The modulatory effects of exercise on the inflammatory and apoptotic markers in rats with 1,2-dimethylhydrazine-induced colorectal cancer

2020 ◽  
Vol 98 (3) ◽  
pp. 147-155 ◽  
Author(s):  
Saber Ghazizadeh Darband ◽  
Ehsan Saboory ◽  
Shirin Sadighparvar ◽  
Mojtaba Kaviani ◽  
Kazhal Mobaraki ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Exercise Program ◽  
Serum Levels ◽  
Aberrant Crypt Foci ◽  
Protective Effects ◽  
Histological Changes ◽  
Protein Levels ◽  
Tnf Α ◽  
Cox 2 ◽  
Underlying Mechanisms

This study aimed to investigate the underlying mechanisms in anti-tumorigenesis effects of exercise through evaluation of inflammation and apoptosis. Twenty-four Wistar rats were divided into control, exercise, 1,2-dimethylhydrazine (DMH), and DMH + exercise. After a week, rats in the DMH group were given DMH twice a week for 2 weeks. Animals in the exercise groups performed exercise on a treadmill 5 days/week for 8 weeks. After 8 weeks of training, levels of COX-2, PCNA, Bax, Bcl-2, and procaspase-3/cleaved caspase-3 were assessed. Histological changes, number of aberrant crypt foci (ACF), and serum levels of TNF-α and IL-6 were also analyzed. ACF number was significantly decreased following the exercise program. Protein levels of COX-2 and PCNA and serum levels of IL-6 and TNF-α were significantly elevated in the rats receiving DMH and downregulated after performing the exercise program (P < 0.05). Exercise upregulated apoptosis, which was evident from the increased Bax/Bcl2 ratio, and enhanced the expression levels of activated caspase-3 as compared to the DMH group. The colonic architecture was improved in DMH + exercise. Exercise can effectively attenuate DMH-induced increase of inflammatory markers. Exercise induces apoptosis at the downstream of the inflammatory response. Therefore, exercise may play a role as a moderator of inflammation to exert protective effects against colon cancer.

Tumor necrosis factor-α stimulates gastric epithelial cell proliferation

2005 ◽  
Vol 288 (1) ◽  
pp. G32-G38 ◽  
Author(s):  
Jiing Chyuan Luo ◽  
Vivian Yvonne Shin ◽  
Ying Hua Yang ◽  
William Ka Kei Wu ◽  
Yi Ni Ye ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Mucosal Injury ◽  
Epithelial Cell Line ◽  
Epithelial Cell Proliferation ◽  
Protein Levels ◽  
Tnf Α ◽  
Cox 2 ◽  
Underlying Mechanisms ◽  
Factor Α

TNF-α is a cytokine produced during gastric mucosal injury. We examined whether TNF-α could promote mucosal repair by stimulation of epithelial cell proliferation and explored further the underlying mechanisms in a rat gastric mucosal epithelial cell line (RGM-1). TNF-α treatment (1–10 ng/ml) for 12 or 24 h significantly increased cell proliferation but did not induce apoptosis in RGM-1 cells. TNF-α treatment significantly increased cytosolic phospholipase A2 and cyclooxygenase-2 (COX-2) protein expression and PGE2 level but did not affect the protein levels of EGF, basic fibroblast growth factor, and COX-1 in RGM-1 cells. The mRNA of TNF receptor (TNF-R) 2 but not of TNF-R1 was also increased. Dexamethasone dose dependently inhibited the stimulatory effect of TNF-α on cell proliferation, which was associated with a significant decrease in cellular COX-2 expression and PGE2 level. A selective COX-2 inhibitor 3-(3-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-5,5-dimethyl-5H-furan-2-one (DFU) by itself had no effect on basal cell proliferation but significantly reduced the stimulatory effect of TNF-α on RMG-1 cells. Combination of dexamethasone and DFU did not produce an additive effect. PGE2 significantly reversed the depressive action of dexamethasone on cell proliferation. These results suggest that TNF-α plays a regulatory role in epithelial cell repair in the gastric mucosa via the TNF-α receptor and activation of the arachidonic acid/PG pathway.

scholarly journals Regulation of Bcl-2 and the NF-kB Signaling Pathway by Succinyl Rotundic Acid in Livers of Rats with Alcoholic Hepatitis

2021 ◽  
Vol 25 (03) ◽  
pp. 730-734
Author(s):  
Yufang He
Keyword(s):  
Alcoholic Hepatitis ◽  
Caspase 3 ◽  
Serum Levels ◽  
Antagonistic Effect ◽  
Signal Pathways ◽  
High Dose ◽  
Protective Effects ◽  
Inflammatory Reactions ◽  
Protein Levels ◽  
Rotundic Acid

In this study, the protective effects of succinyl rotundic acids on alcoholic hepatitis in irradiated rats as well as the effects of Bcl-2-Bax-caspase-3 and the NF-kB signal pathways were studied. SD rats were divided into four groups randomly: normal; model; and succinyl rotundic acid low-, middle-, and high-dose groups. Distilled water, 60% ethanol and 60% ethanol +SRA, respectively, were given for 30 days. ELISA was used to measure serum levels of LDH, AST, ALT, NOS, NO, MDA, GSH and TG. Western blotting was used to measure protein levels of Bcl-2, Bax, caspase-3, NF-kB p 65, IKBA, HO-1, Nrf2 and CYP2E1. Compared with the model group, LDH, AST, ALT, NOS, NO, MDA and TG levels were lower in serum of low-, middle-, and high-dose groups (P < 0.01, P < 0.05 and P < 0.05 in all); GSH content was greater in serum of low-, middle- and high-dose groups (P < 0.05). Levels of Bcl-2, HO-1, and Nrf2 were greater (P < 0.01 in all); those of Bax, caspase-3, NF-kB p65, IKBA, and CYP2E1 were lower (P < 0.01 and P < 0.001 in all). These findings suggest that succinyl rotundic acid reduces inflammatory reactions by reducing levels of NOS and NO, regulating levels of Bcl-2, Bax, caspase-3, NF-kB, and anti-oxidative stress pathways, and has an antagonistic effect on alcoholic liver injury. The agent has potential to treat clinical alcoholic liver disease. © 2021 Friends Science Publishers

scholarly journals Protective Effects of Rutin Against Deltamethrin-Induced Hepatotoxicity and Nephrotoxicity in Rats via Regulation of Oxidative Stress, Inflammation and Apoptosis

2021 ◽  
Author(s):  
Sefa Küçükler ◽  
Fatih Mehmet Kandemir ◽  
Selçuk Özdemir ◽  
Selim Çomaklı ◽  
Cuneyt Caglayan
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Protective Effects ◽  
Type Ii ◽  
Protein Levels ◽  
Tnf Α ◽  
P38α Mapk ◽  
Liver And Kidney ◽  
Apoptotic Pathways ◽  
Parp 1

Abstract Deltamethrin (DLM) is a type-II pyrethroid synthetic insecticide that is extensively used for controlling mosquitoes, flies, pests, insects worldwide. Oxidative stress is one of the DLM toxicity mechanisms. This study was carried out to evaluate the likelihood protective effects of rutin (RUT), a natural antioxidant, against DLM-induced liver and kidney toxicities in rats. Hepatotoxicity and nephrotoxicity were evaluated after the rats were treated orally with DLM (1.28 mg/kg b.w.) alone or with RUT (25 and 50 mg/kg b.w.) for 30 days. DLM administration caused an increase in lipid peroxidation level and a decrease in activities of SOD, CAT, and GPx and GSH levels in the both tissues. DLM also increased serum ALT, AST, ALP, urea, and creatinine levels, while reduced nephrine levels in rats. In addition, DLM increased the activation of inflammatory and apoptotic pathways by decreasing Bcl-2 and increasing TNF-α, NF-κB, IL-1β, p38α MAPK, COX-2, iNOS, beclin-1, Bax, and caspase-3 protein levels and/or activities. Furthermore, DLM increased mRNA expression levels of PARP-1, VEGF and immunohistochemical expressions of c-fos in the tissues. RUT treatment significantly improved all examined parameters and restored the liver and kidney histopathological and immunohistochemical alterations. These findings demonstrate that RUT could be used to ameliorate hepatotoxicity and nephrotoxicity associated with oxidative stress, inflammation, and apoptosis in DLM-induced rats.

scholarly journals Protective Effects of Pelargonidin on Lipopolysaccharide-induced Hepatic Failure

2018 ◽  
Vol 13 (1) ◽  
pp. 1934578X1801300 ◽  
Author(s):  
Wonhwa Lee ◽  
Yuri Lee ◽  
Jaehong Kim ◽  
Jong-Sup Bae
Keyword(s):  
Liver Failure ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Serum Levels ◽  
Primary Response ◽  
Protective Effects ◽  
Toll Like Receptor 4 ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Lps Treatment

Pelargonidin (PEL) is a well-known red pigment found in plants and has important biological activities that are potentially beneficial for human health. The aim of this study was to investigate the effect of PEL on lipopolysaccharide (LPS)-induced liver failure in mice, and to elucidate its underlying molecular mechanisms. Liver failure was induced by LPS (15 mg/kg, i.p) in mice, and 12 h later, they were treated intravenously with PEL. Administration of LPS significantly increased mortality, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and inflammatory cytokines, and expression of toll-like receptor 4 (TLR4) protein; PEL treatment effectively countered these effects of LPS. Further, LPS treatment markedly increased the expression of myeloid differentiation primary response gene 88 (MyD88), phosphorylation of p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), and expressions of nuclear proteins, such as nuclear factor (NF)-κB and phosphorylated c-Jun. Additionally, LPS increased the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6. All these effects of LPS were attenuated by PEL. In addition, the LPS-mediated increase in the level of serum interferon (IFN)-β expression of the TLR-associated activator of IFN (TRIF) protein, and phosphorylation of IFN regulator factor 3 (IRF3) were reduced by PEL. Our results suggest that PEL attenuates LPS-induced liver damage by inhibition of the TLR-mediated inflammatory pathway and could be used to treat liver diseases.

scholarly journals Guaiane-Type Sesquiterpenoids From Dendranthema morifolium (Ramat.) S. Kitam Flowers Protect H9c2 Cardiomyocyte From LPS-Induced Injury

2019 ◽  
Vol 14 (7) ◽  
pp. 1934578X1986417
Author(s):  
Beibei Zhang ◽  
Mengnan Zeng ◽  
Meng Li ◽  
Wenjing Chen ◽  
Benke Li ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Creatine Phosphate ◽  
Cardiomyocyte Apoptosis ◽  
Exocyclic Double Bond ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Caspase 9 ◽  
Necrosis Factor Alpha ◽  
Thiazolyl Blue Tetrazolium Bromide ◽  
Tnf Α

This study investigated the protective effects of guaiane-type sesquiterpenoids isolated from Dendranthema morifolium (Ramat.) S. Kitam flowers on lipopolysaccharide (LPS)-induced injury in H9c2 cardiomyocyte. Cell viability was determined by thiazolyl blue tetrazolium bromide (MTT). The content of released tumor necrosis factor alpha (TNF- α) and interleukin 6 (IL-6) was evaluated by enzyme-linked immunosorbent assay. The levels of lactate dehydrogenase (LDH) and creatine phosphate kinase (CK) were measured by using commercial available kits. The protein expression levels of pelF2 α, GRP78, Bax, caspase-3, caspase-9, Bcl-2, LC3-II, and p62 were measured by in-cell Western. Flow cytometry was used to detect H9c2 cardiomyocyte apoptosis. Compounds 5, 7, 1, 8, and 2 exhibited the effects of cardioprotection and activity sequence enhancement. The levels of IL-6, TNF- α, LDH, CK, pelF2 α, GRP78, Bax, caspase-3, caspase-9, p62, and H9c2 cardiomyocyte apoptosis were increased in LPS-treated H9c2 cardiomyocyte, while those of Bcl-2 and LC3-II were decreased. These effects could be effectively reversed by compounds 5, 7, 1, 8, and 2. Results demonstrated that the guaiane-type sesquiterpenoids could prevent LPS-induced injury in cardiomyocyte by decreasing endoplasmic reticulum (ER) stress, apoptosis, and autophagy as well as downregulating the inflammatory mediators. In addition, the active groups of guaiane-type sesquiterpenoids might be the angelate at C-8 and the exocyclic double bond at C-11.

scholarly journals Valproic Acid Impacts the Growth of Growth Plate Chondrocytes

2020 ◽  
Vol 17 (10) ◽  
pp. 3675
Author(s):  
Hueng-Chuen Fan ◽  
Shih-Yu Wang ◽  
Yi-Jen Peng ◽  
Herng-Sheng Lee
Keyword(s):  
Valproic Acid ◽  
Short Stature ◽  
Growth Plate ◽  
Caspase 3 ◽  
Skeletal Growth ◽  
Growth Plate Chondrocytes ◽  
Protein Levels ◽  
Rat Growth ◽  
Cox 2 ◽  
Bone Abnormalities

A range of bone abnormalities including short stature have been reported to be associated with the use of antiepileptic drugs (AEDs) in children. Exactly how AEDs impact skeletal growth, however, is not clear. In the present study, rat growth plate chondrocytes were cultured to study the effects of AEDs, including valproic acid (VPA), oxcarbazepine (OXA), levetiracetam (LEV), lamotrigine (LTG), and topiramate (TPM) on the skeletal growth. VPA markedly reduced the number of chondrocytes by apoptosiswhile other AEDs had no effect. The apoptosis associated noncleaved and cleaved caspase 3, and caspases were increased by exposure to VPA, which up-regulated cyclooxygenase 2 (COX-2) mRNA and protein levels likely through histone acetylation. The COX-2 inhibitor NS-398 attenuated the effects of VPA up-regulating COX-2 expression and decreased VPA-induced caspase 3 expression. The use of VPA in children should be closely monitored or replaced, where appropriate, by AEDs which do not apparently affect the growth plate chondrocytes.

Protective Effects of Capparis sepiaria Root Extracts against Acetaminophen-Induced Hepatotoxicity in Wistar Rats

2012 ◽  
Vol 9 (1) ◽  
pp. 1-12 ◽  
Author(s):  
V. Madhavan ◽  
Ajay Shankar Pandey ◽  
Anita Murali ◽  
S. N. Yoganarasimhan
Keyword(s):  
Wistar Rats ◽  
Liver Weight ◽  
Serum Levels ◽  
Organic Analysis ◽  
Protective Effects ◽  
Protein Levels ◽  
Hepatic Transaminases ◽  
Ethanol Extracts ◽  
Hepatoprotective Drug ◽  
Important Drug

Capparis sepiaria L. known as Himsra is an important drug in Ayurveda. In this study extracts of the root of C. sepiaria were evaluated for their hepatoprotective potential on acetaminophen-induced hepatotoxicity in albino Wistar rats. The extent of hepatoprotection was evaluated by estimating the serum levels of hepatic transaminases (SGPT and SGOT), alkaline phosphatase (ALP), total protein (TP), and bilirubin (total and direct). Aqueous and ethanol extracts of C. sepiaria significantly reduced the increased liver weight as well as serum levels of SGPT, SGOT, ALP, and bilirubin, and normalized the reduced serum protein levels in the treated rats. These observations were supported by the results of histopathology studies as well. The extracts were also subjected to preliminary organic analysis and chromatographic studies including HPTLC finger print studies. The results indicate that the roots of C. sepiaria show significant hepatoprotective effect on acetaminophen-induced hepatotoxicity, thus substantiating its use as a potential hepatoprotective drug.

Effect of the Arctic terrestrial plant Ranunculus hyperboreus on LPS-induced inflammatory response via MAPK pathways

2018 ◽  
Vol 73 (7-8) ◽  
pp. 273-279 ◽  
Author(s):  
Chang-Suk Kong ◽  
Jung Im Lee ◽  
Fatih Karadeniz ◽  
Hojun Kim ◽  
Youngwan Seo
Keyword(s):  
Inflammatory Response ◽  
The Arctic ◽  
Mouse Macrophage ◽  
Ongoing Research ◽  
Protein Levels ◽  
Mapk Pathways ◽  
Tnf Α ◽  
Cox 2 ◽  
Bioactive Agents ◽  
Pro Inflammatory Cytokines

Abstract The Arctic flora hosts a limited number of species due to its extreme environmental conditions which also yield novel and unique secondary metabolites from withstanding plants. Considering a lack of research on bioactivity potential of Arctic flora, Ranunculus hyperboreus, an Arctic plant, was studied for its anti-inflammatory potential as a part of ongoing research on discovering novel natural bioactive products. Solvent-based fractions (H2O, n-BuOH, 85% aq. MeOH, n-hexane) from R. hyperboreus extract were observed to decrease the elevated nitrate amount during the inflammatory response of lipopolysaccharide-induced mouse macrophage RAW264.7 cells. To some extent, treatment with fractions was able to regulate the expression and protein levels of inflammation-related enzymes, iNOS and COX-2, and pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6. The most active fractions, H2O and 85% aq. MeOH, were suggested to exert their effect through suppressed activation of MAPK pathways, especially JNK. Based on the studies of same species, phenolic glycosides were suggested to be the main active ingredients. To our knowledge, this is the first report of any bioactivity of R. hyperboreus which could be a valuable source of natural bioactive agents against inflammation.

scholarly journals Modulation of COX-2 and NADPH oxidase-4 by Alpha-lipoic acid ameliorates busulfan-induced pulmonary injury in rats.

2021 ◽  
Author(s):  
Mona Elhadidy ◽  
Ahlam Elmasry ◽  
Hassan Reda Hassan Elsayed ◽  
Mohammad H El-Nablaway ◽  
Shereen Hamed ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lipoic Acid ◽  
Caspase 3 ◽  
Smooth Muscle Actin ◽  
Male Rats ◽  
Nadph Oxidase 4 ◽  
Tnf Α ◽  
Cox 2 ◽  
Index Ratio ◽  
Sirius Red

Abstract purpose: Busulfan is an antineoplastic drug that produces pulmonary fibrosis. This study aimed to explore the potential protective effect of α-lipoic acid on busulfan-induced pulmonary fibrosis in rats.Methods: Twenty-four adult male rats were divided into four groups: control, α-lipoic acid (ALA), busulfan, and busulfan plus α-lipoic acid. Lung index ratio, serum level of proinflammatory cytokine were assessed. The activities of antioxidant enzymes and lipid peroxidation products were estimated in the lung tissues in addition to histopathological analyses. The deposition of the collagen in the lung tissues was evaluated by Sirius red staining. The expressions of α-smooth muscle actin (α-SMA), TNF-α, and Caspase 3 were determined immunohistochemically. The pulmonary expression of COX-2 and NOX-4 mRNA were assessed using qRT-PCR.Results: administration of ALA significantly ameliorated BUS-induced pulmonary fibrosis, besides the upregulation of antioxidants, and downregulation of pro-inflammatory cytokines. Also, it reduced collagen deposition associated with a decreased expression of α-SMA, TNF-α, and Caspase 3 in the lung tissues. Moreover, ALA significantly upregulated the expression of COX-2 concomitant with the downregulation of elevated NOX-4.Conclusion: ALA attenuates the lung cytotoxicity of busulfan through its anti-inflammatory, anti-apoptotic, and antifibrotic effects that may be mediated by upregulation of COX-2 and downregulation of NOX-4.

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