Effects on Cell Permeability

8 BIOACTIVITIES OF SINAPINE, SINAPIC ACID 2.8.1 Effects on Cell Permeability 

There is only a single reference on the effects of rapeseed/canola phenolics on cell permeability. Satu et al. (2005) indicated that the crude rapeseed oil phenolic extract had no significant effect on the permeability of the model drugs. However, rapeseed meal phenolics enhanced the permeability of verapamil and ketoprofen indicating that they may have an impact on drugs and other components being actively transported across the cell membrane. 

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The addition of heparin to the isolated rat diaphragm previously loaded with rubidium 86 results in change of the inflow of rubidium . Heparin has a permeabilizing action which appears to be due to mobilization of bound potassium and this can be related to a reduction of calcium in the perfusion solution. Karasek and Mourek.i conclude that heparin depresses oxidative processes through an effect on cell permeability it is possible that it adsorbs certain substances such as potassium chloride or acetylcholine. In extracorporeal dialysis , heparin causes an apparent decrease of 60 per cent in plasma calcium concentration. Heparin also forms a chelate-like compound with calcium ions " . This process is usually unimportant as heparin absorbs a maximum of only 5 per cent of its weight of calcium, but with intradermal, intramuscular or subcutaneous administration, heparin may deplete the capillary walls of calcium and cause them to become fragile. Heparin alsc decreases wound strength 6-14 days after operation in some experiments and may delay the union of fractures in bone repair . Heparin, but not chondroitin sulphate or hyaluronic acid, in tissue culture increases the amount of bone resorption in the presence of suboptimal concentrations of parathyroid extracts, and thus may be a cofactor in bone metabolism. ... 

Histidine decarboxylase from E. coli has a pH optimum near 4.0, while a similar enzyme assayed in Clostridium welchii has a pH optimum near 2.5. Extracts of acetone- or dioxane-treated C. welchii, however, have maximal rates of histidine decarboxylation at pH 4.5. The reason for the difference in pH optima of intact cells and extracts is conventionally attributed to pH effects on cell permeability, but other factors may be responsible. It is noteworthy in this connection that the Km of histidine is the same for both types of preparation. For years no cofactor could be found for this enzyme, but recently it was found that both pyridoxal phosphate and Fe+++ or Al are required. ... 

Although it is widely believed that the effects of ozone on cell permeability are the basis of ozone toxicity,the chemical basis of the effects on membranes is still arguable. It is still not clear whether the first effect of ozone is on the protein or lipid components of the cell. 

Critical for predictivity in a recent comprehensive study was the number and choice of parameters measured [4]. Early, sublethal effects on cell proliferation, cell morphology and mitochondria occurred consistently and ubiquitously with toxicity and when used collectively were most diagnostic. It is noteworthy that the toxicity of many drugs is attributable to various mitochondrial targets, including oxidative phosphorylation, fatty acid oxidation, Krebs cycling, membrane transport, permeability transition pore, proliferation and oxidative stress (Table 14.4). 

The effect of soyasaponins on tumor cells may be mediated by mechanisms other than membrane permeability, because of their weak hemolytic activity. Saponins actively interact with cell membrane components, resulting in changes in intracellular morphology and cell membrane permeability. However, the differences between types of saponins and their effects on cell membrane are evident. 

Recently another electrically assisted drug delivery technology, electroporation, was proposed as an alternative or adjuvant to iontophoresis. Electroporation comprises the use of electric pulses to induce transient changes in the cell membrane architecture that turn it into more permeable barrier. Beside the permeabilization effect on cell membrane, it was postulated that this technique induces electrophoretic effect on charged macromolecules and drives them to move across the destabilized membrane [205]. 

Note Use PI to analyze the effects of CPP-ON conjugates on cell permeability. 

The cell membrane serves as a protective barrier in renal cells. It is the initial site which p-lactams encounter in their journey to the cellular environment from the blood or tubular fluid, p-lactams may disrupt the functional organization of the membrane through peroxidation of membrane lipids, which, in turn, leads to the inability of membrane to serve as an osmotic barrier and causes the cytosol contents to leak. As a result of the cephalosporins disruptive effect on cell membrane, increased leakage of the cytosolic enzyme lactate dehydrogenase (LDH) occurs. The increased LDH concentration was from the cytosol of the renal cortex [49,71] or from isolated proximal and distal tubular cells [39] or in the urine of experimental animals [39]. The results of these studies indicate that plasma membrane became permeable to large molecules such as LDH. After cephalosporin treatment, cephaloridine caused the greatest decrease of LDH concentration in cytosol [49]. Whereas, cephaloridine induced a greater release of LDH from proximal tubular cells than cepha-lothin and cephalexin, distal cells were not affected by any of these cephalosporins [38,39]. 

ACE inhibitors and ARBs slow the progression of diabetic kidney disease. A trial that was reported in 2000 confirmed that even nonmicroalbuminuric type 2 diabetic patients should be managed with ACE inhibitors or ARBs to prevent cardiovascular events.In addition to lowering systemic blood pressure, such patients also have lowered glomerular capillary blood pressure and protein filtration,ACE inhibitors and ARBs also reduce All-medi-ated effects on glomerular permeability and cell proliferation and fibrosis and should be incorporated into the treatment schedules of all patients with type 2 diabetes and those with type 1 diabetes and microalbuminuria, ACE inhibitors may exacerbate hyperkalemia in patients with advanced CKD and/or hyporeninemic hypoaldosteronism. In older patients with renal artery stenosis, they may cause a rapid decline in kidney function. Pooled data from large clinical trials indicated above show that only 1.5% of patients treated with ACE inhibitors or ARBs were withdrawn from trials because of hyperkalemia, and no deaths were reported as a consequence of hyperkalemia. ... 

Similar approaches to enhance solubility have been studied in the PAMPA system. For instance, Kansy et al. (2001) explored the use of glycocholic acid to solubilize compounds. As PAMPA is a completely artificial system, it is expected that, compared to cell-based models, higher concentrations of cosolvents can be used. Sugano and coworkers reported that DMSO, ethanol and PEG 400 could be used up to 30% without causing disruptions of the lipid layer (Sugano et al., 2001). An effect of these cosolvents on the physicochemical properties of the test compounds (e.g. impact on pKa) may however lead to an unpredictable effect on drug permeability (Sugano et al., 2001). Currently, DMSO is commonly used as a cosolvent in the PAMPA system at a concentration of 1 to 2%. 

Very few investigations have dealt with the uptake of stable Sr " " and its possible effects on plant growth. Isermann (1981) reported, in an extended review of strontium uptake by plants and its effects on plant growth, that strontium is not primarily toxic to higher plants in the presence of calcium. Furthermore, it has some beneficial effect on cell integrity and permeability, on the net uptake of essential plant nutrients, and on respiration. Weinberg (1977) reported that for amylase, when strontium was substituted for calcium, the enzyme had full activity but varied in some physical properties. 

Movements of small hydrophilic solutes across human and probably other biological membranes can be affected by certain sulfhydryl-reactive reagents such as PCMBS and by phloretin. In the case of human red-cell membrane, a system which has been thoroughly studied in this respect, either one of these two compounds inhibits drastically the movements of these molecules. As is evident in Table 5, the inhibitory effect on the permeability decreases as the value increases. Whereas the... 

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