and cell apoptosis by activating the PI3K/AKT pathway, which might in part contributed to their anti-aging activity.

Epimedium koreanum Ameliorates Oxidative Stress-Mediated Liver Injury by Activating Nuclear Factor Erythroid 2-Related Factor 2

2018 ◽  
Vol 46 (02) ◽  
pp. 469-488 ◽  
Author(s):  
Ji Yun Jung ◽  
Sang Mi Park ◽  
Hae Li Ko ◽  
Jong Rok Lee ◽  
Chung A Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Hepg2 Cells ◽  
Liver Diseases ◽  
Caspase 3 ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Activation ◽  
Anti Oxidant

Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100[Formula: see text][Formula: see text]g/mL) significantly inhibited AA[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly(ADP-ribose) polymerase. EKE attenuated hydrogen peroxide production, glutathione depletion, and mitochondrial membrane dysfunction. EKE also increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), transactivated anti-oxidant response element harboring luciferase activity, and induced the expression of anti-oxidant genes. Furthermore, the cytoprotective effect of EKE against AA[Formula: see text][Formula: see text][Formula: see text]iron was blocked in Nrf2 knockout cells. Ultra-performance liquid chromatography analysis showed that EKE contained icariin, icaritin, and quercetin; icaritin and quercetin were both found to protect HepG2 cells from AA[Formula: see text][Formula: see text][Formula: see text]iron via Nrf2 activation. In a CCl4-induced mouse model of liver injury, pretreatment with EKE (300[Formula: see text]mg/kg) for four consecutive days ameliorated CCl4-mediated increases in serum aspartate aminotransferase activity, histological activity index, hepatic parenchyma degeneration, and inflammatory cell infiltration. EKE also decreased the number of nitrotyrosine-, 4-hydroxynonenal-, cleaved caspase-3-, and cleaved poly(ADP-ribose) polymerase-positive cells in hepatic tissues. These results suggest EKE is a promising candidate for the prevention or treatment of oxidative stress-related liver diseases via Nrf2 activation.

scholarly journals Xylopine Induces Oxidative Stress and Causes G2/M Phase Arrest, Triggering Caspase-Mediated Apoptosis by p53-Independent Pathway in HCT116 Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Luciano de Souza Santos ◽  
Valdenizia Rodrigues Silva ◽  
Leociley Rocha Alencar Menezes ◽  
Milena Botelho Pereira Soares ◽  
Emmanoel Vilaça Costa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Cancer Cell ◽  
Caspase 3 ◽  
Cancer Cell Lines ◽  
Apoptosis Pathway ◽  
Phase Arrest ◽  
M Phase ◽  
Induced Apoptosis ◽  
Hct116 Cells

Xylopine is an aporphine alkaloid that has cytotoxic activity to cancer cells. In this study, the underlying mechanism of xylopine cytotoxicity was assessed in human colon carcinoma HCT116 cells. Xylopine displayed potent cytotoxicity in different cancer cell lines in monolayer cultures and in a 3D model of cancer multicellular spheroids formed from HCT116 cells. Typical morphology of apoptosis, cell cycle arrest in the G2/M phase, increased internucleosomal DNA fragmentation, loss of the mitochondrial transmembrane potential, and increased phosphatidylserine externalization and caspase-3 activation were observed in xylopine-treated HCT116 cells. Moreover, pretreatment with a caspase-3 inhibitor (Z-DEVD-FMK), but not with a p53 inhibitor (cyclic pifithrin-α), reduced xylopine-induced apoptosis, indicating induction of caspase-mediated apoptosis by the p53-independent pathway. Treatment with xylopine also caused an increase in the production of reactive oxygen/nitrogen species (ROS/RNS), including hydrogen peroxide and nitric oxide, but not superoxide anion, and reduced glutathione levels were decreased in xylopine-treated HCT116 cells. Application of the antioxidant N-acetylcysteine reduced the ROS levels and xylopine-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway. In conclusion, xylopine has potent cytotoxicity to different cancer cell lines and is able to induce oxidative stress and G2/M phase arrest, triggering caspase-mediated apoptosis by the p53-independent pathway in HCT116 cells.

scholarly journals Does Hepatic Oxidative Stress Enhance Activation of Nuclear Factor-E2-Related Factor in Patients with Nonalcoholic Steatohepatitis?

2014 ◽  
Vol 20 (3) ◽  
pp. 538-543 ◽  
Author(s):  
Yurimi Takahashi ◽  
Yoshimasa Kobayashi ◽  
Kazuhito Kawata ◽  
Kinya Kawamura ◽  
Shinichi Sumiyoshi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nonalcoholic Steatohepatitis ◽  
Related Factor ◽  
Nuclear Factor ◽  
Hepatic Oxidative Stress

scholarly journals Securidaca inappendiculata Polyphenol Rich Extract Counteracts Cognitive Deficits, Neuropathy, Neuroinflammation and Oxidative Stress in Diabetic Encephalopathic Rats via p38 MAPK/Nrf2/HO-1 Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaojun Pang ◽  
Emmanuel Ayobami Makinde ◽  
Fredrick Nwude Eze ◽  
Opeyemi Joshua Olatunji
Keyword(s):  
Oxidative Stress ◽  
P38 Mapk ◽  
Caspase 3 ◽  
Diabetic Rats ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Diabetic Encephalopathy ◽  
Y Maze ◽  
Securidaca Inappendiculata

Diabetic encephalopathy is one of the serious emerging complication of diabetes. Securidaca inappendiculata is an important medicinal plant with excellent antioxidant and anti-inflammatory properties. This study investigated the neuroprotective effects of S. inappendiculata polyphenol rich extract (SiPE) against diabetic encephalopathy in rats and elucidated the potential mechanisms of action. Type 2 diabetes mellitus (T2DM) was induced using high fructose solution/intraperitoneal injection of streptozotocin and the diabetic rats were treated with SiPE (50, 100 and 200 mg/kg) for 8 weeks. Learning and memory functions were assessed using the Morris water and Y maze tests, depressive behaviour was evaluated using forced swimming and open field tests, while neuropathic pain assessment was assessed using hot plate, tail immersion and formalin tests. After the experiments, acetylcholinesterase (AChE), oxidative stress biomarkers and proinflammatory cytokines, caspase-3 and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) were determined by ELISA kits. In addition, the expression levels of p38, phospho-p38 (p-p38), nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined by western blot analyses. The results indicated that SiPE administration significantly lowered blood glucose level, attenuated body weight loss, thermal/chemical hyperalgesia, improved behavioural deficit in the Morris water maze, Y maze test and reduced depressive-like behaviours. Furthermore, SiPE reduced AChE, caspase-3, NF-κB, malonaldehyde malondialdehyde levels and simultaneously increased antioxidant enzymes activity in the brain tissues of diabetic rats. SiPE administration also significantly suppressed p38 MAPK pathway and upregulated the Nrf2 pathway. The findings suggested that SiPE exerted antidiabetic encephalopathy effects via modulation of oxidative stress and inflammation.

scholarly journals Sodium tanshinone IIA sulfonate attenuates tumor oxidative stress and enhances apoptosis in an intermittent hypoxia mouse model

2019 ◽  
Author(s):  
Xiao-Bin Zhang ◽  
Xiao-Yang Chen ◽  
Xiao-Man Su ◽  
Hui-Qing Zeng ◽  
Yi-Ming Zeng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Western Blotting ◽  
Intermittent Hypoxia ◽  
Caspase 3 ◽  
Tanshinone Iia ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Related Factor ◽  
Obstructive Sleep ◽  
Sodium Tanshinone Iia Sulfonate

Abstract Objective The present study was designed to determine the effect of sodium tanshinone IIA sulfonate (TSA) on tumor oxidative stress and apoptosis in a mouse model of intermittent hypoxia (IH) which was considered a novel feature of obstructive sleep apnea. Materials and methods Mice were randomly assigned to control (normoxia) group (CTL), control plus TSA (CTL+TSA) group, IH group, and IH plus TSA (IH+TSA) group. The IH exposure lasted for 5 weeks. TSA was intraperitoneally injected in the CTL+TSA and IH+TSA group. Malondialdehyde (MDA) and superoxide dismutase (SOD) were detected for tumor oxidative stress levels. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and western blotting of Bax, Cleaved Caspase-3 were conducted for evaluating tumor apoptotic levels. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and NF-κB were also evaluated by western blotting. Results Compared with the CTL group, mice exposed to the IH had higher MDA and lower SOD levels, and the TUNEL-positive cell rate, Bax and Cleaved Caspase-3 expressive levels were decreased in the IH group. The oxidative stress indexes were suppressed and the apoptotic levels were upregulated after treatment with TSA under the IH condition. The lower Nrf2 and higher NF-κB levels can be reversed by tretment with TSA under the IH condition. Conclusions The IH contributes to high oxidative stress and low apoptosis in tumor-bearing mice. TSA appears to improve IH-induced oxidative stress and apoptosis via Nrf2/NF-κB signaling pathway.

Hepatoprotective Effects of Red Cabbage in Hypercholesterolemic Diet-induced Oxidative Stressed Rabbits

2020 ◽  
Vol 16 (4) ◽  
pp. 469-480 ◽  
Author(s):  
Faiza Ashfaq ◽  
Masood S. Butt ◽  
Ahmad Bilal ◽  
Hafiz A.R. Suleria
Keyword(s):  
Oxidative Stress ◽  
Aqueous Extract ◽  
Hepatosomatic Index ◽  
Red Cabbage ◽  
Mild Degree ◽  
Hepatic Oxidative Stress ◽  
Hypercholesterolemic Diet ◽  
Endogenous Antioxidant ◽  
The Masses ◽  
Glutamyl Transferase

Background: Diet-disease linkages are getting immense attention of the scientific fraternity. In this regard, red cabbage was assessed against hypercholesterolemic and related oxidative damage. Nowadays, plant bioactives are gaining immense attention among the masses to mitigate lifestyle related malfunctions. Considering phytochemistry and cost-effectiveness, the current project was designed to probe the bioefficacy red cabbage against hypercholesterolemic diet related oxidative stress in the liver. Methods: The red cabbage and its aqueous extract were tested on male white New Zealand rabbits for 12 weeks. Two studies were conducted based on dietary regimens; normal and hypercholesterolemic diet (1% cholesterol). At termination, overnight fasted rabbits were sacrificed to assess serum specific and tissues biomarkers of hepatic oxidative stress alongside, hepatosomatic index and histopathology were studied. Results: In hypercholesterolemic diet induced oxidative stressed rabbits, the supplementation of red cabbage and its aqueous extract suppressed the leakage of liver functioning enzymes in sera up to 15.63 and 12.70% (alanine transaminase), 13.88 and 9.55% (alkaline phosphatase), 12.96 and 8.82% (γ-glutamyl transferase) and 10.77 and 6.15% (total bilirubin). Besides, the respective diets also portrayed considerable reduction in hepatic lipid peroxidation up to 29.60 and 23.63% thus improved endogenous antioxidant enzymes; superoxide dismutase (17.97 and 15.92%) and catalase (24.39 and 20.98%). Furthermore, hepatosomatic index expounded a significant impact of treatments on oxidative stressed rabbits alongside mild degree of fibrotic and necrotic changes in their hepatic parenchyma was rectified by red cabbage, whereas red cabbage extract demonstrated slower rate of amelioration. Conclusion: In the nutshell, dietary inclusions based on red cabbage have shown higher restorative potential against hepatic oxidative stress as compared to red cabbage aqueous extract.

Milk metabolites, proteins and oxidative stress markers in dairy cows suffering from Staphylococcus aureus subclinical mastitis with or without spontaneous cure

2021 ◽  
pp. 1-4
Author(s):  
Nasim Tabatabaee ◽  
Mohammad Heidarpour ◽  
Babak Khoramian
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Antioxidant Capacity ◽  
Dairy Cows ◽  
Total Antioxidant Capacity ◽  
Acute Phase Proteins ◽  
Subclinical Mastitis ◽  
Amyloid A ◽  
Spontaneous Cure ◽  
Total Antioxidant

Abstract Our objective was to evaluate relationships between milk components (acute phase proteins, enzymes, metabolic parameters and oxidative indices) and the spontaneous cure outcome of Staphylococcus aureus subclinical mastitis in dairy cows. The values of haptoglobin, serum amyloid A (SAA), malondialdehyde (MDA), total antioxidant capacity, milk urea nitrogen (MUN), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), electrolytes (Cl and K), total protein, albumin, α-lactalbumin, β-lactoglobulin, and immunoglobulin were measured in milk samples of S. aureus subclinical mastitis cows with spontaneous cure (n = 23), S. aureus subclinical mastitis cows without spontaneous cure (n = 29) and healthy cows (n = 23). The comparison of measured parameters revealed that subclinical mastitis cows with spontaneous cure had lower ALP and haptoglobin concentrations both at diagnosis and after cure (P < 0.05). In contrast, total antioxidant capacity and MDA concentration in subclinical mastitis cows without spontaneous cure significantly increased with time (P < 0.05). We can suggest that elevated haptoglobin concentration and higher ALP activity indicative of enhanced oxidative stress could potentially serve as early diagnostic indicators of chronic disease and the persistence of S. aureus subclinical mastitis in dairy cows.

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