Quantitative synergism

KHAFIF A, SCHANTZ s P, CHOU T c, EDELSTEIN D and SACKS P G (1998) Quantitation of chemopreventive synergism between epigallocatechin gallate and curcumin in normal, premalignant, and malignant oral epithelial cells . Carcinogenesis, 19, 419-24. 

An alluring field of research is the mechanism of action of oxidation inhibitors. This research will undoubtedly yield in the near future a theory for inhibition of undesirable oxidation processes. The relatively stable free radicals observed on such inhibition display extremely interesting properties. Of great interest are the effects of synergism, of inhibitor mixtures, and of mixtures of inhibitors with catalysts. A strictly quantitative and elegant description of all these phenomena may be made within the scope of the chain theory for slow oxidation. 

The necessity of dispersion of nanofillers for enhancement of properties of nanocomposites has been well-documented. Literature describes various techniques used for preparation of the rubber-based nanocomposites [5]. These processes have their inherent pros and cons, but seldom have these issues been quantitatively documented or the processes combined together to synergize and overcome the failings of a technique. 

The determination of a permissible exposure to a toxic substance requires evaluation of qualitative and quantitative factors including the identification and health significance of the adverse effect the sensitive members of and the size of the exposed population, biological absorption, distribution, metabolism, and excretion and the possible additivity, synergism, or antagonism with coexposed substances. 

Synergism has been expressed quantitatively by different ways. If DA, DB and D(A+B) respectively are the distribution ratios of a metal ion, under identical conditions, with extractants A, B and their mixture, containing the same concentration of each extractant used separately, it follows that... 

Thus, there is hardly any extractant combination which is free from mutual association and this factor has to be taken into account in any quantitative study on synergic extraction. 

Khafif, A., Schantz, S.P., Chou, T.C., Edelstein, D. and Sacks, P.C. (1998) Quantitation of chemopreventive synergism between (—)-epiga11ocatechin-3-gaI late and curcumin in normal, premalignant and malignant human oral epithelial cells. Carcinogenesis 1 9, 41 9-424. 

Thus, synergisms and antagonisms are defined in quantitative terms, in relation to a specific additivity expectation. The additive effects of a combination of chemicals that can be calculated by using CA or IA serve as a point of reference for identifying a synergism or antagonism. 

Based on these considerations, the following 2 minimal quality criteria for low-dose mixture experiments suggest themselves for assessments of studies published in the literature 1) The effects of individual mixture components should have been determined under conditions similar to those of the mixture. 2) NOAELs (or NOELs and NOECs when a neutral effect concept is adopted) should have been estimated for each mixture component, and the absence of observable effects demonstrated directly. In addition to these 2 minimal requirements, it would be desirable to calculate quantitative additivity expectations. This would allow evaluations of combination effects in terms of synergism, antagonism, or additivity. 

Gaumont Y, Kisliuk RL, Parsons JC, Greco WR. 1992. Quantitation of folic-acid enhancement of antifolate synergism. Cancer Res 52 2228-2235. 

Greco WR, Park HS, Rustum YM. 1990. An application of a new approach for the quantitation of drug synergism to the combination of cis-diamminedichloroplatinum and 1-b-D-arabinosefuranosylcytosine. Cancer Res 50 5318-5327. 

The basic information which the sanitary engineer requires is a quantitative evaluation of toxicity under any set of environmental conditions. As discussed below, it is difficult to arrive at such an evaluation. The magnitude of the toxicity observed or reported is a function of several factors including concentration, antagonism, synergism, complex formation, and acclimation. Each of these is discussed in turn. 

If this method is used in reporting data, it will no longer be necessary to use non-quantitative terms such as toxicity, antagonism, synergism, stimulation, and etc. Because of the absolute nature of this method of reporting results and its freedom from ambiguity, all future studies of the effect of metabolites on metabolism should utilize this reporting method. 

The synergism of the catalytic action of (tetraphenylpophyrinato)manganese(III) chloride [Mn" (TTP)Cl] and methyltrioctylammonium chloride was demonstrated by their joint appication for the PTC oxidation of benzyl alcohol with NaClO [88], Benzaldehyde is formed within several minutes in almost quantitative yield. The reaction proceeds much more slowly when only one of these catalysts is used. 

Plants appear to have certain quaUtative and quantitative strategies for designing their PUFA/tocopherol mixtures (1) y-tocopherol appears to be the main antioxidant for the depot lipids of oilseeds and nuts, especially those rich in hnolenic acid (2) both a-and p-tocopherols and tocotrienols are important for the protection of PUFA of cereal grains and (3) lipids in the green parts of plants are usually protected by low amounts of a-tocopherol synergized by other phenohc and non-phenolic antioxidants (Kamal-Eldin, 1999). The thermal stabihty of tocopherols increases in the following order a-tocopherol < p-tocopherol < y-tocopherol 5-tocopherol (Yoshida and Tagaki, 1999). 

---