scholarly journals Intratracheally Inhalable Nifedipine-Loaded Chitosan-PLGA Nanocomposites as a Promising Nanoplatform for Lung Targeting: Snowballed Protection via Regulation of TGF-β/β-Catenin Pathway in Bleomycin-Induced Pulmonary Fibrosis

2021 ◽  
Vol 14 (12) ◽  
pp. 1225
Author(s):  
Mohammed H. Elkomy ◽  
Rasha A. Khallaf ◽  
Mohamed O. Mahmoud ◽  
Raghda R. S. Hussein ◽  
Asmaa M. El-Kalaawy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Fibrosis ◽  
Intratracheal Instillation ◽  
Entrapment Efficiency ◽  
Pharmacokinetic Studies ◽  
Channel Blockers ◽  
Systemic Bioavailability ◽  
High Entrapment Efficiency ◽  
And Oxidative Stress

Pulmonary fibrosis is a serious ailment that may progress to lung remodeling and demolition, where the key participants in its incidence are fibroblasts responding to growth factors and cellular calcium swinging. Calcium channel blockers, like nifedipine (NFD), may represent auspicious agents in pulmonary fibrosis treatment. Unfortunately, NFD bears complicated pharmacodynamics and a diminished systemic bioavailability. Thus, the current study aimed to develop a novel, non-invasive nanoplatform for NFD for direct/effective pulmonary targeting via intratracheal instillation. A modified solvent emulsification–evaporation method was adopted for the fabrication of NFD-nanocomposites, integrating poly(D,L-lactide-co-glycolide) (PLGA), chitosan (CTS), and polyvinyl alcohol, and optimized for different physiochemical properties according to the 32 full factorial design. Additionally, the aerodynamic behavior of the nanocomposites was scrutinized through cascade impaction. Moreover, the pharmacokinetic investigations were conducted in rats. Furthermore, the optimum formulation was tested in bleomycin-induced pulmonary fibrosis in rats, wherein fibrotic and oxidative stress parameters were measured. The optimum nanocomposites disclosed a nanosized spherical morphology (226.46 nm), a high entrapment efficiency (61.81%) and a sustained release profile over 24 h (50.4%). As well, it displayed a boosted in vitro lung deposition performance with a mass median aerodynamic diameter of 1.12 µm. Pharmacokinetic studies manifested snowballed bioavailability of the optimal nanocomposites by 3.68- and 2.36-fold compared to both the oral and intratracheal suspensions, respectively. The intratracheal nanocomposites revealed a significant reduction in lung fibrotic and oxidative stress markers notably analogous to normal control besides repairing abnormality in TGF-β/β-catenin pathway. Our results conferred a compelling proof-of-principle that NFD-CTS-PLGA nanocomposites can function as a promising nanoparadigm for pulmonary fibrosis management.

scholarly journals CoQ10 Enhances the Efficacy of Airway Basal Stem Cell Transplantation on Bleomycin-induced Idiopathic Pulmonary Fibrosis in Mice

2021 ◽  
Author(s):  
Huanbin Liu ◽  
Yidi Zhang ◽  
Jinjun Jiang ◽  
Yulong Luo ◽  
Jingxin Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Pulmonary Inflammation ◽  
Intratracheal Instillation ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Induced Apoptosis ◽  
Lung Regeneration

Abstract Background: Recent studies have demonstrated that airway basal stem cells (BCs) transplantation can ameliorate bleomycin-induced idiopathic pulmonary fibrosis (IPF) through lung regeneration promotion. However, BCs under oxidative stress in the alveolar microenvironment are poor in survival, causing unsatisfied efficacy of BCs transplantation. In this study, we investigated whether Coenzyme Q10(CoQ10) counteracts oxidative stress in the alveolar microenvironment, thus improved the efficacy of BCs transplantation for IPF treatment.Methods: The protective effects of CoQ10 on H2O2-induced BCs apoptosis and cytoplasmic reactive oxygen species (ROS) level were tested by flow cytometry in vitro. The therapeutic effects of BCs combined with CoQ10 were compared to a single BCs transplantation protocol in IPF treatment after two weeks and were evaluated by parameters including changes of body weight and survival rate, as well as various levels of pulmonary inflammation, α-SMA expression and hydroxyproline (HYP) in IPF mice lung tissues.Results: CoQ 10 preincubation with BCs (10 mM, 24 h) significantly reduced the late apoptosis of BCs and the number of oxidative stressful BCs as a result of H2O2 stimulation (1mM, 6h) in vitro. IPF mice models were constructed through bleomycin (5 mg/Kg) intratracheal instillation. Bleomycin-induced IPF mice showed weight loss continuously and mortality increased progressively during modeling. Serious pulmonary inflammatory cell infiltration, collagen fiber proliferation, and collagen protein deposition were observed in lung tissues of IPF mice. Though BCs transplantation alone improved indicators above in bleomycin-induced IPF mice to some extent, the combination with CoQ10 improved the transplantation efficacy and obtained better therapeutic effects.Conclusion：CoQ10 blocked H2O2-induced apoptosis of BCs and ROS production in vitro, and enhanced the efficacy of BCs transplantation on bleomycin-induced IPF in mice.

scholarly journals Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 507
Author(s):  
Rosaria Meccariello ◽  
Stefania D’Angelo
Keyword(s):  
Oxidative Stress ◽  
Food Sources ◽  
Preventive Action ◽  
Nutritional Interventions ◽  
Beneficial Effects ◽  
Age Related ◽  
Macromolecular Damage ◽  
And Oxidative Stress

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.

Pirfenidone mediates cigarette smoke extract induced inflammation and oxidative stress in vitro and in vivo

2021 ◽  
Vol 96 ◽  
pp. 107593
Author(s):  
Yiming Ma ◽  
Lijuan Luo ◽  
Xiangming Liu ◽  
Herui Li ◽  
Zihang Zeng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Cigarette Smoke Extract ◽  
And Oxidative Stress

In vitro study on the effects of iron sucrose, ferric gluconate and iron dextran on redox-active iron and oxidative stress

2011 ◽  
Vol 60 (07) ◽  
pp. 459-465
Author(s):  
Brigitte Sturm ◽  
Hannes Steinkellner ◽  
Nina Ternes ◽  
Hans Goldenberg ◽  
Barbara Scheiber-Mojdehkar
Keyword(s):  
Oxidative Stress ◽  
In Vitro Study ◽  
Iron Sucrose ◽  
Vitro Study ◽  
Iron Dextran ◽  
Active Iron ◽  
Redox Active ◽  
And Oxidative Stress

The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2)

2016 ◽  
Vol 35 (12) ◽  
pp. 1252-1263 ◽  
Author(s):  
SS Palabiyik ◽  
E Karakus ◽  
Z Halici ◽  
E Cadirci ◽  
Y Bayir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Folk Medicine ◽  
Hepatoprotective Activity ◽  
High Dose ◽  
Protective Effects ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

Enhanced oral bioavailability of nisoldipine-piperine-loaded poly-lactic-co-glycolic acid nanoparticles

2017 ◽  
Vol 6 (6) ◽  
pp. 517-526 ◽  
Author(s):  
Permender Rathee ◽  
Anjoo Kamboj ◽  
Shabir Sidhu
Keyword(s):  
Oral Bioavailability ◽  
Drug Loading ◽  
Average Particle Size ◽  
Entrapment Efficiency ◽  
Pharmacokinetic Interaction ◽  
Precipitation Method ◽  
Pharmacokinetic Studies ◽  
Average Particle

AbstractBackground:Piperine helps in the improvement of bioavailability through pharmacokinetic interaction by modulating metabolism when administered with other drugs. Nisoldipine is a substrate for cytochrome P4503A4 enzymes. The study was undertaken to assess the influence of piperine on the pharmacokinetics and pharmacodynamics of nisoldipine nanoparticles in rats.Methods:Optimization studies of nanoparticles were performed using Taguchi L9 orthogonal array, and the nanoparticles were formulated by the precipitation method. The influence of piperine and nanoparticles was evaluated by means of in vivo kinetic and dynamic studies by oral administration in rats.Results:The entrapment efficiency, drug loading, ζ potential, and average particle size of optimized nisoldipine-piperine nanoparticles was 89.77±1.06%, 13.6±0.56%, −26.5 mV, and 132±7.21 nm, respectively. The in vitro release in 0.1 n HCl and 6.8 pH phosphate buffer was 96.9±0.48% and 98.3±0.26%, respectively. Pharmacokinetic studies showed a 4.9-fold increase in oral bioavailability and a >28.376±1.32% reduction in systemic blood pressure by using nanoparticles as compared to control (nisoldipine suspension) in Wistar rats.Conclusion:The results revealed that piperine being an inhibitor of cytochrome P4503A4 enzymes enhanced the bioavailability of nisoldipine by 4.9-fold in nanoparticles.

Evidence of Autophagy Gene and Protein Expression Response to Heat and Oxidative Stress in Avian Muscle Cells: In Vivo and in Vitro Studies.

2014 ◽  
Vol 76 ◽  
pp. S72
Author(s):  
Sami Dridi ◽  
Alissa Piekarski ◽  
Kentu Lassiter ◽  
Elizabeth Greene ◽  
Nick Anthony ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Muscle Cells ◽  
Autophagy Gene ◽  
Avian Muscle ◽  
Gene And Protein Expression ◽  
Expression Response ◽  
And Oxidative Stress

scholarly journals Coenzyme Q10, Ageing and the Nervous System: An Overview

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 2
Author(s):  
David Mantle ◽  
Robert A. Heaton ◽  
Iain P. Hargreaves
Keyword(s):  
Oxidative Stress ◽  
Coenzyme Q10 ◽  
Neurological Disorders ◽  
Neurological Disease ◽  
Age Related ◽  
Increased Risk ◽  
Potential Therapeutic Role ◽  
Ageing Brain ◽  
And Oxidative Stress

The ageing brain is characterised by changes at the physical, histological, biochemical and physiological levels. This ageing process is associated with an increased risk of developing a number of neurological disorders, notably Alzheimer’s disease and Parkinson’s disease. There is evidence that mitochondrial dysfunction and oxidative stress play a key role in the pathogenesis of such disorders. In this article, we review the potential therapeutic role in these age-related neurological disorders of supplementary coenzyme Q10, a vitamin-like substance of vital importance for normal mitochondrial function and as an antioxidant. This review is concerned primarily with studies in humans rather than in vitro studies or studies in animal models of neurological disease. In particular, the reasons why the outcomes of clinical trials supplementing coenzyme Q10 in these neurological disorders is discussed.

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