Membrane permeability alterations

This process is an early morphological change in cells often seen in isolated cells in vitro but also known to occur in vivo. The blebs, which appear before membrane permeability alters, are initially reversible. However, if the toxic insult is sufficiently severe and the cellular changes become irreversible, the blebs may rupture. If this occurs, vital cellular components may be lost and cell death follows. The occurrence of blebs may be due to damage to the cytoskeleton, which is attached to the plasma membrane as described above. The cause may be an increase in cytosolic Ca2+, interaction with cytoskeletal proteins, or modification of thiol groups (see below). 

Similar to hydrophilic flavonoids, hydrophobic flavonoids can affect membrane permeability. Alterations in this biophysical property of liposome bilayers lead to the release of bulky molecules entrapped into the inner aqueous space. As mentioned in the previous section, a strong correlation was found between flavonoid retention to a hydrophobic matrix and their capacity to induce membrane leakage [Ollila et al., 2002]. Interestingly, hydrophilic flavonoids, such as (—)-epicatechin and related procyanidins (dimer to hex-amer) prevented Fe2 + -mediated liposome permeabilization, although in this case the beneficial effect could be related to both their antioxidant and metal chelating capacities and their membrane stabilizing properties [Verstraeten et al., 2004],... 

TBT and TFT are membrane-active molecules, and their mechanism of action appears to be strongly dependent on organotin(IV) lipophilicity. They function as ionophores and produce hemolysis, release Ca(II) from sarcoplasmic reticulum, alter phosphatodylseiine-induced histamine release, alter mitochondrial membrane permeability and perturb membrane enzymes. Organotin(IV) compounds have been shown to affect cell signaling they activate protein kinase and increase free arachidonic acid through the activation of phospholipase... 

Figure 15-8. Mechanisms of control of an enzyme-catalyzed reaction. Circled numbers indicate possible sites of action of hormones. .Alteration of membrane permeability conversion of an inactive to an active enzyme, usually in-...

Based on this model of active mineral absorption, one can hypothesize several ways that allelochemicals could Inhibit mineral absorption (1) alter the PD, (2) Inhibit ATPases, (3) decrease cellular ATP content, and (4) alter membrane permeability to Ions. 

Alteration of Membrane Permeability. The ability of allelochemicals to alter membrane permeability and thus inhibit mineral absorption has been investigated in detail with only phenolic acids. Salicylic acid induced the efflux of PO5 (28) and 1C" (42) from barley roots, but -hydroxybenzoic acid did not cause the efflux of K+... 

A third possibility is that mineral ions leak out of tissue in the presence of phenolic acids, not because membrane permeability is altered, but rather because the driving force that maintains high ion concentrations in cells (i.e. PD) is dissipated by the chemicals. Without an electrical potential, ions would distribute solely according to their chemical concentrations. Thus, most ions would leak out of cells to reach chemical equilibrium with the external environment. 

The reported (14) mechanisms of action of allelochemlcals Include effects on root ultrastructure and subsequent Inhibition of Ion absorption and water uptake, effects on hormone-induced growth, alteration of membrane permeability, changes In lipid and organic acid metabolism, inhibition of protein synthesis and alteration of enzyme activity, and effects on stomatal opening and on photosynthesis. Reduced leaf water potential Is one result of treatment with ferulic and p-coumaric acids (15). Colton and Einhellig (16) found that aqueous extracts of velvetleaf (Abutllon theophrastl Medic.) Increased diffusive resistance In soybean fGlycine max. (L.) Merr.] leaves, probably as a result of stomatal closure. In addition, there was evidence of water stress and reduced quantities of chlorophyll In Inhibited plants. 

Precellular solute ionization dictates membrane permeability dependence on mucosal pH. Therefore, lumenal or cellular events that affect mucosal microclimate pH may alter the membrane transport of ionizable solutes. The mucosal microclimate pH is defined by a region in the neighborhood of the mucosal membrane in which pH is lower than in the lumenal fluid. This is the result of proton secretion by the enterocytes, for which outward diffusion is slowed by intestinal mucus. (In fact, mucosal secretion of any ion coupled with mucus-restricted diffusion will provide an ionic microclimate.) Important differences in solute transport between experimental systems may be due to differences in intestinal ions and mucus secretion. It might be anticipated that microclimate pH effects would be less pronounced in epithelial cell culture (devoid of goblet cells) transport studies than in whole intestinal tissue. 

In some human studies where clinical chemistry measurements but no renal biopsies were performed, the only parameter of renal function shown to be affected was an increase in the levels of NAG in the urine. NAG is a lysosomal enzyme present in renal tubular cells that has been shown to be a sensitive indicator of early subclinical renal tubular disease. The mechanism by which lead affects the release of NAG from renal tubular cells is not known, but it is suggested that lead could attach to kidney cell membranes and alter membrane permeability (Chia et al. 1994). 

Once apoptosis is triggered, a stereotyped sequence of premitochondrial events occurs that executes the cell death process. In many cases proteins and/or lipid mediators that induce changes in mitochondrial membrane permeability and calcium regulation are produced or activated. For example, the pro-apoptotic Bcl-2 family members Bax, Bad and Bid may associate with the mitochondrial membrane and modify its permeability. Membrane-derived lipid mediators such as ceramide and 4-hydroxynonenal can also induce mitochondrial membrane alterations that are critical for the execution of apoptosis. 

No data were found on the effects of silver compounds on avian or mammalian wildlife. All controlled studies with silver were with domestic poultry, livestock, or small laboratory mammals. Signs of chronic silver ion intoxication in tested birds and mammals included cardiac enlargement, vascular hypertension, hepatic necrosis, anemia, lowered immunological activity, altered membrane permeability, kidney pathology, enzyme inhibition, growth retardation, and a shortened life span (Smith and Carson 1977 Freeman 1979 Fowler and Nordberg 1986 USPHS 1990). 

Finally, the chemistry of the organism must be taken into account. Interrelationships among metals can rarely be explained on a purely chemical basis (i.e. inhibition of the uptake of the metal of interest and uptake of the competing metal). Even metals exhibiting the expected chemical antagonisms, may also initiate a cellular feedback, alter the overall biological metabolism or modify membrane permeability or the cells capacity to deal with the metal of interest. 

A clue as to why the cationic N-terminal region and the hydrophobic C-terminal portion of SP are required for full histamine-releasing activity comes from studies of the electrical conductivity of black lipid membranes in the presence of peptides. Using SP, these authors [176] concluded that SP probably binds by its N-terminal region to negatively charged sites on membrane lipids, while the C-terminal portion of the molecule penetrates the hydrophobic core of the lipid bilayer, which could induce an increase in membrane permeability or a slight alteration in membrane conformation. 

Pharmacology Vancomycin is a tricyclic glycopeptide antibiotic that inhibits cell-wall biosynthesis. It also alters bacterial-cell-membrane permeability and RNA synthesis. Pharmacokinetics ... 

Uses Severe, systemic fungal Infxns oral cutaneous candidiasis Action Binds ergosterol in the fungal membrane to alter permeability Dose Adults Peds. Test dose 1 mg IV adults or 0.1 mg/kg to 1 mg IV in children then 0.25-1.5 mg/kg/24 h IV over 2-6 h (range 25-50 mg/d or qod). Total dose varies w/ indication PO 1 mL qid Caution [B, ] Disp Inj SE -1- K /Mg from renal wasting anaphylaxis reported, HA, fever, chills, n hrotox, -1- BP, anemia, rigors Notes -1- In renal impair pre-Tx w/ APAP antihistamines (Benadryl) X SE Interactions T Nephrotoxic effects W/ antineoplastics, cyclosporine, furosemide, vancomycin, aminoglycosides, T hypokalemia W/ corticost oids, skeletal muscle relaxants EMS May cause electrolyte imbalances, monitor ECG OD May effect CV and resp Fxn symptomatic and supportive... 

Amphotericin B Cholesteryl (Amphotec) [Antifungal/Polyene Mocrollde] Uses AspCTgillosis if intolCTant/refractory to conventional amphotericin B, systemic candidiasis Action Binds ceU membrane sterols, alters permeability Dose Adults Peds. Test dose 1.6—8.3 mg, over 15-20 min, then 3-4 mg/kg/d 1 mg/kg/h inf w/ renal insuff Caution [B, ] Disp Inj SE Anaphylaxis fever, chills, HA, nephrotox, -1- BP, anemia Notes Do not use in-line filter Interactions See Amphotericin B EMS See AmphotCTicin B OD May cause cardiac arrest s ptomatic and supportive... 

In addition to studies with whole cells and tissues, it has also been shown that the permeability of isolated organelles can be altered by ozone exposure. For example, Lee (11) showed that ozone altered the permeability of tobacco mitochondria, and Coulson and Heath (12) reported membrane permeability changes of isolated chloroplasts after ozone exposure. 

It is rather difficult to rationalize a decreased membrane permeability to water (Lp) because of oxidant exposure. We suspect, therefore, that the apparent decreased water permeability results in fact from a decreased reflection coefficient leading to solute loss and hence an apparent lower water transport rate. In any case, these data clearly demonstrate the occurrence of oxidant-induced alterations in membrane properties. 

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