Alleviation of genotoxic effects of cyclophosphamide using encapsulation into liposomes in the absence or presence of vitamin C.

Tohamy AA, Abdel Azeem AA, Shafaa MW, Mahmoud WS

Gen Physiol Biophys. 2012 Mar;31(1):85-91. doi: 10.4149/gpb_2012_009.

Cyclophosphamide (CP) is a widely used anticancer and immunosuppressant that induces oxidative stress. To ameliorate the side effects resulted from CP treatment, liposomes were tested as an efficient drug delivery system with or without vitamin C as an antioxidant. CP resulted in clastogenic and cytotoxic effects that significantly increased for the total chromosomal aberrations as well as the numerical ones in the CP group (150.8 and 6, respectively) than the control group (6.6 and 0.0) as mean values at p < 0.05. Micronucleus assay showed a significant increased micronucleated polychromatic erythrocytes percentage (MNPCEs% = 11.7%) and a significant decrease of polychromatic to normochromatic erythrocytes ratio (0.551) when compared to the group treated with liposomised CP and vitamin C (3.44%; 0.795, respectively) at p < 0.05. Also, the total glutathione S-transferase activity as a body antioxidant enzyme was decreased from 52.2 in the control to 16.09 nmol/min/mg protein in CP group at p < 0.05, while the highly significant amelioration results were observed in the liposomised vitamin C and CP group (40.88 nmol/min/mg protein). Our findings support the potential use of CP in a liposomal formulation doped with vitamin C to diminish the potential side effects of the agent.

Thermally induced conformational changes in horseradish peroxidase

David G. Pina1 et al.
Eur. J. Biochem. 268, 120-126 (2001), FEBS 2001

REACTIVE OXYGEN SPECIES: Metabolism, Oxidative Stress, and Signal Transduction

Klaus Apel and Heribert Hirt

Annu. Rev. Plant Biol. 2004. 55:373–99

Several reactive oxygen species (ROS) are continuously produced in plants as byproducts of aerobic metabolism. Depending on the nature of the ROS species, some are highly toxic and rapidly detoxified by various cellular enzymatic and nonenzymatic mechanisms. Whereas plants are surfeited with mechanisms to combat increased ROS levels during abiotic stress conditions, in other circumstances plants appear to purposefully generate ROS as signaling molecules to control various processes including pathogen defense, programmed cell death, and stomatal behavior. This review describes the mechanisms of ROS generation and removal in plants during development and under biotic and abiotic stress conditions. New insights into the complexity and roles that ROS play in plants have come from genetic analyses of ROS detoxifying and signaling mutants. Considering recent ROS-induced genomewide expression analyses, the possible functions and mechanisms for ROS sensing and signaling in plants are compared with those in animals and yeast.

Free radicals and antioxidants in normal physiological functions and human disease

Marian Valko, Dieter Leibfritz, Jan Moncol, Mark T.D. Cronin, Milan Mazur, Joshua Telser

The International Journal of Biochemistry & Cell Biology 39 (2007) 44–84

Reactive oxygen species (ROS) and reactive nitrogen species (RNS, e.g. nitric oxide, NO•) are well recognised for playing a dual role as both deleterious and beneficial species. ROS and RNS are normally generated by tightly regulated enzymes, such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. Overproduction of ROS (arising either from mitochondrial electron transport chain or excessive stimulation of NAD(P)H) results in oxidative stress, a deleterious process that can be an important mediator of damage to cell structures, including lipids and membranes, proteins, andDNA. In contrast, beneficial effects ofROS/RNS (e.g. superoxide radical and nitric oxide) occur at low/moderate concentrations and involve physiological roles in cellular responses to noxia, as for example in defence against infectious agents, in the function of a number of cellular signalling pathways, and the induction of a mitogenic response. Ironically, various ROS-mediated actions in fact protect cells against ROS-induced oxidative stress and re-establish or maintain “redox balance” termed also “redox homeostasis”. The “two-faced” character of ROS is clearly substantiated. For example, a growing body of evidence shows that ROS within cells act as secondary messengers in intracellular signalling cascades which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. This review will describe the: (i) chemistry and biochemistry of ROS/RNS and sources of free radical generation; (ii) damage to DNA, to proteins, and to lipids by free radicals; (iii) role of antioxidants (e.g. glutathione) in the maintenance of cellular “redox homeostasis”; (iv) overview of ROS-induced signaling pathways; (v) role of ROS in redox regulation of normal physiological functions, as well as (vi) role of ROS in pathophysiological implications of altered redox regulation (human diseases and ageing). Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease), rheumatoid arthritis, and ageing. Topics of current debate are also reviewed such as the question whether excessive formation of free radicals is a primary cause or a downstream consequence of tissue injury.

Lipopolysaccharide Identification with Functionalized Polydiacetylene Liposome Sensors

Marianne Rangin and Amit Basu
J. AM. CHEM. SOC. 2004, 126, 5038-50

Polydiacetylene Liposome Microarray Toward Influenza A Virus Detection: Effect of Target Size on Turn-On Signaling

1. Sungbaek Seo¹, 
2. Jiseok Lee¹, 
3. Eun-Jin Choi², 
4. Eun-Ju Kim², 
5. Jae-Young Song²,
6. Jinsang Kim^3,*

Volume 34, Issue 9, pages 743–748, May 14, 2013

Target size effect on the sensory signaling intensity of polydiacetylene (PDA) liposome microarrays was systematically investigated. Influenza A virus M1 peptide and M1 antibody were selected as a probe–target pair. While red fluorescence from the PDA liposome microarrays was observed when the larger M1 antibody was used as a target, when the same M1 antibody was used as a probe to detect the smaller M1 peptide sensory signal did not appear. The results reveal that the intensity of the PDA sensory signal is mainly related to the steric repulsion between probe–target complexes not the strength of the probe–target binding force. Based on this finding, we devised a PDA sensory system that directly detects influenza A whole virus as a larger target, and confirmed the target size effect on the signaling efficiency of PDA.

A Light-Actuated Nanovalve Derived from a Channel Protein

Armagan Kocer, Martin Walko, Wim Meijberg, Ben L. Feringa

29 JULY 2005 VOL 309 SCIENCE, pp.755

Toward the realization of nanoscale device control, we report a molecular valve embedded in a membrane that can be opened by illumination with longwavelength ultraviolet (366 nanometers) light and then resealed by visible irradiation. The valve consists of a channel protein, the mechanosensitive channel of large conductance (MscL) from Escherichia coli, modified by attachment of synthetic compounds that undergo light-induced charge separation to reversibly open and close a 3-nanometer pore. The system is compatible with a classical encapsulation system, the liposome, and external photochemical control over transport through the channel is achieved.

Shape and Size of a Nonionic Surfactant Micelle. Triton X-100 in Aqueous Solution

H. Hasko Paradies

J. Phys. Chem. 1980, 84, 599-607

Phase Separation of Polymerized Mixed Liposomes: Analysis of Release Behavior of Entrapped Molecules with Skeletonization

Shinji Takeoka, Hiromi Sakai, Hiroyuki Ohno,+ and Eishun Tsuchida'

Macromolecules 1991,24, 1279-1283

The mixed liposomes, composed of a polymerizable lipid, 1,2-bis(2,4-octadecadienoyl)-snglycero-3-phosphorylcholine(D ODPC), and nonpolymerizable membrane constituents, DPPC, cholesterol, and sodium didodecyl phosphate, were prepared by an extrusion method. After polymerization, onpolymerizable constituents were removed to obtain the polymerized framework of the liposome (the skeletonized liposome). The release of small molecules from the skeletonized liposomes through resulting holes was analyzed. A 5(6)-carboxyfluorescein (CF) and saccharides with various molecular weights were applied as release molecules. The molecular weight of dextran, whose retention ratio in the skeletonized liposomes is 5096, relates to the apparent size of the holes, i.e., the apparent domain size of the phase separation of a polymerized mixed liposome. The size of the holes increases with an increase in the mole fraction of nonpolymerizable lipids. This also depends on the polymerization temperature and the structure of nonpolymerizable lipids.

Thermodynamics of micelle formation and surface chemical behavior of p-tert-Octylphenoxyethylene Ether (TritonX-100) in Aqueous Medium

J. Surface Sci. Technol., Vol 17, no.1-2, pp.1-15, 2001

LIPOSOMES OF CONTROLLABLE SIZE IN THE RANGE OF 40 TO 180 nm BY DEFINED DIALYSIS OF LIPID/DETERGENT MIXED MICELLES

OTMAR ZUMBUEHL and HANS GEORG WEDER

Biochimica et Biophysica Acta, 640 (1981) 252-262

Liposomes, in the size range of 40--180 nm, are formed when lipid and additives are solubllized with detergent, yielding defined mixed micelles, and the detergent is subsequently removed by controlled dialysis. Their most important properties are that they are indeed unilamellar with usefully large encapsulated volumes and are homogeneous in size. Liposomes have been formed from both natural and synthetic phospholipids with cholesterol and charged molecules added. This relatively simple technique may be particularly useful for encapsulating drugs, enzymes and other macromolecules and in studies of reconstitution of membrane proteins.