Membrane-associated toxicity

The primary routes of entry for animal exposure to chromium compounds are inhalation, ingestion, and, for hexavalent compounds, skin penetration. This last route is more important in industrial exposures. Most hexavalent chromium compounds are readily absorbed, are more soluble than trivalent chromium in the pH range 5 to 7, and react with cell membranes. Although hexavalent compounds are more toxic than those of Cr(III), an overexposure to compounds of either oxidation state may lead to inflammation and irritation of the eyes, skin, and the mucous membranes associated with the respiratory and gastrointestinal tracts. Skin ulcers and perforations of nasal septa have been observed in some industrial workers after prolonged exposure to certain hexavalent chromium compounds (108—110), ie, to chromic acid mist or sodium and potassium dichromate. 

Fluoroacetate undergoes a "lethal synthesis"(18) to 2-fluorocitrate which may reversibly inhibit aconitase and which irreversibly binds to a membrane-associated citrate transport protein(19,20). Insecticidal and other biocidal uses of fluoroacetate (or its metabolic precursors) received considerable attention twenty-five years ago( ) but most uses have been abandoned due to high nonspecific vertebrate toxicity of these compounds. Vfe have reported the use of o)-fluoro fatty acids and their derivatives as delayed-action toxicants for targeted... 

C41 and C43 BL21 BL21 mutants that over-produce membranes enables expression of membrane-associated and toxic proteins... 

Both the plasma membrane and internal membranes associated with organelles may be damaged by toxic compounds. Chemicals such as detergents, strong acids and alkalies, and snake venoms, which contain hydrolytic enzymes, can also directly damage the plasma membrane. 

Mercuric chloride, other mercury-containing antibacterials and silver will inhibit enzymes in the membrane, and for that matter in the cytoplasm, which contain thiol, -SH, groups. A similar action is shown by 2-bromo-2-nitropropan-l,3-diol (bronopol) and /so-thiazolones. Under appropriate conditions the toxic action on cell thiol groups may be reversed by addition of an extrinsic thiol compound, e.g. cysteine or thioglycollic acid (see also Chapter 20). Particularly susceptible enzymes are the dehydrogenases involved in membrane-associated redox processes. 

Most of the IL-1 activity in plasma is from IL-lp, IL-la existing mainly in an intracellular or membrane-associated IL-1 shares many of its functions with TNF, but important differences between IL-1 and TNF exist. For example, IL-1 is in general not toxic, and TNF is a potent cytotoxic effector (see the Biological Actions of TNF section). One of their shared functions is the induction of expression of the vascular cell adhesion molecule (VCAM) by endothelial cells. Studies have indicated that TNF may be more important than IL-1 in induction of VCAM expression at least in the nasal mucosa. ... 

Surfactant Effects on Microbial Membranes and Proteins. Two major factors in the consideration of surfactant toxicity or inhibition of microbial processes are the disruption of cellular membranes b) interaction with lipid structural components and reaction of the surfactant with the enzymes and other proteins essential to the proper functioning of the bacterial cell (61). The basic structural unit of virtually all biological membranes is the phospholipid bilayer (62, 63). Phospholipids are amphiphilic and resemble the simpler nonbiological molecules of commercially available surfactants (i.e., they contain a strongly hydrophilic head group, whereas two hydrocarbon chains constitute their hydrophobic moieties). Phospholipid molecules form micellar double layers. Biological membranes also contain membrane-associated proteins that may be involved in transport mechanisms across cell membranes. 

Some bile salts are quite toxic in the liver, leading to cholestasis and morphologic changes in bile canalicular membranes associated with this toxicity. Some of these toxic bile salts, such as lithocholate and 3 hydroxy-5a-cholanic acid are not detoxified by sulfation, but the sulfate conjugates retain their toxic effects almost completely. Although strictly speaking this is no toxlficatlon by sulfation, yet sulfation does not alleviate toxicity of these compounds (42-45). 

Both the plasma membrane and internal membranes associated with organelles may be damaged by toxic compounds. As already discussed, this may be due to lipid peroxidation which alters and destroys membrane lipids. As many enzymes and transport processes are membrane bound this will affect the function of the organelle as well as the structure. Sulphydryl groups in membranes may be targets for mercuric ions in kidney tubular cells and for methyl mercury in the CNS for example. The result is changes in membrane permeability and transport and subsequent cell death. Structural damage can be... 

Rodriguez Montelongo L, De La Cruz Rodriguez LC, Farias RN and Massa EM (1993) Membrane-associated redox cycling of copper mediates hydroperoxide toxicity in Escherichia coli. Bio-chim Biophys Acta 1144 77-84. 

D. desulfuricans also showed a membrane-associated or soluble nitrate reductase catalyzing the respiratory reduction of nitrate to nitrite [ 134-136]. A cytochrome c-dependent nitrate reductase was also isolated from Geobacter metallireducens [137], Obviously, nitrate uptake and nitrite extrusion into the bulk phase is dispensable for periplasmic nitrate reductases. In addition, a periplasmic location of nitrate reductases will prevent the interaction of potentially toxic compounds such as nitrite or NO with cytoplasmic proteins. 

R. meliloti, like most other bacteria, has many reductases. Some of these are membrane associated and damage to the membrane could affect the reductase. One of these reductases could be responsible for reduction of the dye. It has been found that the MTT is transported into the cell before it is reduced. The reduced dye is inside the cells. Cells with the dye can be concentrated by centrifugation, the dye appears in flie cell pellet. None of the dye is in the supernatant. Toxic chemicals could interfere with the transport of dye into the cell prior to reduetion. 

The high affinity observed for the membrane-associated ascorbate redox cycle in the physiological concentration range (Schweinzer and Goldenberg, 1992) could explain the protection of the cell surface from toxic oxidants and also would be important in keeping extracellular ascorbate in the reduced state, which is the most abundant form in healthy men (Lunec and Blake, 1985). 

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