Additives, mode of action

By definition, the uncoupling effect of certain flavonoids should be independent of their inhibitory effects on mitochondrial respiration or FoFi-ATPase, suggesting an additional mode of action of flavonoids against mitochondrial function. A collapse of the transmembrane potential is likely under conditions in which the permeability barrier created by the mitochondrial inner membrane is compromised (as occurs in the presence of ionophores). Calcium, phosphate, oxidative stress, adenine nucleotide depletion, and membrane depolarization can induce such a nonspecific increase in the permeability of the inner membrane, in an event called the mitochondrial permeability transition (MPT) [30,34]. The MPT can be selectively inhibited by cyclosporin A and is believed to involve the assembly of a multiprotein complex to form a nonspecific pore that spans the inner and outer mitochondrial membranes. The latter assembly is referred to as the permeability transition pore complex (PTPC) (Fig. 1). Its exact composition is unknown, but appears to comprise cyclophilin D, ANT, the voltage-dependent anion channel (porin), and a benzodiazepinebinding site [10,30,34]. 

This chapter is divided in two parts additives for motor fuels and additives for lubricants. Concerning additives for gasoline, one will find here in Chapter 9 some useful complements to Chapter 5, especially regarding the synthesis of additives and their modes of action. 

One can distinguish three important additive classes according to their modes of action ... 

In polymers such as polystyrene that do not readily undergo charring, phosphoms-based flame retardants tend to be less effective, and such polymers are often flame retarded by antimony—halogen combinations (see Styrene). However, even in such noncharring polymers, phosphoms additives exhibit some activity that suggests at least one other mode of action. Phosphoms compounds may produce a barrier layer of polyphosphoric acid on the burning polymer (4,5). Phosphoms-based flame retardants are more effective in styrenic polymers blended with a char-forming polymer such as polyphenylene oxide or polycarbonate. 

Phosphoms-containing additives can act in some cases by catalyzing thermal breakdown of the polymer melt, reducing viscosity and favoring the flow or drip of molten polymer from the combustion zone (25). On the other hand, red phosphoms [7723-14-0] has been shown to retard the nonoxidative pyrolysis of polyethylene (a radical scission). For that reason, the scavenging of radicals in the condensed phase has been proposed as one of several modes of action of red phosphoms (26). 

It should be noted that dmgs may operate by more than one mechanism, and may possess a specific mode of action against one species of plasmodium but lack efficacy against others. In addition, antimalarial dmgs may be classified according to their stmctural types. 

The majority of analgesics can be classified as either central or peripheral on the basis of their mode of action. Structural characteristics usually follow the same divisions the former show some relation to the opioids while the latter can be recognized as NSAlD s. The triamino pyridine 17 is an analgesic which does not seem to belong stmcturally to either class. Reaction of substituted pyridine 13 (obtainable from 12 by nitration ) with benzylamine 14 leads to the product from replacement of the methoxyl group (15). The reaction probably proceeds by the addition elimination sequence characteristic of heterocyclic nucleophilic displacements. Reduction of the nitro group with Raney nickel gives triamine 16. Acylation of the product with ethyl chlorofor-mate produces flupirtine (17) [4]. 

In the stabilization of PVC, the principal mode of action of the various stabilizer systems has been explained in terms of the Frye and Horst mechanism, i.e., substitution of labile chlorines by more stable groups. Evidence for other actions, such as HCl neutralization, addition to polyene sequences, and bimetallic complex formation have also been given. Despite the wide acceptance of the Frye and Horst mechanism, researchers have frequently contended that this could not be the dominant mechanism in the stabilization of PVC. 

There is an extremely wide range of potentially useful chemical treatments available, and for any boiler system, proper selection, utilization, and control are vital considerations that may largely determine the ultimate success of the overall program. These chemicals usually are organized by type of compound, function, mode of action, or similar classification, but, because many chemicals are multifunctional in character, may be used in either a primary or supplementary (adjunct or conjunctional treatment) role, and additionally may be branded (especially many modem polymers) or otherwise disguised, such classifications may be quite arbitrary. 

The mechanisms of degradation and the mode of action of the various PVC stabilisers have both been widely studied. Often at least one aspect of their operation is some sort of reaction with the first trace of hydrogen chloride evolved. This removes what would otherwise act as the catalyst for further dehydrochlorination, and hence significantly retards the degradation process. In addition, many stabilisers are themselves capable of reacting across any double bonds formed, thereby reversing the process that causes discoloration and embrittlement. 

The final possible mode of action for an antioxidant is as a peroxide decomposer. In the sequences that lead to photodegradation of a polymer the ready fragmentation of the hydroperoxide groups to free radicals is the important step. If this step is interfered with because the peroxide has undergone an alternative decomposition this major source of initiation is removed. The additives which act by decomposing hydroperoxide groups include compounds containing either divalent sulfur or trivalent phosphorus. The mechanism involves... 

Four examples will now be given of such mechanistic biomarker assays that can give integrative measures of toxic action by pollutants, all of which have been described earlier in the text. Where the members of a group of pollutants share a common mode of action and their effects are additive, TEQs can, in principle, be estimated from their concentrations and then summated to estimate the toxicity of the mixture. In these examples, toxicity is thought to be simply related to the proportion of the total number sites of action occupied by the pollutants and the toxic effect additive where two or more compounds of the same type are attached to the binding site. 

Particular attention is given to the development of new mechanistic biomarker assays and bioassays that can be used as indices of the toxicity of mixtures. These biomarker assays are typically based on toxic mechanisms such as brain acetylcholinesterase inhibition, vitamin K antagonism, thyroxin antagonism, Ah-receptor-mediated toxicity, and interaction with the estrogenic receptor. They can give integrative measures of the toxicity of mixtures of compounds where the components of the mixture share the same mode of action. They can also give evidence of potentiation as well as additive toxicity. 

Some metabolites of curcumin (particularly tetrahydrocurcumin) may also participate in producing the observed effects of curcumin in different models because these metabolites display greater stabilities than the parent curcumin molecule at physiological pH. Recent data show similar modes of action of curcumin metabolites regarding antioxidant enzyme induction and inhibition of multidrug-resistant proteins. " Additional data indicate that curcumin may even act against other types of diseases such as atherosclerosis " " and Alzheimer s disease. " - " ... 

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