scholarly journals Antioxidative 1,4-Dihydropyridine Derivatives Modulate Oxidative Stress and Growth of Human Osteoblast-Like Cells In Vitro

Antioxidants ◽  
2018 ◽  
Vol 7 (9) ◽  
pp. 123 ◽  
Author(s):  
Lidija Milkovic ◽  
Tea Vukovic ◽  
Neven Zarkovic ◽  
Franz Tatzber ◽  
Egils Bisenieks ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Growth ◽  
Cell Model ◽  
Second Messengers ◽  
Human Osteoblast ◽  
Tert Butyl Hydroperoxide ◽  
Human Stress ◽  
Set Up ◽  
Dihydropyridine Derivatives

Oxidative stress has been implicated in pathophysiology of different human stress- and age-associated disorders, including osteoporosis for which antioxidants could be considered as therapeutic remedies as was suggested recently. The 1,4-dihydropyridine (DHP) derivatives are known for their pleiotropic activity, with some also acting as antioxidants. To find compounds with potential antioxidative activity, a group of 27 structurally diverse DHPs, as well as one pyridine compound, were studied. A group of 11 DHPs with 10-fold higher antioxidative potential than of uric acid, were further tested in cell model of human osteoblast-like cells. Short-term combined effects of DHPs and 50 µM H2O2 (1-h each), revealed better antioxidative potential of DHPs if administered before a stressor. Indirect 24-h effect of DHPs was evaluated in cells further exposed to mild oxidative stress conditions induced either by H2O2 or tert-butyl hydroperoxide (both 50 µM). Cell growth (viability and proliferation), generation of ROS and intracellular glutathione concentration were evaluated. The promotion of cell growth was highly dependent on the concentrations of DHPs used, type of stressor applied and treatment set-up. Thiocarbatone III-1, E2-134-1 III-4, Carbatone II-1, AV-153 IV-1, and Diethone I could be considered as therapeutic agents for osteoporosis although further research is needed to elucidate their bioactivity mechanisms, in particular in respect to signaling pathways involving 4-hydroxynoneal and related second messengers of free radicals.

scholarly journals Phytochemicals from the Cocoa Shell Modulate Mitochondrial Function, Lipid and Glucose Metabolism in Hepatocytes via Activation of FGF21/ERK, AKT, and mTOR Pathways

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 136
Author(s):  
Miguel Rebollo-Hernanz ◽  
Yolanda Aguilera ◽  
Maria A. Martin-Cabrejas ◽  
Elvira Gonzalez de Gonzalez de Mejia
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthase ◽  
Cell Model ◽  
Fibroblast Growth Factor 21 ◽  
Alcoholic Fatty Liver ◽  
Atp Production ◽  
Cocoa Shell

The cocoa shell is a by-product that may be revalorized as a source of bioactive compounds to prevent chronic cardiometabolic diseases. This study aimed to investigate the phytochemicals from the cocoa shell as targeted compounds for activating fibroblast growth factor 21 (FGF21) signaling and regulating non-alcoholic fatty liver disease (NAFLD)-related biomarkers linked to oxidative stress, mitochondrial function, and metabolism in hepatocytes. HepG2 cells treated with palmitic acid (PA, 500 µmol L−1) were used in an NAFLD cell model. Phytochemicals from the cocoa shell (50 µmol L−1) and an aqueous extract (CAE, 100 µg mL−1) enhanced ERK1/2 phosphorylation (1.7- to 3.3-fold) and FGF21 release (1.4- to 3.4-fold) via PPARα activation. Oxidative stress markers were reduced though Nrf-2 regulation. Mitochondrial function (mitochondrial respiration and ATP production) was protected by the PGC-1α pathway modulation. Cocoa shell phytochemicals reduced lipid accumulation (53–115%) and fatty acid synthase activity (59–93%) and prompted CPT-1 activity. Glucose uptake and glucokinase activity were enhanced, whereas glucose production and phosphoenolpyruvate carboxykinase activity were diminished. The increase in the phosphorylation of the insulin receptor, AKT, AMPKα, mTOR, and ERK1/2 conduced to the regulation of hepatic mitochondrial function and energy metabolism. For the first time, the cocoa shell phytochemicals are proved to modulate FGF21 signaling. Results demonstrate the in vitro preventive effect of the phytochemicals from the cocoa shell on NAFLD.

Feasibility of Using Vitamin E-Loaded Poly(ε-caprolactone)/Gelatin Nanofibrous Mat to Prevent Oxidative Stress in Skin

2020 ◽  
Vol 20 (6) ◽  
pp. 3554-3562 ◽  
Author(s):  
Saba Kalantary ◽  
Farideh Golbabaei ◽  
Masoud Latifi ◽  
Mohammad Ali Shokrgozar ◽  
Mehdi Yaseri
Keyword(s):  
Oxidative Stress ◽  
Vitamin E ◽  
Electrical Potential ◽  
Radical Scavenging ◽  
Occupational Exposures ◽  
Skin Cells ◽  
Novel Approach ◽  
Tert Butyl Hydroperoxide ◽  
Increased Risk

Some occupational skin exposures lead to the formation of reactive oxygen species (ROS). The occupational exposure of workers to ROS has been found to be associated with an increased risk of developing skin injuries; therefore, it is essential to protect skin against ROS formation. Recently, some studies have been conducted on introducing better alternatives for skin protection. Nanofibers are good candidates for this purpose. The current study was carried out to assess vitamin E-loaded hybrid Poly(ε-caprolactone) (PCL)/gelatin (Gt) nanofibres mats as protective layers of skin exposed to occupational exposures. Vitamin E (VE) was successfully incorporated into PCL/Gt nanofibers while they were formed by electrospinning method. Nanofibers mats were characterized using scanning electron microscopy (SEM) and fourier transform infrared spectroscopy (FTIR). Their degradation behavior, in vitro release, biocompatibility, and antioxidant activity were studied. The diameters of the PCL/Gt/VE nanofibers decreased with the addition of vitamin E. The degradation rate of nanofibers was equal to 42.98 and 50.69% during 7 and 14 days, respectively. Nanofibers containing vitamin E showed an initial burst followed by a sustained release. The PCL/Gt/VE nanofibers exhibited good free radical scavenging activities despite being exposed to a high electrical potential during electrospinning. PCL/Gt/VE nanofibers supported a higher level of viability compared to PCL/Gt ones and significantly assisted human skin cells against tert-Butyl hydroperoxide (t-BHP) induced oxidative stress. Overall, PCL/Gt/VE nanofibers can potentially be used to protect skin against oxidative stress as a novel approach for worker’s healthcare.

Electrosprayed Nanoapatite: A New Generation of Bioactive Material

2007 ◽  
Vol 361-363 ◽  
pp. 597-600 ◽  
Author(s):  
E.S. Thian ◽  
Z. Ahmad ◽  
Jie Huang ◽  
Mohan J. Edirisinghe ◽  
S.N. Jayasinghe ◽  
...  
Keyword(s):  
Cell Growth ◽  
Simulated Body Fluid ◽  
Body Fluid ◽  
Human Osteoblast ◽  
Considerable Potential ◽  
Bioactive Material ◽  
Time Points ◽  
Glass Substrates ◽  
New Generation

Fine nanoapatite relics were deposited on glass substrates by electrohydrodynamic atomisation, using nanohydroxyapatite (nHA), nano-carbonated hydroxyapatite (nCHA) and nanosilicon- substituted hydroxyapatite (nSiHA) suspensions. These electrosprayed nanoapatites were evaluated in-vitro using simulated body fluid (SBF) and human osteoblast (HOB) cells. The SBF study revealed that newly-formed apatite layers were observed on the surface of the relics. Furthermore, enhanced HOB cell growth was observed on each of the nanoapatites at all time points. Hence, this work demonstrated that electrosprayed nanoapatites offer considerable potential as biomaterials.

scholarly journals TSH Combined with TSHR Aggravates Diabetic Peripheral Neuropathy by Promoting Oxidative Stress and Apoptosis in Schwann Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Jingwen Fan ◽  
Qi Pan ◽  
Qun Gao ◽  
Wenqing Li ◽  
Fei Xiao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Peripheral Neuropathy ◽  
Diabetic Peripheral Neuropathy ◽  
Cell Model ◽  
Cell Damage ◽  
Motor Nerve ◽  
Thyroid Stimulating Hormone ◽  
Motor Nerve Conduction Velocity ◽  
The Impact

Subclinical hypothyroidism (SCH) is associated with diabetic peripheral neuropathy (DPN); however, the mechanism underlying this association remains unknown. This study is aimed at examining neurofunctional and histopathological alterations in a type 2 diabetes (T2DM) mouse model of SCH and investigating the impact of thyroid-stimulating hormone (TSH) in an in vitro DPN cell model established using RSC96 cells under high glucose (HG) and palmitic acid (PA) stimulation. Our results indicated that T2DM, in combination with SCH, aggravated abnormal glucose and lipid metabolism in T2DM and dramatically destroyed the peripheral nervous system by increasing paw withdrawal latency, decreasing motor nerve conduction velocity, and exacerbating ultrastructural deterioration of the damaged sciatic nerve caused by diabetes. Furthermore, the results of our in vitro experiments showed that TSH intensified HG/PA-induced RSC96 cell damage by inducing oxidative stress, mitochondrial dysfunction, and apoptosis. More importantly, TSHR knockout or inhibition of PA-induced TSHR palmitoylation could alleviate the apoptosis induced by TSH. Overall, in this study, the novel mechanisms by which TSH, as an independent risk factor for DPN progression, aggravating Schwann cell apoptosis and demyelination, are elucidated. These findings indicate that TSHR could be a potential target for both the prevention and treatment of DPN and, possibly, other microvascular diseases, and have implication in the clinical management of patients with DPN.

scholarly journals Intracellular cyclic AMP levels modulate differential adaptive responses on epimastigotes and cell culture trypomastigotes of Trypanosoma cruzi

2019 ◽  
Author(s):  
Tamara Sternlieb ◽  
Alejandra C. Schoijet ◽  
Guillermo D. Alonso
Keyword(s):  
Oxidative Stress ◽  
Trypanosoma Cruzi ◽  
Second Messengers ◽  
Redox Status ◽  
Adaptive Responses ◽  
Cellular Processes ◽  
The Many ◽  
Hemoglobin Degradation ◽  
Intracellular Second Messengers

ABSTRACTAmong the many environmental challenges the parasite Trypanosoma cruzi has to overcome to complete its life cycle through different hosts, oxidative stress plays a central role. Different stages of this parasite encounter distinct sources of oxidative stress, such as the oxidative burst of the immune system, or the Heme released from hemoglobin degradation in the triatomine’s midgut. Also, the redox status of the surroundings functions as a signal to the parasite, triggering processes coupled to differentiation or proliferation. Intracellular second messengers, like cAMP, are responsible for the transduction of environmental queues and initiating cellular processes accordingly. In trypanosomatids cAMP is involved in a variety of processes, including proliferation, differentiation, osmoregulation and quorum sensing. Trypanosomatid phosphodiesterases (PDE) show atypical pharmacological properties and some have been involved in key processes for the survival of the parasites, which validates them as attractive therapeutic targets. Our work here shows that cAMP modulates different processes according to parasite stage. Epimastigotes become more resistant to oxidative stress when pre-treated with cAMP analogs, while trypomastigotes do not alter their response to oxidative stress under the same treatment. However, cAMP analogs do increase trypomastigotes infectivity in vitro. Also, we show that TcrPDEA1, a functionally enigmatic phosphodiesterase with very high Km, is involved in the epimastigotes response to oxidative stress.

scholarly journals The Zebrafish Embryo as a Model to Test Protective Effects of Food Antioxidant Compounds

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5786
Author(s):  
Cristina Arteaga ◽  
Nuria Boix ◽  
Elisabet Teixido ◽  
Fernanda Marizande ◽  
Santiago Cadena ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Zebrafish Embryo ◽  
In Vitro Assays ◽  
Antioxidant Compounds ◽  
Protective Effects ◽  
Tert Butyl Hydroperoxide ◽  
In Vivo Effects ◽  
Β Carotene

The antioxidant activity of food compounds is one of the properties generating the most interest, due to its health benefits and correlation with the prevention of chronic disease. This activity is usually measured using in vitro assays, which cannot predict in vivo effects or mechanisms of action. The objective of this study was to evaluate the in vivo protective effects of six phenolic compounds (naringenin, apigenin, rutin, oleuropein, chlorogenic acid, and curcumin) and three carotenoids (lycopene B, β-carotene, and astaxanthin) naturally present in foods using a zebrafish embryo model. The zebrafish embryo was pretreated with each of the nine antioxidant compounds and then exposed to tert-butyl hydroperoxide (tBOOH), a known inducer of oxidative stress in zebrafish. Significant differences were determined by comparing the concentration-response of the tBOOH induced lethality and dysmorphogenesis against the pretreated embryos with the antioxidant compounds. A protective effect of each compound, except β-carotene, against oxidative-stress-induced lethality was found. Furthermore, apigenin, rutin, and curcumin also showed protective effects against dysmorphogenesis. On the other hand, β-carotene exhibited increased lethality and dysmorphogenesis compared to the tBOOH treatment alone.

Mechanical forces and their second messengers in stimulating cell growth in vitro

1992 ◽  
Vol 262 (3) ◽  
pp. R350-R355 ◽  
Author(s):  
H. H. Vandenburgh
Keyword(s):  
Cell Growth ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Second Messengers ◽  
Second Messenger ◽  
Model Systems ◽  
Mechanical Forces ◽  
Unicellular Organisms ◽  
Multicellular Organisms

Mechanical forces play an important role in modulating the growth of a number of different tissues including skeletal muscle, smooth muscle, cardiac muscle, bone, endothelium, epithelium, and lung. As interest increases in the molecular mechanisms by which mechanical forces are transduced into growth alterations, model systems are being developed to study these processes in tissue culture. This paper reviews the current methods available for mechanically stimulating tissue cultured cells. It then outlines some of the putative “mechanogenic” second messengers involved in altering cell growth. Not surprisingly, many mechanogenic second messengers are the same as those involved in growth factor-induced cell growth. It is hypothesized that from an evolutionary standpoint, some second messenger systems may have initially evolved for unicellular organisms to respond to physical forces such as gravity and mechanical perturbation in their environment. As multicellular organisms came into existence, they appropriated these mechanogenic second messenger cascades for cellular regulation by growth factors.

scholarly journals Glutathione S-Transferase pi-1 Knockdown Reduces Pancreatic Ductal Adenocarcinoma Growth by Activating Oxidative Stress Response Pathways

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1501
Author(s):  
Rahul R. Singh ◽  
Jiyan Mohammad ◽  
Megan Orr ◽  
Katie M. Reindl
Keyword(s):  
Oxidative Stress ◽  
Cell Growth ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Cycle Progression ◽  
Map Kinases ◽  
Ductal Adenocarcinoma ◽  
Glutathione S Transferase ◽  
Pdac Cell ◽  
Ki 67

Glutathione S-transferase pi-1 (GSTP1) plays an important role in regulating oxidative stress by conjugating glutathione to electrophiles. GSTP1 is overexpressed in breast, colon, lung, and prostate tumors, where it contributes to tumor progression and drug resistance; however, the role of GSTP1 in pancreatic ductal adenocarcinoma (PDAC) is not well understood. Using shRNA, we knocked down GSTP1 expression in three different PDAC cell lines and determined the effect on cell proliferation, cell cycle progression, and reactive oxygen species (ROS) levels. Our results show GSTP1 knockdown reduces PDAC cell growth, prolongs the G0/G1 phase, and elevates ROS in PDAC cells. Furthermore, GSTP1 knockdown results in the increased phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun and the decreased phosphorylation of extracellular signal-regulated kinase (ERK), p65, the reduced expression of specificity protein 1 (Sp1), and the increased expression of apoptosis-promoting genes. The addition of the antioxidant glutathione restored cell viability and returned protein expression levels to those found in control cells. Collectively, these data support the working hypothesis that the loss of GSTP1 elevates oxidative stress, which alters mitogen-activated protein (MAP) kinases and NF-κB signaling, and induces apoptosis. In support of these in vitro data, nude mice bearing orthotopically implanted GSTP1-knockdown PDAC cells showed an impressive reduction in the size and weight of tumors compared to the controls. Additionally, we observed reduced levels of Ki-67 and increased expression of cleaved caspase-3 in GSTP1-knockdown tumors, suggesting GSTP1 knockdown impedes proliferation and upregulates apoptosis in PDAC cells. Together, these results indicate that GSTP1 plays a significant role in PDAC cell growth and provides support for the pursuit of GSTP1 inhibitors as therapeutic agents for PDAC.

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