Salicylic acid, absorption

Salicylic Acid Absorption. The apical 5 cm of the primary and two seminal roots from each of three plants were out into 1-cm segments to form an experimental unit (ca. 0.08 g). Incubation solution cc ijjtalned 0.5 mM KCl, 0.25 mM CaSOjj, 0.5 mM salicylic acid, 10 nCl/mL [ C]-sallcyllc acid, with 25 mM Tris and 25 mM Mes buffers mixed to obtain pH 6.5. Because the salicylic acid was dissolved in absolute ethanol, the final concentration of ethanol in the incubation solution was 1 (v/v). Root segments were transferred to test tubes containing 10 mL continuously aerated incubation solution. After the predetermined absorption time, segments were collected from the incubation solution by rapid filtration on Whatman No. 2 filter paper. 

Figure 9.6 The dependence of salicylic acid absorption on the net water flux (positive sign flow directed from the lumen and towards the blood) in the rat jejunal loop perfused with hypo-, iso- and hypertonic solutions at pH 6.2 and 2.2. The lines, mean values with 95% confidence limits (shaded areas), were calculated by means of the parameters determined by a kinetic model with the following constants concentration of salicylic acid in the perfusion solution 32.3 /

Many pharmaceutical compounds contain chromophores that make them suitable for analysis by UV/Vis absorption. Products that have been analyzed in this fashion include antibiotics, hormones, vitamins, and analgesics. One example of the use of UV absorption is in determining the purity of aspirin tablets, for which the active ingredient is acetylsalicylic acid. Salicylic acid, which is produced by the hydrolysis of acetylsalicylic acid, is an undesirable impurity in aspirin tablets, and should not be present at more than 0.01% w/w. Samples can be screened for unacceptable levels of salicylic acid by monitoring the absorbance at a wavelength of... 

Discussion. Salicylic acid and iron(III) ions form a deep-coloured complex with a maximum absorption at about 525 nm this complex is used as the basis for the photometric titration of iron(III) ion with standard EDTA solution. At a pH of ca 2.4 the EDTA-iron complex is much more stable (higher stability constant) than the iron-salicylic acid complex. In the titration of an iron-salicylic acid solution with EDTA the iron-salicylic acid colour will therefore gradually disappear as the end point is approached. The spectrophotometric end point at 525 nm is very sharp. 

A new interpretation of salicylic acid transport across the lipid bilayer implications of pH-dependent but not carrier-mediated absorption from the gastrointestinal tract. /. Pharmacol. 

Another limitation to the studies in Table 1 is the small number of plant species tested. Primarily monocotyledonous plants have been studied, although McClure et al. (26) found ferulic acid inhibitory in soybean. The restriction of studies to monocots is probably because the mechanism of mineral absorption has been more fully elucidated with monocots. Harper and Balke (32) reported some minor differences in the inhibition of K+ absorption by salicylic acid among oats (Avena sativa L.), wheat (Triticum aestlvum L.), barley, and maize roots. 

The short time periods (10 min to 4 hr) over which absorption was measured (Table 1) helps support the hypothesis that certain allelochemicals inhibit mineral absorption directly. Under acidic conditions (pH 4.0) salicylic acid inhibited K+ absorption within 1 min (32). The degree of inhibition remained constant over time when salicylic acid inhibited 1C " absorption (32) and when vanillic acid inhibited P0 absorption (28). Thus, at least phenolic acids appear to inhibit absorption rapidly and consistently. 

Two studies have used single cells to study the effect of phenolic acids on mineral absorption. In sterile cell cultures of Paul s Scarlet rose, 100 pM ferulic acid inhibited Rb+ absorption in about 10 min when the cells were 4-5 days old (37). Uptake from 0.2 mM RbCl was inhibited about 25% and absorption from 5.0 mM RbCl was inhibited 45%. Absorption by 10-day-old cells was affected little. Salicylic acid at 10 pM inhibited PO - absorption by Scenedesmus, a unicellular green alga (38). These studies show that allelochemicals inhibit mineral absorption in cellular systems as well as tissue systems (Table I). 

Salicylic acid depolarized PD In epidermal cells of oat roots also. At pH 4.5, 500 pM salicylic acid caused a transient hyperpolarization followed by a dramatic depolarization to about -45 mV (Figure 2). Removal of salicylic acid produced a transient, partial repolarization. At pH 6.5, salicylic acid did not affect PD. These results with different pH s are consistent with the Influence of salicylic acid on K+ absorption in oat roots (32). 

Benzoic acid derivatives also altered the electrical potential across the cell membrane in neurons of the marine mollusk Navanax lnermls (46). Salicylic acid (1-30 mM) caused a depolarization very rapidly (1-2 min) and decreased the ionic resistance across the membrane. As pH was decreased, more salicylic acid was required to reverse the effect of pH on the membrane potential (47). This result is contradictory to the influence of pH on the amount of salicylic acid required to affect mineral absorption in roots (32). The ability of a series of salicylic and benzoic acid derivatives to increase PD correlated with their octanol/water partition coefficients and pKa values (48). The authors proposed that the organic acid anions bound directly to membranes to produce the observed results. 

Effects of Allelochemlcals on ATPases. Several flavonoid compounds inhibit ATPase activity that is associated with mineral absorption. Phloretin and quercetin (100 pM) inhibited the plasma membrane ATPase Isolated from oat roots (33). The naphthoquinone juglone was inhibitory also. However, neither ferulic acid nor salicylic acid inhibited the ATPase. Additional research has shown that even at 10 mM salicylic acid inhibits ATPase activity only 10-15% (49). This lack of activity by salicylic acid was substantiated with the plasma membrane ATPase Isolated from Neurospora crassa (50) however, the flavonols fisetln, morin, myricetin, quercetin, and rutin were inhibitory to the Neurospora ATPase. Flavonoids inhibited the transport ATPases of several animal systems also (51-53). Thus, it appears that flavonoids but not phenolic acids might affect mineral transport by inhibiting ATPase enzymes. 

Effects of Allelochemlcals on ATP Supply. Allelochemlcals might decrease the ATP content of tissue by either increasing ATP utilization or decreasing ATP production. Some allelochemlcals that inhibit mineral absorption decrease ATP content of plant tissues. Salicylic acid decreased the ATP content of oat roots in a pH dependent manner (Figure 3). This result suggested that mitochondrial production of ATP was decreased in the tissue. On the other hand, Tillberg (38) found that salicylic acid and cinnamic acid increased the ATP content of Scenedesmus. Various flavonoids inhibited ATP production by mitochondria Isolated from cucumber (Cucumls satlvus L.) hypocotyls (54). Flavones such as kaempferol were more inhibitory than the corresponding flavanones. Substituted cinnamic acids such as caffeic acid were not inhibitory. 

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+... 

It remains to be determined if one or both of these hypotheses are correct for plant roots. One feature of the inhibition of absorption by salicylic acid (and probably other phenolic acids) that may be relevant to this point is whether the neutral acid or the anion is responsible for the inhibition. In oat roots, the amount of neutral acid present when salicylic acid caused 50% Inhibition of K+ absorption was constant regardless of pH (Figure 6). However, the concentration of anion present changed several orders of magnitude. This result suggests the neutral acid is the species... 

Takagi, M. Taki, Y. Sakane, T. Nadai, T. Sezaki, H. Oku, N. Yamashita, S., A new interpretation of salicylic acid transport across the lipid bilayer Implication of pH-dependence but not carrier-mediated absorption from the gi tract, J. Pharmacol. Exp. Therapeut. 285, 1175-1180 (1998). 

Figure 7 (Left panel) Relative absorption rate for a weak acid (pKa = 3) as a function of mucosal pH for increasing barrier (membrane) permeability (Pb) with fixed unstirred aqueous layer permeability (Pul). X = pHinflectionpoint in Eq. (4). (Right panel) Partition coefficient-dependent absorption rates for salicylic acid and the weak base ephedrine. (From Ref. 19.)...

At present, the relevance of these results to photode-gradationl 0f condensates 1 is a matter of speculation. Of particular interest is identification of the photoproduct quencher(s) (PP, Scheme I). Possible candidates are salicylic acid derivatives, which exhibit the requisite absorptivity at about 300 nm, and which may be formed by oxidation of ortho-photo-Fries products (Scheme III), as illustrated in eq. 1. 

Kurosaki Y, Hisaichi S, Nakayama T, Kimura T (1989a) Enhancing effect of l-dodecylazacycloheptan-2-one (Azone) on the absorption of salicylic acid from keratinized oral mucosa and the duration of enhancement in vivo. Int J Pharm 51 47-54... 

Utoguchi N, Watanabe Y, Takase Y, Suzuki T, Matsumoto M (1999) Carrier-mediated absorption of salicylic acid from hamster cheek pouch mucosa. J Pharm Sci 88 142-146... 

Topical products for removal of corns and calluses often contain salicylic acid at a concentration of between 11% and 50% as a keratolytic agent in combination with lactic acid, the latter intended to aid absorption. 

Ester hydrolysis does not invariably lead to inactive metabolites, as exemplified by acetylsalicylic acid. The cleavage product, salicylic acid, retains pharmacological activity. In certain cases, drugs are administered in the form of esters in order to facilitate absorption (enalapril enalaprilate testosterone undecanoate testosterone) or to reduce irritation of the gastrointestinal Lullmann, Color Atlas of Pharmacology... 

The complexes [Ru(bpy)2L]+ (HL = acetylacetone, trifluoroacetylacetone, hexafluoroacetylace-tone, tropolone or dibenzoylmethane) have been prepared and characterized they act as catalysts for the oxidation of alcohols, 3,5-di-tert-butylcatechol and alkanes in the presence of appropriate co-oxidants." Perchlorate salts of [Os(bpy)2L] in which HL = salicylaldehyde, 2-hydroxyaceto-phenone or 2-hydroxynaphthaldehyde, are formed from reactions of [Os(bpy)2Br2] with HL. The structure of the salicylaldehyde derivative has been determined. Chemical and electrochemical oxidations of [Os(bpy)2L]" yield the corresponding low-spin Os species from which [Os(bpy)2L]+ can be regenerated." " [Ru(bpy)2L]" (HL = salicylic acid) has been prepared and structurally characterized as the tetrahydrate. Absorptions at 590 nm, 400 nm, and 290 nm in the electronic spectrum have been assigned to Ru bpy CT transitions electrochemical oxidations of the complex have been investigated." ... 

El. Kakemi, K., Arita, T., Yamashina, H., and Konishi, R., Absorption and excretion of drugs X. The effect of the protein binding on the renal excretion rate of salicylic acid derivatives. Yakugaku Zasshi 82, 536-639 (1962). 

SALSALATE (Saiicyisaiicyiic Acid) After absorption, the drug is partially hydrolyzed into two molecules of salicylic acid. Insoluble in gastric secretions, it is not absorbed until it reaches the small intestine. 

Absorption of Salicylic Acid. Excised oat roots absorbed salicylic acid in two distinct phases (Figure 1). Upon exposure to salicylic acid the root segments rapidly absorbed the eompound to attain a concentration of about 0.5 pmole/g of tissue. On the assumption that 1 g of tissue equals 1 mL of tissue, this translates to 0.5 mM salicylic acid inside the tissue, the same concentration as the external solution. This coneentration of salicylic acid was present in the tissue after 1 h and was maintained for over 3 h. By 4 h a second phase of absorption was evident (Figure 1). During the second phase, salicylic acid was absorbed at a greater rate that lasted for at least 24 h. At that time, enough salicylic acid had been absorbed that the eoncentration in the tissue was 8.0 mM. Thus, the tissue accumulated salicylic acid to concentrations greater than that in the external solution. An additional experiment (not shown) showed that the tissue would continue to absorb salicylic acid until the compound was depleted from the external solution. 

In Vivo Metabolism of Salicylic Acid. All the salicylic acid absorbed by the tfissue TFigure TT did not remain as that acid. Initially (< 2 h), most of it remained as such (Table II). However, gradually more parent compound was converted to a metabolite, so that between 4 and 20 h most of the absorbed salicylic acid was thus converted. At 20 h, 6.79 mole/g of metabolite was present in the tissue. Thus, the accumulation of "salicylic acid" observed in the absorption... 

Figure 1. Absorption of salicylic acid for 1 to 24 hr by excised oat roots.

An understanding of absorption, binding, metabolism, and excretion is more important for phenytoin than it is for most drugs. Following oral administration, phenytoin absorption is slow but usually complete, and it occurs primarily in the duodenum. Phenytoin is highly bound (about 90%) to plasma proteins, primarily plasma albumin. Since several other substances can also bind to albumin, phenytoin administration can displace (and be displaced by) such agents as thyroxine, triiodothyronine, valproic acid, sulfafurazole, and salicylic acid. 

Although aspirin itself is pharmacologically active, it is rapidly hydrolyzed to salicylic acid after its absorption, and it is the salicylate anion that accounts for most of the anti-inflammatory activity of the drug. The superior analgesic activity of aspirin compared with sodium salicylate implies that aspirin has an intrinsic activity that is not totally explainable by its conversion to salicylic acid. Aspirin inhibits COX-1 to a much greater extent than COX-2 sodium salicylate is more selective for COX-1. This, combined with the ability of aspirin to acetylate proteins, might account for some of the therapeutic and toxicological differences between aspirin and the other salicylates. 

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