scholarly journals Atomically precise silver clusterzymes protect mice from radiation damages

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jiao Guo ◽  
Haiyu Yang ◽  
Ya Liu ◽  
Wei Liu ◽  
Ruiying Zhao ◽  
...  
Keyword(s):  
Cell Viability ◽  
High Efficiency ◽  
Disease Diagnosis ◽  
The Body ◽  
Water Soluble ◽  
Whole Body ◽  
Dna Damages ◽  
Γ Ray

Abstract Background As we know, radiotherapy plays an irreplaceable role in the clinical management on solid tumors. However, due to the non-specific killing effects of ionizing radiation, normal tissues damages would be almost simultaneous inevitably. Therefore, ideal radioprotective agents with high efficiency and low toxicity are always desirable. In this work, atomically precise Ag14 clusterzymes were developed, and their applications in radioprotection were studied in vitro and in vivo for the first time. Methods The ultra-small glutathione supported Ag14 clusterzymes were synthesized by convenient sodium borohydride (NaBH4) reduction of thiolate-Ag (I) complexes and then they were purified by desalting columns. The enzyme-like activity and antioxidant capacity of Ag14 clusterzymes have been tested by various commercial kits, salicylic acid method and electron spin resonance (ESR). Next, they were incubated with L929 cells to evaluate whether they could increase cell viability after γ-ray irradiation. And then Ag14 clusterzymes were intravenously injected into C57 mice before 7 Gy whole-body γ-ray irradiation to evaluate the radioprotection effects in vivo. At last, the in vivo toxicities of Ag14 clusterzymes were evaluated through biodistribution test, hematological details, serum biochemical indexes and histological test in female Balb/c mice with intravenous injection of Ag14 clusterzymes. Results Our studies suggested atomically precise Ag14 clusterzymes were potential radioprotectants. Ag14 clusterzymes exhibited unique superoxide dismutase (SOD)-like activity, strong anti-oxidative abilities, especially on •OH scavenging. The Ag14 clusterzymes could effectively improve cell viability through eliminating ROS and prevent DNA damages in cells dealt with γ-ray irradiation. In vivo experiments showed that Ag14 clusterzymes could improve the irradiated mice survival rate by protecting hematological systems and repairing tissue oxidative stress damage generated by γ-ray irradiation. In addition, bio-distribution and toxicological experiments demonstrated that the ultrasmall Ag14 clusterzymes could be excreted quickly from the body by renal clearance and negligible toxicological responses were observed in mice up to 30 days. Conclusion In summary, atomically precise, ultrasmall and water soluble Ag14 clusterzymes with SOD-like activity were successfully developed and proved to be effective both in vitro and in vivo for radioprotection. Furthermore, with atomically precise molecular structure, Ag14 clusterzymes, on aspect of the catalytic and optical properties, may be improved by structure optimization on atom-scale level for other applications in disease diagnosis and treatment. Graphical Abstract

Human Skin Binding and Absorption of Contaminants from Ground and Surface Water During Swimming and Bathing

1989 ◽  
Vol 8 (5) ◽  
pp. 853-859 ◽  
Author(s):  
Ronald C. Wester ◽  
Howard I. Maibach
Keyword(s):  
Surface Water ◽  
Stratum Corneum ◽  
Human Skin ◽  
The Body ◽  
Water Soluble ◽  
Exposure Effect ◽  
Human Stratum Corneum ◽  
Water Dilution

Contaminants exist in ground and surface water. Human skin has the capacity to bind and then absorb these contaminants into the body during swimming and bathing. Powdered human stratum corneum will bind both lipid-soluble (alachlor, polychlorinated biphenyls [PCBs], benzene) and water-soluble (nitroaniline) chemicals. In vitro (human skin) and in vivo (Rhesus monkey) studies show that these chemicals readily distribute into skin, and then some of the chemical is absorbed into the body. Linearity in binding and absorption exists for nitroaniline over a 10-fold concentration range. Multiple exposure to benzene is at least cumulative. Binding and absorption can be significant for exposures as short as 30 min, and will increase with time. Absorption with water dilution increased for alachlor, but not for dinoseb. Soap reversed the partitioning of alachlor between human stratum corneum and water. The PCBs could be removed from skin by soap and water (70% efficiency) for up to 3 h and then decontamination potential decreased, due to continuing skin absorption. The model in vitro and in vivo systems used should permit easy estimation of this area of extensive human exposure effect on risk assessment.

Polyphenols in Food: Cancer Prevention and Apoptosis Induction

2018 ◽  
Vol 25 (36) ◽  
pp. 4740-4757 ◽  
Author(s):  
Ashita Sharma ◽  
Mandeep Kaur ◽  
Jatinder Kaur Katnoria ◽  
Avinash Kaur Nagpal
Keyword(s):  
Cancer Prevention ◽  
Defense Mechanism ◽  
Antioxidant Property ◽  
The Body ◽  
Water Soluble ◽  
Stress Factors ◽  
In Vivo Studies ◽  
Hydroxyl Groups

Polyphenols are a group of water-soluble organic compounds, mainly of natural origin. The compounds having about 5-7 aromatic rings and more than 12 phenolic hydroxyl groups are classified as polyphenols. These are the antioxidants which protect the body from oxidative damage. In plants, they are the secondary metabolites produced as a defense mechanism against stress factors. Antioxidant property of polyphenols is suggested to provide protection against many diseases associated with reactive oxygen species (ROS), including cancer. Various studies carried out across the world have suggested that polyphenols can inhibit the tumor generation, induce apoptosis in cancer cells and interfere in progression of tumors. This group of wonder compounds is present in surplus in natural plants and food products. Intake of polyphenols through diet can scavenge ROS and thus can help in cancer prevention. The plant derived products can also be used along with conventional chemotherapy to enhance the chemopreventive effects. The present review focuses on various in vitro and in vivo studies carried out to assess the anti-carcinogenic potential of polyphenols present in our food. Also, the pathways involved in cancer chemopreventive effects of various subclasses (flavonoids, lignans, stilbenes and phenolic acids) of polyphenols are discussed.

High Resolution NMR Spectroscopy on Whole-Body Imagers:Optimized Single-and Multi-Pulse Experiments in Vitro

1995 ◽  
Vol 50 (10) ◽  
pp. 942-948
Author(s):  
Fritz Schick
Keyword(s):  
Aqueous Solutions ◽  
Spin Echo ◽  
Single Pulse ◽  
Spin Systems ◽  
The Body ◽  
Coupling Constants ◽  
Whole Body ◽  
Receiver Coil

Abstract From 100 ml spherical glass bottles filled with aqueous solutions and suspended in a homogeneous magnetic field, NMR spectra with linewidths of about 0.7 Hz were achieved in single-pulse and multi-pulse spectra. A relatively wide receiver coil as the body coil or the standard head coil of the manufacturer were employed to acquire spectra after different non-localized pulse sequences. Examples of single-pulse spectra and double spin-echo spectra of aqueous solutions with lactate, citrate, or glucose are demonstrated and discussed. The fact that all experiments can be performed using well-defined pulse angles acting on the entire sample at the field strenght of the whole-body unit allows to determine the characteristics (e.g. chemical shift differences, coupling constants) of spin systems of biologically important molecules precisely, without need for additional spectrometers. Constant flip angles are advantageous for adequate theoretical analysis of spectra from coupled spin systems. The effects of a defined "misadjustment" of the transmitter on the spectra can be measured directly, whereas localized methods always yield a superposition of signals due to the distribution of flip angles inside the selected volume. In some cases, optimized sequence parameters for localized examinations in vivo can be derived numerically from the analyzed coupling data.

In Vitro Cytotoxicity and In Vivo Tissue Response Study of Foreign Bodies Iron Based Materials

2015 ◽  
Vol 1112 ◽  
pp. 449-452 ◽  
Author(s):  
Deni Noviana ◽  
Sri Estuningsih ◽  
Devi Paramitha ◽  
Mokhammad Fakhrul Ulum ◽  
Hendra Hermawan
Keyword(s):  
Foreign Body ◽  
Cell Viability ◽  
Direct Method ◽  
The Body ◽  
Tissue Response ◽  
Ion Concentration ◽  
Ion Release ◽  
Iron Based

A foreign body is any object originating outside the body. It may migrate from its entry site and cause pain, inflammation and infection. This study aims to examine in vitro cytotoxicity and in vivo tissue response at different implantation sites of two iron-based foreign body (FeFB) specimens: pure Fe wire, Cr-coated Fe wire, and SS316L wire as control. In vitro cytotoxicity was assessed towards rat smooth muscle cells with direct method of methyl thiazolyl tetrazolium (MTT) assay. In vivo tissue response was examined using mice animal model until day 14 after surgical implantation in subcutaneous nape area and intramuscular right femoral muscle. Cell viability, surface morphology and Fe ion release were examined. Implant density and tissue response were examined by using radiographic imaging and histology, respectively. Results showed that both FeFB specimens exhibited similar cell viability with SS316L. Iron ion concentration was higher in both FeFB medium compared to that of SS316L and with oxide layer formation on their surface. Radiographic analysis showed that the density of both FeFB implants end-side was increased. Meanwhile, histological tissue response at intramuscular sites for FeFB specimens showed a prominent inflammatory response compared to SS316L. Detailed analysis on cell and tissue-material interactions of the iron-based foreign body specimens is discussed further in this article.

scholarly journals Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Victor Paromov ◽  
Sudha Kumari ◽  
Marianne Brannon ◽  
Naga S. Kanaparthy ◽  
Hongsong Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Cell Viability ◽  
Sulfur Mustard ◽  
Alkylating Agents ◽  
Water Soluble ◽  
Model Systems ◽  
Mustard Gas

Sulfur mustard or mustard gas (HD) and its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES), or “half-mustard gas,” are alkylating agents that induce DNA damage, oxidative stress, and inflammation. HD/CEES are rapidly absorbed in the skin causing extensive injury. We hypothesize that antioxidant liposomes that deliver both water-soluble and lipid-soluble antioxidants protect skin cells from immediate CEES-induced damage via attenuating oxidative stress. Liposomes containing water-soluble antioxidants and/or lipid-soluble antioxidants were evaluated usingin vitromodel systems. Initially, we found that liposomes containing encapsulated glutathione (GSH-liposomes) increased cell viability and attenuated production of reactive oxygen species (ROS) in HaCaT cells exposed to CEES. Next, GSH-liposomes were tested in a human epidermal model, EpiDerm. In the EpiDerm, GSH-liposomes administered simultaneously or 1 hour after CEES exposure (2.5 mM) increased cell viability, inhibited CEES-induced loss of ATP and attenuated changes in cellular morphology, but did not reduce caspase-3 activity. These findings paralleled the previously describedin vivoprotective effect of antioxidant liposomes in the rat lung and established the effectiveness of GSH-liposomes in a human epidermal model. This study provides a rationale for use of antioxidant liposomes against HD toxicity in the skin considering further verification in animal models exposed to HD.

scholarly journals Combretastatins: An Overview of Structure, Probable Mechanisms of Action and Potential Applications

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2560 ◽  
Author(s):  
Gökçe Şeker Karatoprak ◽  
Esra Küpeli Akkol ◽  
Yasin Genç ◽  
Hilal Bardakcı ◽  
Çiğdem Yücel ◽  
...  
Keyword(s):  
South African ◽  
Water Solubility ◽  
The Body ◽  
Water Soluble ◽  
In Vivo Studies ◽  
Lead Compounds ◽  
Combretastatin A4 ◽  
Potential Applications

Combretastatins are a class of closely related stilbenes (combretastatins A), dihydrostilbenes (combretastatins B), phenanthrenes (combretastatins C) and macrocyclic lactones (combretastatins D) found in the bark of Combretum caffrum (Eckl. & Zeyh.) Kuntze, commonly known as the South African bush willow. Some of the compounds in this series have been shown to be among the most potent antitubulin agents known. Due to their structural simplicity many analogs have also been synthesized. Combretastatin A4 phosphate is the most frequently tested compounds in preclinical and clinical trials. It is a water-soluble prodrug that the body can rapidly metabolize to combretastatin A4, which exhibits anti-tumor properties. In addition, in vitro and in vivo studies on combretastatins have determined that these compounds also have antioxidant, anti-inflammatory and antimicrobial effects. Nano-based formulations of natural or synthetic active agents such as combretastatin A4 phosphate exhibit several clear advantages, including improved low water solubility, prolonged circulation, drug targeting properties, enhanced efficiency, as well as fewer side effects. In this review, a synopsis of the recent literature exploring the combretastatins, their potential effects and nanoformulations as lead compounds in clinical applications is provided.

scholarly journals Gold-Polymer Nanocomposites for Future Therapeutic and Tissue Engineering Applications

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 70
Author(s):  
Panangattukara Prabhakaran Praveen Kumar ◽  
Dong-Kwon Lim
Keyword(s):  
Tissue Engineering ◽  
Polymer Nanocomposites ◽  
Disease Diagnosis ◽  
The Body ◽  
Hybrid Nanocomposites ◽  
Surface Charges ◽  
Engineering Applications ◽  
Therapeutic Applications

Gold nanoparticles (AuNPs) have been extensively investigated for their use in various biomedical applications. Owing to their biocompatibility, simple surface modifications, and electrical and unique optical properties, AuNPs are considered promising nanomaterials for use in in vitro disease diagnosis, in vivo imaging, drug delivery, and tissue engineering applications. The functionality of AuNPs may be further expanded by producing hybrid nanocomposites with polymers that provide additional functions, responsiveness, and improved biocompatibility. Polymers may deliver large quantities of drugs or genes in therapeutic applications. A polymer alters the surface charges of AuNPs to improve or modulate cellular uptake efficiency and their biodistribution in the body. Furthermore, designing the functionality of nanocomposites to respond to an endo- or exogenous stimulus, such as pH, enzymes, or light, may facilitate the development of novel therapeutic applications. In this review, we focus on the recent progress in the use of AuNPs and Au-polymer nanocomposites in therapeutic applications such as drug or gene delivery, photothermal therapy, and tissue engineering.

In vivo n.m.r. imaging in medicine: the Aberdeen approach, both physical and biological

1980 ◽  
Vol 289 (1037) ◽  
pp. 519-533 ◽  
Keyword(s):  
Pulse Sequence ◽  
The Body ◽  
Spin Lattice Relaxation ◽  
Surrounding Tissue ◽  
Whole Body ◽  
Spin Concentration ◽  
Stage Of Development ◽  
Wide Range

A novel magnetic field and radio frequency (1.7 MHz) pulse sequence is described for a whole body n.m.r. imaging machine under construction. Selective excitation is used to obtain signals from successive lines of proton spins (water) across the body to build up an image of a transverse section. The images display spin concentration and spin-lattice relaxation time, T 1 , separately. For a 50 % change in T 1 to be discerned in the human trunk, a spatial resolution of 2 cm 3 is expected for a 2 min scan and 0.5 cm 3 for a 30 min scan. Very preliminary images at the present incomplete stage of development show the geometrical accuracy and T 1 discrimination: an in vivo image demonstrates some of the difficulties to be overcome. In vitro measurements of normal rabbit tissue samples have been made at 24 MHz to map the T 1 distributions that can be expected from normal subjects. The transposition of this information from rabbit to man, and from 24 MHz to 2.5 MHz have been checked and the comparison shown to be meaningful. Of pathological samples, human breast tumour and human liver metastases offer a good contrast to their surrounding tissue, and an experimental investigation has shown that tissue immediately surrounding a tumour also has an elevated T 1 value. A wide range of abnormalities that are associated with abnormal fluid formation in the body may be amenable to imaging by the n.m.r. technique. Potential hazards are believed to be small in the present generation of equipment.

scholarly journals Evaluation of Aminopolycarboxylate Chelators for Whole-Body Clearance of Free 225Ac: A Feasibility Study to Reduce Unexpected Radiation Exposure during Targeted Alpha Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1706
Author(s):  
Mitsuyoshi Yoshimoto ◽  
Yukie Yoshii ◽  
Hiroki Matsumoto ◽  
Mitsuhiro Shinada ◽  
Masashi Takahashi ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
Feasibility Study ◽  
The Body ◽  
Whole Body ◽  
Targeted Alpha Therapy ◽  
Carboxylic Groups ◽  
Alpha Therapy ◽  
Body Clearance

Actinium-225 (225Ac) is a promising radionuclide used in targeted alpha therapy (TAT). Although 225Ac labeling of bifunctional chelating ligands is effective, previous in vivo studies reported that free 225Ac can be released from the drugs and that such free 225Ac is predominantly accumulated in the liver and could cause unexpected toxicity. To accelerate the clinical development of 225Ac TAT with a variety of drugs, preparing methods to deal with any unexpected toxicity would be valuable. The aim of this study was to evaluate the feasibility of various chelators for reducing and excreting free 225Ac and compare their chemical structures. Nine candidate chelators (D-penicillamine, dimercaprol, Ca-DTPA, Ca-EDTA, CyDTA, GEDTA TTHA, Ca-TTHA, and DO3A) were evaluated in vitro and in vivo. The biodistribution and dosimetry of free 225Ac were examined in mice before an in vivo chelating study. The liver exhibited pronounced 225Ac uptake, with an estimated human absorbed dose of 4.76 SvRBE5/MBq. Aminopolycarboxylate chelators with five and six carboxylic groups, Ca-DTPA and Ca-TTHA, significantly reduced 225Ac retention in the liver (22% and 30%, respectively). Significant 225Ac reductions were observed in the heart and remainder of the body with both Ca-DTPA and Ca-TTHA, and in the lung, kidney, and spleen with Ca-TTHA. In vitro interaction analysis supported the in vivo reduction ability of Ca-DTPA and Ca-TTHA. In conclusion, aminopolycarboxylate chelators with five and six carboxylic groups, Ca-DTPA and Ca-TTHA, were effective for whole-body clearance of free 225Ac. This feasibility study provides useful information for reducing undesirable radiation exposure from free 225Ac.

scholarly journals Aminopolycarboxylate Chelators Are Effective for Whole-body Clearance of Free 225ac: A Method to Reduce Unexpected Radiation Exposure During Targeted Alpha Therapy

2021 ◽  
Author(s):  
Mitsuyoshi Yoshimoto ◽  
Yukie Yoshii ◽  
Hiroki Matsumoto ◽  
Mitsuhiro Shinada ◽  
Masashi Takahashi ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
The Body ◽  
Whole Body ◽  
Targeted Alpha Therapy ◽  
Carboxylic Groups ◽  
In Vitro Interaction ◽  
Alpha Therapy ◽  
Body Clearance

Abstract Purpose: Actinium-225 (225Ac) is a promising radionuclide used in targeted alpha therapy (TAT). Although 225Ac labelling of bifunctional chelating ligands is effective, previous in vivo studies have reported that free 225Ac can be released from the drugs. Notably, such free 225Ac predominantly accumulates in the liver and can cause unexpected toxicity. To accelerate the clinical development of 225Ac TAT, methods for addressing unexpected toxicity are therefore needed. In this study, we evaluated various chelators in vitro and in vivo with regard to reducing and excreting free 225Ac and compared their chemical structures. Methods: Nine candidate chelators (D-penicillamine, dimercaprol, Ca-DTPA, Ca-EDTA, CyDTA, GEDTA TTHA, Ca-TTHA, and DO3A) were tested. In vitro interaction of 225Ac and chelators was investigated. Biodistribution and dosimetry of free 225Ac were examined in mice prior to the in vivo chelating study. For in vivo chelation, nine candidate chelators were administered 1 h after free 225Ac injection, and biodistribution was compared 4 h after 225Ac injection in mice. Two favourable chelators were then investigated intensively for biodistribution 24 h after the 225Ac injection.Results: The liver exhibited pronounced 225Ac uptake corresponding to an estimated human absorbed dose of 4.76 SvRBE5/MBq. Aminopolycarboxylate chelators with five and six carboxylic groups, Ca-DTPA and Ca-TTHA, significantly reduced 225Ac retention in the liver (22% and 30%, respectively). Significant 225Ac reductions were observed in the heart and the remainder of the body with both Ca-DTPA and Ca-TTHA, and in the lung, kidney, and spleen for Ca-TTHA. In vitro interaction analysis supported the in vivo reduction ability of Ca-DTPA and Ca-TTHA.Conclusions. Aminopolycarboxylate chelators with five and six carboxylic groups, Ca-DTPA and Ca-TTHA, were effective for whole-body clearance of free 225Ac, with a significant reduction in the liver. This method could reduce undesirable radiation exposure from free 225Ac during 225Ac TAT.

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