scholarly journals Novel Anticancer Platinum(IV) Complexes with Adamantylamine: Their Efficiency and Innovative Chemotherapy Strategies Modifying Lipid Metabolism

2008 ◽  
Vol 2008 ◽  
pp. 1-15 ◽  
Author(s):  
Alois Kozubík ◽  
Alena Vaculová ◽  
Karel Souček ◽  
Jan Vondráček ◽  
Jaroslav Turánek ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Platinum Complexes ◽  
The Other ◽  
Stress Signaling ◽  
Cell Death Pathway ◽  
Cellular Lipids ◽  
In Vivo Effects

The impressive impact of cisplatin on cancer on one side and severe side effects, as well as the development of drug resistance during treatment on the other side, were the factors motivating scientists to design and synthesize new more potent analogues lacking disadvantages of cisplatin. Platinum(IV) complexes represent one of the perspective groups of platinum-based drugs. In this review, we summarize recent findings on both in vitro and in vivo effects of platinum(IV) complexes with adamantylamine. Based on a literary overview of the mechanisms of activity of platinum-based cytostatics, we discuss opportunities for modulating the effects of novel platinum complexes through interactions with apoptotic signaling pathways and with cellular lipids, including modulations of the mitochondrial cell death pathway, oxidative stress, signaling of death ligands, lipid metabolism/signaling, or intercellular communication. These approaches might significantly enhance the efficacy of both novel and established platinum-based cytostatics.

scholarly journals Evidence that α-Calcitonin Gene-Related Peptide Is a Neurohormone that Controls Systemic Lipid Availability and Utilization

Endocrinology ◽  
2007 ◽  
Vol 149 (1) ◽  
pp. 154-160 ◽  
Author(s):  
Rachel N. Danaher ◽  
Kerry M. Loomes ◽  
Bridget L. Leonard ◽  
Lynda Whiting ◽  
Debbie L. Hay ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Physiological Role ◽  
Calcitonin Gene Related Peptide ◽  
Physiological Regulation ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Motor Nerves ◽  
In Vivo Effects

α-Calcitonin gene-related peptide (αCGRP) is released mainly from sensory and motor nerves in response to physiological stimuli. Despite well-documented pharmacological effects, its primary physiological role has thus far remained obscure. Increased lipid content, particularly in skeletal muscle and liver, is strongly implicated in the pathogenesis of insulin resistance, but the physiological regulation of organ lipid is imperfectly understood. Here we report our systematic investigations of the effects of αCGRP on in vitro and in vivo indices of lipid metabolism. In rodents, levels of αCGRP similar to those in the blood markedly stimulated fatty acid β-oxidation and evoked concomitant mobilization of muscle lipid via receptor-mediated activation of muscle lipolysis. αCGRP exerted potent in vivo effects on lipid metabolism in muscle, liver, and the blood via receptor-mediated pathways. Studies with receptor antagonists were consistent with tonic regulation of lipid metabolism by an endogenous CGRP agonist. These data reveal that αCGRP is a newly recognized regulator of lipid availability and utilization in key tissues and that it may elevate the availability of intramyocellular free fatty acids to meet muscle energy requirements generated by contraction by evoking their release from endogenous triglyceride.

scholarly journals Targeting Oxidative Stress with Antioxidant Duotherapy After Experimental Traumatic Brain Injury

2021 ◽  
Vol 22 (19) ◽  
pp. 10555
Author(s):  
Jenni Kyyriäinen ◽  
Natallie Kajevu ◽  
Ivette Bañuelos ◽  
Leonardo Lara ◽  
Anssi Lipponen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Positive Control ◽  
Cortical Lesion ◽  
Favorable Effect ◽  
Neuronal Viability ◽  
Severe Tbi ◽  
Improved Performance ◽  
In Vivo Effects

We assessed the effect of antioxidant therapy using the Food and Drug Administration-approved respiratory drug N-acetylcysteine (NAC) or sulforaphane (SFN) as monotherapies or duotherapy in vitro in neuron-BV2 microglial co-cultures and validated the results in a lateral fluid-percussion model of TBI in rats. As in vitro measures, we assessed neuronal viability by microtubule-associated-protein 2 immunostaining, neuroinflammation by monitoring tumor necrosis factor (TNF) levels, and neurotoxicity by measuring nitrite levels. In vitro, duotherapy with NAC and SFN reduced nitrite levels to 40% (p < 0.001) and neuroinflammation to –29% (p < 0.001) compared with untreated culture. The treatment also improved neuronal viability up to 72% of that in a positive control (p < 0.001). The effect of NAC was negligible, however, compared with SFN. In vivo, antioxidant duotherapy slightly improved performance in the beam walking test. Interestingly, duotherapy treatment decreased the plasma interleukin-6 and TNF levels in sham-operated controls (p < 0.05). After TBI, no treatment effect on HMGB1 or plasma cytokine levels was detected. Also, no treatment effects on the composite neuroscore or cortical lesion area were detected. The robust favorable effect of duotherapy on neuroprotection, neuroinflammation, and oxidative stress in neuron-BV2 microglial co-cultures translated to modest favorable in vivo effects in a severe TBI model.

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.

scholarly journals Camphene Attenuates Skeletal Muscle Atrophy by Regulating Oxidative Stress and Lipid Metabolism in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3731
Author(s):  
Suji Baek ◽  
Jisu Kim ◽  
Byung Seok Moon ◽  
Sun Mi Park ◽  
Da Eun Jung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Muscle Atrophy ◽  
Gas Analysis ◽  
Skeletal Muscle Atrophy ◽  
Ros Scavenging ◽  
In Vivo Models

Sarcopenia- or cachexia-related muscle atrophy is due to imbalanced energy metabolism and oxidative stress-induced muscle dysfunction. Monoterpenes play biological and pharmacological reactive oxygen species (ROS) scavenging roles. Hence, we explored the effects of camphene, a bicyclic monoterpene, on skeletal muscle atrophy in vitro and in vivo. We treated L6 myoblast cells with camphene and then examined the ROS-related oxidative stress using Mito TrackerTM Red FM and anti-8-oxoguanine antibody staining. To investigate lipid metabolism, we performed real-time polymerase chain reactions, holotomographic microscopy, and respiratory gas analysis. Rat muscle atrophy in in vivo models was observed using 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography and immunocytochemistry. Camphene reversed the aberrant cell size and muscle morphology of L6 myoblasts under starvation and in in vivo models. Camphene also attenuated E3 ubiquitin ligase muscle RING-finger protein-1, mitochondrial fission, and 8-oxoguanine nuclear expression in starved myotubes and hydrogen peroxide (H2O2)-treated cells. Moreover, camphene significantly regulated lipid metabolism in H2O2-treated cells and in vivo models. These findings suggest that camphene may potentially affect skeletal muscle atrophy by regulating oxidative stress and lipid metabolism.

scholarly journals Carnosic Acid, a Natural Diterpene, Attenuates Arsenic-Induced Hepatotoxicity via Reducing Oxidative Stress, MAPK Activation, and Apoptotic Cell Death Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-24 ◽  
Author(s):  
Sonjit Das ◽  
Swarnalata Joardar ◽  
Prasenjit Manna ◽  
Tarun K. Dua ◽  
Niloy Bhattacharjee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Apoptotic Cell ◽  
Carnosic Acid ◽  
Protective Mechanism ◽  
Interaction Patterns ◽  
Simultaneous Treatment ◽  
Hepatic Cells ◽  
Cell Death Pathway

The present studies have been executed to explore the protective mechanism of carnosic acid (CA) against NaAsO2-induced hepatic injury. CA exhibited a concentration dependent (1–4 μM) increase in cell viability against NaAsO2 (12 μM) in murine hepatocytes. NaAsO2 treatment significantly enhanced the ROS-mediated oxidative stress in the hepatic cells both in in vitro and in vivo systems. Significant activation of MAPK, NF-κB, p53, and intrinsic and extrinsic apoptotic signaling was observed in NaAsO2-exposed hepatic cells. CA could significantly counteract with redox stress and ROS-mediated signaling and thereby attenuated NaAsO2-mediated hepatotoxicity. NaAsO2 (10 mg/kg) treatment caused significant increment in the As bioaccumulation, cytosolic ATP level, DNA fragmentation, and oxidation in the liver of experimental mice (n=6). The serum biochemical and haematological parameters were significantly altered in the NaAsO2-exposed mice (n=6). Simultaneous treatment with CA (10 and 20 mg/kg) could significantly reinstate the NaAsO2-mediated toxicological effects in the liver. Molecular docking and dynamics predicted the possible interaction patterns and the stability of interactions between CA and signal proteins. ADME prediction anticipated the drug-likeness characteristics of CA. Hence, there would be an option to employ CA as a new therapeutic agent against As-mediated toxic manifestations in future.

Anti-fatigue Effects of Ginseng Antler Yam Tang Modulation of Oxidative Stress Signaling in a Mice Model

2020 ◽  
Author(s):  
Lei Miao ◽  
Rongrong Zhang ◽  
Shuai Shao ◽  
Hongyin Zhang ◽  
Fengqin Xiao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
High Performance ◽  
Antioxidant Activities ◽  
Chemical Components ◽  
Stress Signaling ◽  
Mice Model ◽  
Biochemical Index

Abstract Background: Ginseng Antler Yam Tang (GAYT), believe to invigorate “Qi” (vital energy), nourish “Blood” (body circulation) and engender “liquid” (body fluid), is a traditional Chinese medicine formula derived from the traditional prescription and Chinese traditional medicine partner theory. Methods: In this study, we aimed to evaluate the anti-fatigue effects of GAYT and its mechanisms are related to oxidative stress signaling using GAYT composition, in vitro and in vivo antioxidant, and biochemical index detection. Chemical components analysis of GAYT was performed by high performance liquid chromatography (HPLC) and ultraviolet spectrophotometry (UV). Results: The results show that the GAYT is rich in protein, total flavonoids, total polysaccharide and saponin. The mice model was treatment by GAYT (0.9, 1.8 and 3.6g/kg) for 4 weeks. GAYT treatment enhanced antioxidant activities. GAYT significantly enhances the exercise performance in weight-loaded swimming, rotating rod, and forced running test. Biochemical index levels showed that these effects were closely correlated with inhibiting the depletion of glycogen, blood lactic acid (LD) and adenosine triphosphate (ATP) stores, regulating oxidative stress-related parameters (superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malonaldehyde (MDA)) in serum and liver of mice. Moreover, the results show that the effects of GAYT may be related with its regulation on the activations of AMP-activated protein kinase and protein kinase B in liver of mice.Conclusions: GAYT can induce recovery from fatigue in mice via the activation of the AMPK and AKT/mTOR pathways. Provide a theoretical basis for the study of GAYT's anti-fatigue effect

In vitro and in vivo effects of increased concentrations of free fatty acids on free thyroxin measurements as determined by five assays

1990 ◽  
Vol 36 (4) ◽  
pp. 611-613 ◽  
Author(s):  
R Sapin ◽  
J L Schlienger ◽  
F Grunenberger ◽  
F Gasser ◽  
J Chambron
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
The Other ◽  
In Vitro Experiments ◽  
Fat Emulsion ◽  
Before And After ◽  
High Concentrations ◽  
In Vivo Effects

Abstract To compare in vitro and in vivo effects of increased concentrations of free fatty acids (FFA) on free thyroxin (FT4) values, we measured FT4 in three pooled sera supplemented with oleate and in serum from 18 euthyroid patients before and after an infusion of fat emulsion (Intralipid). We used five FT4 RIA kits: two two-step methods [Gammacoat, Baxter (GC); Ria-gnost, Behring (RG)], two analog RIAs [Amerlex-M, Amersham (AM); Coat-Ria, BioMérieux (CR)], and one kit with labeled antibodies [Amerlex-MAB*, Amersham (AA)]. In vitro, at the maximum oleate addition of 5 mmol/L, FT4 increased when measured by the GC and RG kits, decreased by the AM kit, and showed no significant change by the CR and AA kits. In vivo, post-Intralipid, FFA concentrations rose significantly and the FT4 changes agreed with the results of the in vitro experiments, except for the RG kit, for which FT4 increased in only nine patients. We conclude that in vitro oleate addition is useful to predict the in vivo effect of increased FFA on FT4 values; moreover, in serum from euthyroid subjects with high concentrations of FFA, FT4 analyzed with the CR or AA kits should better agree with normal results for thyrotropin than FT4 values measured with the other kits.

Eugenol attenuates pulmonary damage induced by diesel exhaust particles

2012 ◽  
Vol 112 (5) ◽  
pp. 911-917 ◽  
Author(s):  
Walter A. Zin ◽  
Ana G. L. S. Silva ◽  
Clarissa B. Magalhães ◽  
Giovanna M. C. Carvalho ◽  
Douglas R. Riva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mononuclear Cells ◽  
Pulmonary Inflammation ◽  
Antioxidant Properties ◽  
Diesel Exhaust Particles ◽  
The Other ◽  
Lung Mechanics ◽  
Diesel Particles

Environmentally relevant doses of inhaled diesel particles elicit pulmonary inflammation and impair lung mechanics. Eugenol, a methoxyphenol component of clove oil, presents in vitro and in vivo anti-inflammatory and antioxidant properties. Our aim was to examine a possible protective role of eugenol against lung injuries induced by diesel particles. Male BALB/c mice were divided into four groups. Mice received saline (10 μl in; CTRL group) or 15 μg of diesel particles DEP (15 μg in; DIE and DEUG groups). After 1 h, mice received saline (10 μl; CTRL and DIE groups) or eugenol (164 mg/kg; EUG and DEUG group) by gavage. Twenty-four hours after gavage, pulmonary resistive (ΔP1), viscoelastic (ΔP2) and total (ΔPtot) pressures, static elastance (Est), and viscoelastic component of elastance (ΔE) were measured. We also determined the fraction areas of normal and collapsed alveoli, amounts of polymorpho- (PMN) and mononuclear cells in lung parenchyma, apoptosis, and oxidative stress. Est, ΔP2, ΔPtot, and ΔE were significantly higher in the DIE than in the other groups. DIE also showed significantly more PMN, airspace collapse, and apoptosis than the other groups. However, no beneficial effect on lipid peroxidation was observed in DEUG group. In conclusion, eugenol avoided changes in lung mechanics, pulmonary inflammation, and alveolar collapse elicited by diesel particles. It attenuated the activation signal of caspase-3 by DEP, but apoptosis evaluated by TUNEL was avoided. Finally, it could not avoid oxidative stress as indicated by malondialdehyde.

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