Choosing the Right Antioxidant Supplement for Protecting Liver from Toxicity of Engineered Nanoparticles : A Comprehensive In Vitro Screening

2016 ◽  
Vol 835 ◽  
pp. 57-62 ◽  
Author(s):  
Hasan Türkez ◽  
Erdal Sönmez ◽  
Elanur Aydin ◽  
Ahmet Hacımuftuoglu ◽  
Elif Öztetik
Keyword(s):  
Rapid Development ◽  
Rat Hepatocytes ◽  
Engineered Nanoparticles ◽  
Artificial Organ ◽  
Zno Nps ◽  
Oxidative Damages ◽  
Antioxidant Supplement ◽  
The Right

With the rapid development of nanotechnology, more and more nanomaterials are being fabricated and manipulated to perform the particular function, such as adhesive, biosensors, cosmetics, drug delivery system and artificial organ and tissue. On the other hand, nanotoxicity has become the topic of concern in nanotechnology because of the serious toxicity potentials of engineered nanomaterials on the living organisms. Many in vivo and in vitro studies clearly indicated that nanoparticles (NPs) are closely associated with toxicity by increasing intracellular reactive oxygen species (ROS) levels. And antioxidant supplementation is considered as useful against nanotoxicity related oxidative damages. At this point, in this investigation we assessed the protective abilities of selected 22 antioxidant or antioxidant featured agents against engineered nanoparticle exposure (ZnO NPs) model. We performed all experiments in cultured primary rat hepatocytes since the liver is a target site for NPs toxicity. Cell viability was detected by [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT) assay and lactate dehydrogenase (LDH) release, while total antioxidant capacity (TAC) and total oxidative stress (TOS) levels were determined to evaluate the oxidative alterations. Our results showed that each agent provided hepatoprotection in different degree. Propolis, boric acid and ascorbic acid were found to be the most effective ones while astaxanthine, L-glutamine and taurine were found to be less effective against nanoparticle induced oxidative injuries. The results presented here can be considered as the first information and rationale strategy on determining hepatoprotective potentials of common antioxidants against NP exposure for choosing the right antioxidant supplement for protecting liver.

Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan
Keyword(s):  
Soft Tissue ◽  
Room Temperature ◽  
Normal Subjects ◽  
Left Testis ◽  
Wide Range ◽  
Activity Ratios ◽  
The Right ◽  
Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

Enhanced Increases in Cytosolic Ca2+ in ADP-Stimulated Platelets from Patients with Delta-Storage Pool Deficiency – A Possible Indicator of Interactions between Granule-Bound ADP and the Membrane ADP Receptor

1997 ◽  
Vol 77 (02) ◽  
pp. 376-382 ◽  
Author(s):  
Bruce Lages ◽  
Harvey J Weiss
Keyword(s):  
Platelet Rich Plasma ◽  
Limited Range ◽  
Dense Granule ◽  
Receptor Desensitization ◽  
Fura 2 ◽  
Storage Pool ◽  
Low Levels ◽  
The Right

SummaryThe possible involvement of secreted platelet substances in agonist- induced [Ca2+]i increases was investigated by comparing these increases in aspirin-treated, fura-2-loaded normal platelets and platelets from patients with storage pool deficiencies (SPD). In the presence and absence of extracellular calcium, the [Ca2+]i response induced by 10 µM ADP, but not those induced by 0.1 unit/ml thrombin, 3.3 µM U46619, or 20 µM serotonin, was significantly greater in SPD platelets than in normal platelets, and was increased to the greatest extent in SPD patients with Hermansky-Pudlak syndrome (HPS), in whom the dense granule deficiencies are the most severe. Pre-incubation of SPD-HPS and normal platelets with 0.005-5 µM ADP produced a dose-dependent inhibition of the [Ca2+]i response induced by 10 µ M ADP, but did not alter the [Ca2+]i increases induced by thrombin or U46619. Within a limited range of ADP concentrations, the dose-inhibition curve of the [Ca2+]i response to 10 µM ADP was significantly shifted to the right in SPD-HPS platelets, indicating that pre-incubation with greater amounts of ADP were required to achieve the same extent of inhibition as in normal platelets. These results are consistent with a hypothesis that the smaller ADP-induced [Ca2+]i increases seen in normal platelets may result from prior interactions of dense granule ADP, released via leakage or low levels of activation, with membrane ADP receptors, causing receptor desensitization. Addition of apyrase to platelet-rich plasma prior to fura-2 loading increased the ADP-induced [Ca2+]i response in both normal and SPD-HPS platelets, suggesting that some release of ADP derived from both dense granule and non-granular sources occurs during in vitro fura-2 loading and platelet washing procedures. However, this [Ca2+]i response was also greater in SPD-HPS platelets when blood was collected with minimal manipulation directly into anticoagulant containing apyrase, raising the possibility that release of dense granule ADP resulting in receptor desensitization may also occur in vivo. Thus, in addition to enhancing platelet activation, dense granule ADP could also act to limit the ADP-mediated reactivity of platelets exposed in vivo to low levels of stimulation.

Toxicity and efficacy evaluation of multiple targeted polymalic acid conjugates for triple-negative breast cancer treatment

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Triple Negative ◽  
Growth Factor Receptor ◽  
Engineered Nanoparticles ◽  
Efficacy Evaluation ◽  
Dual Action ◽  
Epidermal Growth ◽  
Laminin 411 ◽  
Immunologic Analysis

Engineered nanoparticles are widely used for delivery of drugs but frequently lack proof of safetyfor cancer patient's treatment. All-in-one covalent nanodrugs of the third generation have beensynthesized based on a poly(β-L-malic acid) (PMLA) platform, targeting human triple-negativebreast cancer (TNBC). They significantly inhibited tumor growth in nude mice by blockingsynthesis of epidermal growth factor receptor, and α4 and β1 chains of laminin-411, the tumorvascular wall protein and angiogenesis marker. PMLA and nanodrug biocompatibility and toxicityat low and high dosages were evaluated in vitro and in vivo. The dual-action nanodrug and singleactionprecursor nanoconjugates were assessed under in vitro conditions and in vivo with multipletreatment regimens (6 and 12 treatments). The monitoring of TNBC treatment in vivo withdifferent drugs included blood hematologic and immunologic analysis after multiple intravenousadministrations. The present study demonstrates that the dual-action nanoconju-gate is highlyeffective in preclinical TNBC treatment without side effects, supported by hematologic andimmunologic assays data. PMLA-based nanodrugs of the Polycefin™ family passed multipletoxicity and efficacy tests in vitro and in vivo on preclinical level and may prove to be optimizedand efficacious for the treatment of cancer patients in the future.

scholarly journals Functional Characterization of the mazEF Toxin-Antitoxin System in the Pathogenic Bacterium Agrobacterium tumefaciens

2021 ◽  
Vol 9 (5) ◽  
pp. 1107
Author(s):  
Wonho Choi ◽  
Yoshihiro Yamaguchi ◽  
Ji-Young Park ◽  
Sang-Hyun Park ◽  
Hyeok-Won Lee ◽  
...  
Keyword(s):  
Agrobacterium Tumefaciens ◽  
Physiological Function ◽  
Functional Characterization ◽  
Site Directed Mutagenesis ◽  
In Vitro Assays ◽  
Cell Growth Inhibition ◽  
The Right

Agrobacterium tumefaciens is a pathogen of various plants which transfers its own DNA (T-DNA) to the host plants. It is used for producing genetically modified plants with this ability. To control T-DNA transfer to the right place, toxin-antitoxin (TA) systems of A. tumefaciens were used to control the target site of transfer without any unintentional targeting. Here, we describe a toxin-antitoxin system, Atu0939 (mazE-at) and Atu0940 (mazF-at), in the chromosome of Agrobacterium tumefaciens. The toxin in the TA system has 33.3% identity and 45.5% similarity with MazF in Escherichia coli. The expression of MazF-at caused cell growth inhibition, while cells with MazF-at co-expressed with MazE-at grew normally. In vivo and in vitro assays revealed that MazF-at inhibited protein synthesis by decreasing the cellular mRNA stability. Moreover, the catalytic residue of MazF-at was determined to be the 24th glutamic acid using site-directed mutagenesis. From the results, we concluded that MazF-at is a type II toxin-antitoxin system and a ribosome-independent endoribonuclease. Here, we characterized a TA system in A. tumefaciens whose understanding might help to find its physiological function and to develop further applications.

scholarly journals Characterization of the SARS-CoV-2 coronavirus X4-like accessory protein

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Olanrewaju Ayodeji Durojaye ◽  
Nkwachukwu Oziamara Okoro ◽  
Arome Solomon Odiba
Keyword(s):  
Rapid Development ◽  
Protein A ◽  
The Novel ◽  
Quality Model ◽  
A Value ◽  
Model Protein ◽  
Novel Coronavirus ◽  
Global Threat

Abstract Background The novel coronavirus SARS-CoV-2 is currently a global threat to health and economies. Therapeutics and vaccines are in rapid development; however, none of these therapeutics are considered as absolute cure, and the potential to mutate makes it necessary to find therapeutics that target a highly conserved regions of the viral structure. Results In this study, we characterized an essential but poorly understood coronavirus accessory X4 protein, a core and stable component of the SARS-CoV family. Sequence analysis shows a conserved ~ 90% identity between the SARS-CoV-2 and previously characterized X4 protein in the database. QMEAN Z score of the model protein shows a value of around 0.5, within the acceptable range 0–1. A MolProbity score of 2.96 was obtained for the model protein and indicates a good quality model. The model has Ramachandran values of φ = − 57o and ψ = − 47o for α-helices and values of φ = − 130o and ψ = + 140o for twisted sheets. Conclusions The protein data obtained from this study provides robust information for further in vitro and in vivo experiment, targeted at devising therapeutics against the virus. Phylogenetic analysis further supports previous evidence that the SARS-CoV-2 is positioned with the SL-CoVZC45, BtRs-BetaCoV/YN2018B and the RS4231 Bat SARS-like corona viruses.

scholarly journals Advanced Functional Materials Based on Nanocellulose for Pharmaceutical/Medical Applications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1125
Author(s):  
Raluca Nicu ◽  
Florin Ciolacu ◽  
Diana E. Ciolacu
Keyword(s):  
Rapid Development ◽  
Cellulose Nanofibrils ◽  
Functional Materials ◽  
Medical Applications ◽  
Bacterial Nanocellulose ◽  
Green Materials ◽  
Wide Range ◽  
In Vivo Cytotoxicity

Nanocelluloses (NCs), with their remarkable characteristics, have proven to be one of the most promising “green” materials of our times and have received special attention from researchers in nanomaterials. A diversity of new functional materials with a wide range of biomedical applications has been designed based on the most desirable properties of NCs, such as biocompatibility, biodegradability, and their special physicochemical properties. In this context and under the pressure of rapid development of this field, it is imperative to synthesize the successes and the new requirements in a comprehensive review. The first part of this work provides a brief review of the characteristics of the NCs (cellulose nanocrystals—CNC, cellulose nanofibrils—CNF, and bacterial nanocellulose—BNC), as well as of the main functional materials based on NCs (hydrogels, nanogels, and nanocomposites). The second part presents an extensive review of research over the past five years on promising pharmaceutical and medical applications of nanocellulose-based materials, which have been discussed in three important areas: drug-delivery systems, materials for wound-healing applications, as well as tissue engineering. Finally, an in-depth assessment of the in vitro and in vivo cytotoxicity of NCs-based materials, as well as the challenges related to their biodegradability, is performed.

scholarly journals Pharmacologically mechanistic basis for the traditional uses of Rumex acetosa in gut motility disorders and emesis

2015 ◽  
Vol 10 (3) ◽  
pp. 548 ◽  
Author(s):  
Musaddique Hussain ◽  
Shahid Masood Raza ◽  
Khalid Hussain Janbaz
Keyword(s):  
Rumex Acetosa ◽  
Response Curves ◽  
Motility Disorders ◽  
Traditional Uses ◽  
Antiemetic Activity ◽  
Rabbit Jejunum ◽  
Mechanistic Basis ◽  
The Right

<p class="Abstract"><em>In vitro</em> and<em> in vivo</em> studies were undertaken to evaluate the pharmacologically mechanistic background to validate the traditional uses of <em>Rumex acetosa</em> in the treatment of emesis and gastrointestinal motility disorders such as constipation and diarrhea. In rabbit jejunum preparation, methanolic extract of <em>R. acetosa</em> (0.01-1.0 mg/mL) caused a transient spasmogenic effect, followed by the spasmolytic effect (3-10 mg/mL). In presence of atropine, spasmogenic effect was blocked while spasmolytic effect was emerged, suggesting that spasmogenic effect was mediated through activation of muscarinic receptors. Extract inhibited the K<sup>+ </sup>(80 mM)-induced contraction, suggesting Ca<sup>2+</sup>-cha-nnel blockade, which was further confirmed when pretreatment of tissue with extract shifted the Ca<sup>2+ </sup>concentration-response curves to the right, similarly as verapamil.<em> R. acetosa</em> also exhibited the significant antiemetic activity (p&lt;0.05) against different emetogenic stimuli, when compared with chlorpromazine. This study confirms the presence of gut modulator (spasmogenic and spasmolytic) and antiemetic activates, validating its traditional uses.</p><p> </p>

scholarly journals Oxygen and Carbon Dioxide Transport Characteristics of the Blood of the Nile Monitor Lizard (Varanus Niloticus)

1987 ◽  
Vol 130 (1) ◽  
pp. 27-38
Author(s):  
JAMES W. HICKS ◽  
ATSUSHI ISHIMATSU ◽  
NORBERT HEISLER
Keyword(s):  
Carbon Dioxide ◽  
Haemoglobin Concentration ◽  
Oxygen Affinity ◽  
Total Blood ◽  
Carbon Dioxide Transport ◽  
Monitor Lizard ◽  
The Right ◽  
Dissociation Curves

Oxygen and carbon dioxide dissociation curves were constructed for the blood of the Nile monitor lizard, Varanus niloticus, acclimated for 12h at 25 and 35°C. The oxygen affinity of Varanus blood was low when Pco2 w a s in the range of in vivo values (25°C: P50 = 34.3 at PCOCO2 = 21 mmHg; 35°C: P50 = 46.2 mmHg at PCOCO2 = 35 mmHg; 1 mmHg = 133.3 Pa), and the oxygen dissociation curves were highly sigmoidal (Hill's n = 2.97 at 25°C and 3.40 at 35°C). The position of the O2 curves was relatively insensitive to temperature change with an apparent enthalpy of oxygenation (ΔH) of −9.2kJ mol−1. The carbon dioxide dissociation curves were shifted to the right with increasing temperature by decreasing total CCOCO2 at fixed PCOCO2, whereas the state of oxygenation had little effect on total blood CO2 content. The in vitro buffer value of true plasma (Δ[HCO3−]pl/-ΔpHpl) rose from 12.0 mequiv pH−1−1 at 25°C to 17.5 mequiv pH−11−1 at 35°C, reflecting a reversible increase of about 30% in haemoglobin concentration and haematocrit levels during resting conditions in vivo.

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