Effects of combined administration of vitamins C and E on some Plasmodium berghei-induced pathological changes and oxidative stress in mice

Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus, may eventually leads to irreversible heart failure. Metformin is the cornerstone of diabetes therapy, especially for type 2 diabetes. Statins are widely used to reduce the risk of cardiovascular diseases. In this study, we aimed to investigate whether the combined administration of metformin and atorvastatin could achieve superior protective effects on DCM and to elucidate its molecular mechanism. Here, db/db mice (9–10 weeks old) were randomly divided into four groups, including sterile water group (DM), metformin group (MET, 200 mg/kg/day), atorvastatin group (AVS, 10 mg/kg/day), and combination therapy group (MET + AVS). Mice were treated with different drugs via gavage once per day for 3 months. After 3 months of treatment, the pathological changes (inflammation, fibrosis, hypertrophy, and oxidative stress makers) were detected by histopathological techniques, as well as Western blotting. The H9C2 cardiomyocytes were treated with palmitate (PAL) to mimic diabetic condition. The cells were divided into control group, PAL treatment group, MET + PAL treatment group, AVS + PAL treatment group, and MET + AVS + PAL treatment group. The effects of MET and AVS on the cell viability and inflammation of H9C2 cells subjected to PAL condition were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. Both MET and AVS prevented diabetes-induced fibrosis, hypertrophy, and inflammation. The combination therapy showed superior effects in protecting myocardial tissue against diabetes-induced injury. Mechanistically, the combination therapy significantly inhibited oxidative stress and the expression levels of inflammation-related proteins, e.g., NLRP3, caspase-1, interleukin-1β (IL-1β), Toll-like receptor 4 (TLR4), and P-p65/p65, in both cardiac tissues and H9C2 cells. TUNEL assay showed that the combination therapy significantly attenuated the apoptosis of cardiomyocytes; decreased the expression level of pro-apoptotic-related proteins, such as cleaved caspase-3 and BAX; and enhanced the expression level of anti-apoptotic protein (Bcl-2). Furthermore, the combination therapy remarkably upregulated the expression levels of 5′-AMP-activated protein kinase (AMPK) and SIRT1. Our findings indicated that the anti-inflammation and anti-apoptosis effects of the combination therapy may be related to activation of AMPK/SIRT1 signaling pathway.

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Effects of Polysaccharide from Malus halliana Koehne Flowers in Cyclophosphamide-Induced Immunosuppression and Oxidative Stress on Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1603735 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Yingying Niu ◽

Jing Dong ◽

Huimin Jiang ◽

Jinmei Wang ◽

Zhenhua Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Mrna Expression ◽

Mononuclear Phagocytes ◽

Pathological Changes ◽

Splenic Lymphocytes ◽

Immunomodulatory Effects ◽

Spleen Tissue ◽

Carbon Clearance ◽

Immune Capacity ◽

And Oxidative Stress

The immunomodulatory effects of Malus halliana flower polysaccharide (MHFP) were investigated in this paper. The model of immunosuppressive mice was established by cyclophosphamide, which was treated with different dosages of MHFP (600, 400, and 200 mg/kg·d-1). The results showed that MHFP significantly increased the index of the spleen and thymus and improved the atrophy of immune organs. MHFP enhanced the ability of carbon clearance and phagocytosis of mononuclear phagocytes in mice. Meanwhile, MHFP promoted the proliferation of splenic lymphocytes. MHFP could enhance the content of serum hemolysin and improve the decrease of hemolysin induced by cyclophosphamide. The contents of ACP and LDH in the serum and spleen were determined, indicating that MHFP could enhance the activity of macrophages. MHFP promoted the content of cytokines (IL-2, IL-6, TNF-α, and IFN-γ) and mRNA expression. At the same time, the pathological changes of the spleen tissue also showed that MHFP could improve the immunosuppression induced by cyclophosphamide. In addition, MHFP increased the content of SOD, T-AOC, and CAT in the serum and spleen tissue, decreased the level of MDA, and improved the oxidative stress caused by cyclophosphamide. In conclusion, MHFP could effectively improve the immunosuppression and oxidative stress induced by cyclophosphamide and enhance the immune capacity of mice.

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Co-administration of Colchicine and Allopurinol alleviates vascular calcification induced by hyperuricemia via suppressing inflammation and oxidative stress

Archives of Medical Science ◽

10.5114/aoms/127037 ◽

2021 ◽

Author(s):

Yang Ji ◽

Maojing Wang ◽

Libo Sun ◽

Wei Ding ◽

Shanglang Cai ◽

...

Keyword(s):

Oxidative Stress ◽

Vascular Calcification ◽

Inflammatory Responses ◽

Combined Treatment ◽

Cellular Models ◽

Expression Of Genes ◽

Combined Administration ◽

Single Compound ◽

Novel Therapeutic Strategies ◽

And Oxidative Stress

IntroductionOxidative stress and inflammation are involved in the pathogenesis of VC in patients with hyperuricemia, while lowering the uric acid level accordingly reduces the risk of VC. Additionally, both ALL and COL suppress inflammatory response and oxidative stress. However, it is unclear whether novel therapeutic strategies, such as combined administration of COL and ALL, can achieve a better performance in lowering hyperuricemia. Therefore, we aimed to investigate the effect of co-administration of COL and ALL in the treatment of VC.Material and methodsVon Kossa staining was performed to evaluate the aortic vascular calcification in HUC rats treated under different therapeutic conditions. Quantitative real-time PCR was carried out to analyze the expression of genes involved in the pathogenesis of hyperuricemia.ResultsCombined administration of COL and ALL alleviated the aortic vascular calcification in HUC rats. The aberrant up-regulation of genes related to differentiation, BMP2, RUNX2, OC and ALP, was effectively reversed by the combined treatment of COL and ALL in HUC rats and cellular models. Besides, the dysregulation of enzymes and cytokines involved in oxidative and inflammatory responses was restored by the combined treatment of COL and ALL.ConclusionsIn this study, we tested the therapeutic effect of ALL combined with COL on the treatment of VC in animals with hyperuricemia by examining their influence on oxidative stress and inflammation. Our work helped to gain a deeper insight into the molecular mechanism of hyperuricemia, and revealed that the efficiency of the combined treatment with COL and ALL out-performed the mono-therapy of any single compound.

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Effects of dietary vitamin E deficiency on systematic pathological changes and oxidative stress in fish

Oncotarget ◽

10.18632/oncotarget.13729 ◽

2016 ◽

Vol 7 (51) ◽

pp. 83869-83879 ◽

Cited By ~ 2

Author(s):

Kaiyu Wang ◽

Erlong Wang ◽

Zhenyang Qin ◽

Zhen Zhou ◽

Yi Geng ◽

...

Keyword(s):

Oxidative Stress ◽

Vitamin E ◽

Dietary Vitamin ◽

Pathological Changes ◽

Vitamin E Deficiency ◽

And Oxidative Stress

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Future Therapies in PAH: Update on the New Landscape and Drugs in the Pipeline

Advances in Pulmonary Hypertension ◽

10.21693/1933-088x-13.2.76 ◽

2014 ◽

Vol 13 (2) ◽

pp. 76-80 ◽

Cited By ~ 2

Author(s):

Ioana R. Preston

Keyword(s):

Oxidative Stress ◽

Vascular Remodeling ◽

Trial Design ◽

Pathological Changes ◽

Pulmonary Vascular Remodeling ◽

The Past ◽

Therapeutic Landscape ◽

Pulmonary Arterial ◽

New Compounds ◽

And Oxidative Stress

Research in pulmonary hypertension (PH) in general and in pulmonary arterial hypertension (PAH) in particular has been extremely active in the past few years. The current therapeutic landscape includes multiple compounds shown to be active in modulating and ameliorating the pathological changes in the endothelin, nitric oxide (NO), and prostacyclin pathways. In addition, development of new compounds targeting pathways of pulmonary vascular remodeling due to inflammation, fibrosis, and oxidative stress is underway. This review summarizes the most recent achievements and newly conducted clinical trials—some with novel trial design—for treatment of PH and PAH.

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PI3K/AKT/mTOR Signalling Inhibitor Chrysophanol Ameliorates Neurobehavioural and Neurochemical Defects in Propionic Acid-induced Experimental Model of Autism

10.21203/rs.3.rs-705335/v1 ◽

2021 ◽

Author(s):

Aarti Sharma ◽

Sidharth Mehan

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Blood Plasma ◽

Rat Brain ◽

Forced Swim Test ◽

Brain Homogenate ◽

Autism Spectrum ◽

Pathological Changes ◽

And Oxidative Stress ◽

Mtor Signalling

Abstract Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social-communication deficits and repetitive behaviour. Several studies have revealed that overactivation of the PI3K/AKT/mTOR signalling pathways during brain development plays an important role in the pathogenesis of autism. The PI3K/AKT/mTOR signalling pathway overexpression produces neurological abnormalities by increasing cell death, neuroinflammation, and oxidative stress. Chrysophanol, also known as chrysophanic acid, is a natural substance derived from the plant Rheum palmatum, a well-known Chinese herbal remedy with potential pharmacological applications. The purpose of this study was to look into the neuroprotective effect of CPH on neurobehavioral, molecular, neurochemical, and gross pathological changes in ICV-PPA-induced autism-like rats, with a particular emphasis on its effect on PI3K/AKT/mTOR downregulation in the brain. Furthermore, we looked at how CPH affected the levels of myelin basic protein (MBP) in rat brain homogenate, as well as apoptotic markers such caspase-3, Bax, and Bcl-2 levels in rat brain homogenate and blood plasma samples. Rats were examined for behavioural abnormalities, like neuromuscular dysfunction using actophotometer, motor coordination by beam crossing task (BCT), depressive behaviour with forced swim test (FST), cognitive deficit, and consolidation of memory using Morris water maze (MWM) task. Prolonged oral CPH administration from day 12 to day 44 of the experimental schedule reduces autistic-like symptoms in PPA-treated rats. In addition, cellular, molecular, cell death markers, neuroinflammatory cytokines, neurotransmitter levels, and oxidative stress indicators have been examined in rat brain homogenates, blood plasma, and CSF samples. The current findings suggest that CPH also restores the altered neurochemical levels and potentially prevents autism-like gross pathological changes, including demyelination volume in the rat brain.

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Late-stage systemic immune effectors in Plasmodium berghei ANKA infection: biopterin and oxidative stress

Pteridines ◽

10.1515/pterid-2014-0019 ◽

2015 ◽

Vol 26 (3) ◽

pp. 105-112

Author(s):

Funda Dogruman-Al ◽

Ayşe Başak Engin ◽

Neslihan Bukan ◽

Seda Evirgen-Bostanci ◽

Kemal Çeber

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Plasmodium Berghei ◽

Post Inoculation ◽

Plasmodium Berghei Anka ◽

Systemic Oxidative Stress ◽

Redox Active ◽

Induce Lipid Peroxidation ◽

And Oxidative Stress ◽

Gpx Activity

AbstractTo investigate the involvement of systemic oxidative stress in the pathogenesis of murine cerebral malaria, mice were infected with the Plasmodium berghei (P. berghei) ANKA 6653 strain. Serum tryptophan (Trp), kynurenine and urinary biopterin, liver, brain, spleen and serum superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) and nitrite and nitrate (NOx) levels were measured on day 7 post-inoculation. Our data showed a significant decrease in SOD and an increase in GPx activity and MDA level in all the examined biological materials (p<0.05), except spleen. Conversely, GPx activities in spleen were depleted, while SOD and MDA levels remained unchanged. Increased MDA levels might indicate increased peroxynitrite production, lipid peroxidation and oxidative stress. Also, elevated urinary biopterin, which was accompanied by increased NOx (p<0.05), may support the inhibition of Trp degradation (p>0.05). The excessive NO synthesis in P. berghei infection may be related to the up-regulation of inducible NO synthase, which was in accordance with the increased biopterin excretion. Thus, the large quantities of released toxic redox active radicals attack cell membranes and induce lipid peroxidation. Although P. berghei infection did not demonstrate systemic Trp degradation and related indoleamine-2,3-dioxygenase activity, it may cause multi-organ failure and death, owing to host-derived severe oxidative stress.

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