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.

Increased severity of alcoholic liver injury in female rats: role of oxidative stress, endotoxin, and chemokines

2001 ◽  
Vol 281 (6) ◽  
pp. G1348-G1356 ◽  
Author(s):  
Amin A. Nanji ◽  
Kalle Jokelainen ◽  
Maryam Fotouhinia ◽  
Amir Rahemtulla ◽  
Peter Thomas ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Liver Injury ◽  
Fish Oil ◽  
Nonheme Iron ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Alcoholic Liver Injury ◽  
Tnf Α ◽  
Cox 2

Alcoholic liver injury is more severe and rapidly developing in women than men. To evaluate the reason(s) for these gender-related differences, we determined whether pathogenic mechanisms important in alcoholic liver injury in male rats were further upregulated in female rats. Male and age-matched female rats (7/group) were fed ethanol and a diet containing fish oil for 4 wk by intragastric infusion. Dextrose isocalorically replaced ethanol in control rats. We analyzed liver histopathology, lipid peroxidation, cytochrome P-450 (CYP)2E1 activity, nonheme iron, endotoxin, nuclear factor-κB (NF-κB) activation, and mRNA levels of cyclooxygenase-1 (COX-1) and COX-2, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2). Alcohol-induced liver injury was more severe in female vs. male rats. Female rats had higher endotoxin, lipid peroxidation, and nonheme iron levels and increased NF-κB activation and upregulation of the chemokines MCP-1 and MIP-2. CYP2E1 activity and TNF-α and COX-2 levels were similar in male and female rats. Remarkably, female rats fed fish oil and dextrose also showed necrosis and inflammation. Our findings in ethanol-fed rats suggest that increased endotoxemia and lipid peroxidation in females stimulate NF-κB activation and chemokine production, enhancing liver injury. TNF-α and COX-2 upregulation are probably important in causing liver injury but do not explain gender-related differences.

Vascular endothelial function is improved by oral glycine treatment in aged rats

2015 ◽  
Vol 93 (6) ◽  
pp. 465-473 ◽  
Author(s):  
Jaime H. Gómez-Zamudio ◽  
Rebeca García-Macedo ◽  
Martha Lázaro-Suárez ◽  
Maximiliano Ibarra-Barajas ◽  
Jesús Kumate ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mrna Expression ◽  
Interleukin 1 ◽  
Aged Rats ◽  
Sprague Dawley ◽  
Response Curves ◽  
Proinflammatory Mediators ◽  
Nadph Oxidase 4 ◽  
Tnf Α ◽  
Cox 2

Glycine has been used to reduce oxidative stress and proinflammatory mediators in some metabolic disorders; however, its effect on the vasculature has been poorly studied. The aim of this work was to explore the effect of glycine on endothelial dysfunction in aged rats. Aortic rings with intact or denuded endothelium were obtained from untreated or glycine-treated male Sprague–Dawley rats at 5 and 15 months of age. Concentration–response curves to phenylephrine (PHE) were obtained from aortic rings incubated with NG-nitro-l-arginine methyl ester (l-NAME), superoxide dismutase (SOD), indomethacin, SC-560, and NS-398. Aortic mRNA expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase 4 (NOX-4), cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2), tumour necrosis factor (TNF)-α, and interleukin-1 β was measured by real time RT–PCR. The endothelial modulation of the contraction by PHE was decreased in aortic rings from aged rats. Glycine treatment improved this modulator effect and increased relaxation to acetylcholine. Glycine augmented the sensitivity for PHE in the presence of l-NAME and SOD. It also reduced the contraction by incubation with indomethacin, SC-560, and NS-398. Glycine increased the mRNA expression of eNOS and decreased the expression of COX-2 and TNF-α. Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability.

scholarly journals The potential therapeutic effect of red clover’s extract against an induced molecular neurodegeneration in male rats

2020 ◽  
Vol 1 (1) ◽  
pp. 39-50
Author(s):  
Al-Sayeda A. Newairy ◽  
◽  
Fatma A. Hamaad ◽  
Mayssaa M. Wahby ◽  
Heba M. Abdou ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Treated Group ◽  
Oxidative Status ◽  
Male Rats ◽  
Biochanin A ◽  
Brain Extract ◽  
Monoamine Neurotransmitters ◽  
Electron Microscopic ◽  
Tnf Α ◽  
Cox 2

Monosodium glutamate (MSG) is a flavor enhancer. Oxidative neurotoxicity of MSG is well established. This study explored the therapeutic effect of red clover’s (RC) extract against MSG–induced neurodegeneration. HPLC-analysis revealed that formononetin, genistein, daidzein and biochanin A are the major isoflavones in RC’s extract. Four equal groups of male rats were used: control group, MSG-treated group, MSG plus RC-treated group and RC-treated group. The gene expression of iNOS, TNF-α, Cox-2 and p53 were evaluated in the brain extract using RT-PCR. The histological and electron microscopic examinations as well as the cholinergic function, the neurotransmitters and the oxidative status were also assessed. The MSG significantly up regulated the expression levels of iNOS, TNF-α, Cox-2 and p53. The activity of acetyl cholinesterase (AChE), the monoamine neurotransmitters and the oxidative status as well as the histological and electron microscopic examinations confirmed the MSG-induced neurodegeneration. The administration of RC plus MSG diminished the expression of the inflammatory cytokines, the activity of AChE and the levels of monoamine neurotransmitters. RC also ameliorated the oxidative stress and the histological and the electron microscopic alterations. Accordingly, the present study provides an insight on the antioxidative and anti-inflammatory potentials of RC’s extract as neuroprotective agent.

scholarly journals Neuroprotective Effect of Fisetin Through Suppression of IL-1R/TLR Axis and Apoptosis in Pentylenetetrazole-Induced Kindling in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Saima Khatoon ◽  
Nidhi Bharal Agarwal ◽  
Mohammed Samim ◽  
Ozair Alam
Keyword(s):  
Cytochrome C ◽  
Caspase 3 ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Seizure Threshold ◽  
Experimental Epilepsy ◽  
Kindling Model ◽  
Histological Alterations ◽  
Tnf Α ◽  
Cox 2

Epilepsy is a complex neurological disorder, characterized by frequent electrical activity in brain regions. Inflammation and apoptosis cascade activation are serious neurological sequelae during seizures. Fisetin (3, 3′,4′,7-tetrahydroxyflavone), a flavonoid molecule, is considered for its effective anti-inflammatory and anti-apoptotic properties. This study investigated the neuroprotective effect of fisetin on experimental epilepsy. For acute studies, increasing current electroshock (ICES) and pentylenetetrazole (PTZ)-induced seizure tests were performed to evaluate the antiseizure activity of fisetin. For the chronic study, the kindling model was established by the administration of PTZ in subconvulsive dose (25 mg/kg, i.p.). Mice were treated with fisetin (5, 10, and 20 mg/kg, p.o.) to study its probable antiseizure mechanism. The kindled mice were evaluated for seizure scores. Their hippocampus and cortex were assessed for neuronal damage, inflammation, and apoptosis. Histological alterations were observed in the hippocampus of the experimental mice. Levels of high mobility group box 1 (HMGB1), Toll-like receptor-4 (TLR-4), interleukin-1 receptor 1 (IL-1R1), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed in the hippocampus and cortex by ELISA. The immunoreactivity and mRNA expressions of nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), cytochrome C, and caspase-3 were quantified by immunohistochemical analysis and real-time PCR. Phosphorylation ELISA was performed to evaluate AkT/mTOR (mammalian target of rapamycin) activation in the hippocampus and cortex of the kindled mice. The results showed that fisetin administration increased the seizure threshold current (STC) in the ICES test. In PTZ-induced seizures, fisetin administration increased the latency for myoclonic jerks (MJs) and generalized seizures (GSs). In the PTZ-induced kindling model, fisetin administration dose-dependently suppressed the development of kindling and the associated neuronal damage in the experimental mice. Further, fisetin administration ameliorated kindling-induced neuroinflammation as evident from decreased levels of HMGB1, TLR-4, IL-1R1, IL-1β, IL-6, and TNF-α in the hippocampus and cortex of the kindled mice. Also, the immunoreactivity and mRNA expressions of inflammatory molecules, NF-κB, and COX-2 were decreased with fisetin administration in the kindled animals. Decreased phosphorylation of the AkT/mTOR pathway was reported with fisetin administration in the hippocampus and cortex of the kindled mice. The immunoreactivity and mRNA expressions of apoptotic molecules, cytochrome C, and caspase-3 were attenuated upon fisetin administration. The findings suggest that fisetin shows a neuroprotective effect by suppressing the release of inflammatory and apoptosis molecules and attenuating histological alterations during experimental epilepsy.

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

Heliyon ◽  
2021 ◽  
pp. e08171
Author(s):  
Mona G. Elhadidy ◽  
Ahlam Elmasry ◽  
Hassan Reda Hassan Elsayed ◽  
Mohammad El-Nablaway ◽  
Shereen Hamed ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Lipoic Acid ◽  
Alpha Lipoic Acid ◽  
Pulmonary Injury ◽  
Nadph Oxidase 4 ◽  
Cox 2

scholarly journals Total Glucosides of Danggui Buxue Tang Attenuate BLM-Induced Pulmonary Fibrosis via Regulating Oxidative Stress by Inhibiting NOX4

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Ping Zhao ◽  
Wen-Cheng Zhou ◽  
De-Lin Li ◽  
Xiao-Ting Mo ◽  
Liang Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Fibrosis ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Type I ◽  
Model Group ◽  
Sod Activity ◽  
Danggui Buxue Tang ◽  
Nadph Oxidase 4

Pulmonary fibrosis (PF) is a serious chronic lung disease with unknown pathogenesis. Researches have confirmed that oxidative stress which is regulated by NADPH oxidase-4 (NOX4), a main source of reactive oxygen species (ROS), is an important molecular mechanism underlying PF. Previous studies showed that total glucosides of Danggui Buxue Tang (DBTG), an extract from a classical traditional Chinese herbal formula, Danggui Buxue Tang (DBT), attenuated bleomycin-induced PF in rats. However, the mechanisms of DBTG are still not clear. We hypothesize that DBTG attenuates PF through regulating the level of oxidative stress by inhibiting NOX4. And we found that fibrosis indexes hydroxyproline (HYP) and type I collagen (Col-I) were lower in DBTG groups compared with the model group. In addition, the expression of transforming growth factor-β1 (TGF-β1) and expression of alpha smooth muscle actin (α-SMA) were also much more decreased than the model group. For oxidative stress indicators, DBTG blunted the decrease of superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and the increase in malondialdehyde (MDA), 8-iso-prostaglandin in lung homogenates. Treatment with DBTG restrained the expression of NOX4 compared to the model group. Present study confirms that DBTG inhibits BLM-induced PF by modulating the level of oxidative stress via suppressing NOX4.

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.

scholarly journals IN SILICO DOCKING STUDIES ON KAEMPFERITRIN WITH DIVERSE INFLAMMATORY AND APOPTOTIC PROTEINS FUNCTIONAL APPROACH TOWARDS THE COLON CANCER

2017 ◽  
Vol 9 (9) ◽  
pp. 199
Author(s):  
Mydhili Govindarasu ◽  
Mariyappan Palani ◽  
Manju Vaiyapuri
Keyword(s):  
Colon Cancer ◽  
Cytochrome P450 ◽  
Amino Acid ◽  
Protein Kinase ◽  
Caspase 3 ◽  
Tnf Α ◽  
Different Types ◽  
Inflammatory Proteins ◽  
Cox 2 ◽  
Apoptotic Proteins

Objective: The objective of this research was to formulate the binding energies and interaction of amino acid residues in kaempferitrin with different types of apoptotic and inflammatory proteins of colon cancer.Methods: AutoDock Vina and MGL tool were used for docking calculations. Both programs require the pdbqt input files and allow for flexibility of all the torsional bonds of small molecules. Discovery Studio Visualizer v3.5 was used for removal of water molecules and ligands and the pymol program was used to do analysis of the docking with various apoptotic proteins BAX, Bcl-2, COX-2, Protein kinase B.Results: In our study was developed binding energy scoring function of kaempferitrin docked with different types of inflammatory proteins and apoptotic proteins. Binding score values for-6.9 (BAX),-7.2 (Bcl-2),-7.3 (caspase-3),-8.8 (Cox-2),-7.4 (Cytochrome P450),-6.7 (Proteinase kinase B),-8.0 (TNF-α) and-7.2 (VEGF) kcal/mol, respectively. Amino acid interaction of kaempferitrin with proteins for ARG-25, LEU-52, ASN-54, PHE-55, GLU-17, LYS-14, TRP-22, THR-21 GLY-16 (Protein Kinase B), ASP-102, ASN-48, GLN-52, ASP-104 (BAX), GLU-176, TRP-173, GLU-132, PHE-135 (Bcl-2), SER-249, ASP-2, ASN-208, GLN-217, LEU-242 (Caspase 3), TYR-55, HIS-39, SER-49, GLU-322, GLY-326 (COX-2), SER-95, LEU-94, ARG-82, VAL-123, ALA-96 (TNF-α), ASP-414, LYS-322, GLU-326, GLU-416, GLU-438, ALA-439, GLU-437 (Cytochrome P450) and LEU-47, GLN-46, CYS-61, CYS-60, ASP-63, GLU-67, GLY-65, LEU-66 (VEGF) respectively.Conclusion: The results obtained in this research work clearly indicated the docking scores of apoptotic and Inflammatory proteins imply that kaempferitrin is an effective inhibitory compound for colon cancer.

Sodium Arsenite Inhibits Lung Fibroblast Differentiation and Pulmonary Fibrosis

Pharmacology ◽  
2019 ◽  
Vol 104 (5-6) ◽  
pp. 368-376 ◽  
Author(s):  
Hao Jiao ◽  
Jieqiong Song ◽  
Xia Sun ◽  
Dong Sun ◽  
Ming Zhong
Keyword(s):  
Pulmonary Fibrosis ◽  
Sodium Arsenite ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Lavage Fluid ◽  
Lung Fibroblast ◽  
Lung Fibroblasts ◽  
Nadph Oxidase 4 ◽  
Normal Human

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a high mortality and poor prognosis. Transforming growth factor (TGF)-β plays crucial roles in the pathogenesis of IPF. To investigate the role of sodium arsenite (SA) on fibroblast differentiation and pulmonary fibrosis, we checked the effects of SA on TGF-β-induced normal human lung fibroblasts (NHLFs) differentiation, and the anti-fibrotic effect of SA on bleomycin (BLM)-induced pulmonary fibrosis in mouse. SA treatment significantly inhibits α-smooth muscle actin and fibronectin (FN) expression in TGF-β treated NHLFs; and SA also inhibits TGF-β stimulated expression of NADPH oxidase 4 and accumulation of intracellular reactive oxygen species. TGF-β-induced the phosphorylation of ERK and Smad3 were also blocked by SA. The administration of SA (IP) suppressed BLM-induced lung fibrosis characterized as the inhibition of collagen deposition, TGF-β accumulation in bronchoalveolar lavage fluid, and the expression of FN and collagen 1a2 in lung tissue. This study revealed that SA inhibits TGF-β-induced lung fibroblast differentiation and BLM-induced pulmonary fibrosis in mice, suggesting that SA could be a potential therapeutic approach to IPF.

scholarly journals Anti-oxidant, anti-apoptotic, anti-hypoxic and anti-inflammatory conditions induced by PTY-2 against STZ-induced stress in islets

2019 ◽  
Author(s):  
Shivani Srivastava ◽  
Harsh Pandey ◽  
Surya Kumar Singh ◽  
Yamini Bhusan Tripathi
Keyword(s):  
Caspase 3 ◽  
Diabetic Control ◽  
Protective Role ◽  
Diabetic Rats ◽  
Male Rats ◽  
List Type ◽  
Pueraria Tuberosa ◽  
Glucose Levels ◽  
Inflammatory Conditions ◽  
Tnf Α

AbstractBackground and AimEarlier assessment of Pueraria tuberosa tubers has shown anti-diabetic effects through incretin mimetic action and DPP-IV inhibition. The aim of this work was to further explore the protective role of aqueous extract of Pueraria tuberosa against streptozotocin (STZ)-induced pancreatic stress in rats.MethodsDiabetes was induced with STZ (65 mg/kg body weight) in Charles foster male rats. After 60 days of STZ administration, animals with blood glucose levels > 200 g/dL were considered as diabetic. All the rats were later divided into three groups: Group-1 (STZ untreated normal rats), Group-2 (Diabetic control), and Group-3 (PTY-2 [50 mg/100 g bw treatment for next 10 days to diabetic rats). The rats were then sacrificed at the 10th day of treatment accordingly.ResultsSTZ treatment led to an increase in expression of MMP-9, Tnf α, HIF-1α, VEGF, IL-6, PKC ε, NF-kB, and Caspase-3. Reverse transcriptase Polymerase Chain Reaction (PCR), IHC and western blot analysis showed an increase in the expressions of superoxide dismutase (SOD) and Nephrin, and a decrease in the expressions of NF-kB, PKC ε, TNF-α MMP-9, HIF-1α, VEGF, Caspase 3 and IL-6 after 10 days of PTY-2 treatment.ConclusionThe results show that PTY-2 favorably changed the expression of NF-kB, PKC ε, TNF α, MMP 9, HIF-1α, VEGF, IL-6, Caspase3, Nephrin and SOD in cases of STZ-induced pancreatic stress. Further evaluation of PTY-2 might be helpful in establishing its role in the management of diabetes mellitus.HighlightsPTY 2 act as a protective herbal drug against STZ induced islet stress.PTY 2 upregulates protective and downregulates harmful markers.This study composed of four pathway through which PTY 2 acts on pancreas.GRAPHICAL ABSTRACTMechanism of action of PTY 2 against STZ induced islet stress.

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