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PubMed1978

Absorption and elimination of D-propoxyphene, acetyl salicylic acid, and phenazone in a combination tablet (Doleron): comparison between young and elderly subjects.

The single-dose kinetics of D-propoxyphene, acetyl salicylic acid and phenazone, given in a combination tablet (Doleron), were compared in young and elderly subjects. Serial blood samples were taken 0--48 hours after administration. The plasma concentrations of propoxyphene and of its major metabolite, norporpoxyphene, were assessed by mass fragmentography, those of phenazone by gas chromatography, and those of acetyl salicylic acid plus salicylic acid by spectrofluorometry. Neither for propoxyphene, norpropoxyphene, acetyl salicylic acid nor phenazone did the areas under the concentration curves or the elimination half-lives differ between young and elderly subjects. These data do not provide pharmacokinetic support for a general reduction of the Doleron dosage in elderly subjects.

Administration, Oral↗
PubMed2003

Apoptotic cell death in suspension cultures of Taxus cuspidata co-treated with salicylic acid and hydrogen peroxide.

Apoptotic cell death in suspension cultures of Taxus cuspidata induced by exogenous salicylic acid and/or H2O2 was investigated. H2O2 (0.012% v/v) alone changed the permeability of cell membrane while salicylic acid (0.375 mM) not only altered the permeability but also caused nuclei condensation and a small amount of nuclei fragments. The combined use of salicylic acid (0.375 mM) and H2O2 (0.012% v/v) changed the cell membrane permeability more significantly and nuclei fragments occurred in ca. 30% of the cells at 48 h. DNA ladders of 180 bp and oligopolymers, characteristics of the apoptotic cleavage of nuclei DNA, were observed by agar electrophoresis. These results show that exogenous salicylic acid and H2O2 could synergistically induce the apoptotic cell death of suspension cultures of Taxus cuspidata.

Apoptosis↗
PubMed1999

Percutaneous absorption of salicylic acid in man after topical administration of three different formulations.

OBJECTIVE: To determine the amount of drug which is absorbed during 1 day following topical application of three different preparations containing salicylic acid. METHODS: Ten grams of the formulations, either (a) Kerasaltrade mark 5% ointment, (b) salicylic acid 5% or (c) 10% in petrolatum, were administered consecutively to a 600-cm2 area on alternating sides of the back of healthy volunteers (n = 9). Thirty minutes after application, a skin area of 2.54 cm2 was stripped with D-Squametrade mark adhesive disks to determine the amount of salicylic acid in the stratum corneum. The entire application site was then covered by a thin gauze bandage and was not washed for the next 24 h. Urine was collected for 26 h following administration, hydrolyzed and assayed by HPLC analysis. RESULTS: The absolute amounts absorbed and excreted were 52.6 +/- 29.4 mg (mean +/- SD), 127.1 +/- 43.9 mg and 208.0 +/- 81.7 mg, and the doses absorbed in relation to the doses applied (500 mg salicylic acid in case of formulations a and b and 1,000 mg for formulation c) were 9.3 +/- 3.8, 25.1 +/- 8.5 and 20.2 +/- 7.7%, respectively. The amounts of salicylic acid in the skin 30 min after application were 36.3 +/- 16.5, 18.2 +/- 11.9 and 31.3 +/- 15.4 microg/ cm2 as determined by the tape stripping procedure. CONCLUSIONS: Significant differences in the doses absorbed were detected between the two formulations a and b (same concentration) with different vehicles (p value < 0.001) as well as between b and c (same vehicle) with different concentrations (p value = 0.018) using Student's paired t test. These results demonstrate that salicylic acid is well absorbed by healthy skin.

Administration, Cutaneous↗
PubMed2006

Effect of salicylic acid on invasion of human vascular endothelial cells by Staphylococcus aureus.

Invasion of vascular endothelial cells by Staphylococcus aureus is associated with diverse complications and recurrent infection. Little is known about the effect of salicylic acid, the major metabolite of aspirin, on the interaction between S. aureus and vascular endothelial cells. We examined the adhesion of S. aureus strain 8325-4 cultured with or without salicylic acid to human umbilical vein endothelial cells (HUVECs), and the ability of the strain to invade these cells. Strain 8325-4 cells grown in salicylic acid were significantly less adherent to and invasive in HUVECs. Production of cytokine interleukin (IL)-6 was lower from the HUVECs infected with clinical isolates of S. aureus cultured in salicylic acid compared with those unexposed to salicylic acid. This study raises the possibility of using salicylic acid as an adjuvant therapeutic agent in the treatment of S. aureus bacteremia to prevent its complications or recurrence.

Bacterial Adhesion↗
PubMed1984

Effect of systemic anaphylaxis on the absorption of salicylic acid from the rat small intestine.

Rats were immunized by intraperitoneal injection of ovalbumin (egg albumin) emulsified in Freund's incomplete adjuvant, and then the effect of an intravenous challenge with ovalbumin on salicylic acid absorption from the small intestine was examined by means of an in situ recirculation technique. The disappearance of salicylic acid from the luminal solution was significantly decreased in rats treated with ovalbumin compared with control groups treated with saline. The decreased absorption of salicylic acid in ovalbumin-immunized rats was related to the anti-ovalbumin antibody responses examined by passive cutaneous anaphylactic reactions. On the other hand, the decreased absorption of salicylic acid was not found in ovalbumin-immunized rats challenged intravenously with bovine gamma-globulin. Similar results were also noted in rats immunized via the footpads with ovalbumin. However, no significant change was observed in the intestinal absorption of salicylic acid in normal (nonimmunized) rats challenged intravenously with ovalbumin. Furthermore, intestinal absorption of sulfadimethoxine and sulfanilamide was significantly decreased during systemic anaphylaxis, whereas no change was observed in the absorption of sulfisoxazole, quinine, sulfanilic acid, and phenolsulfonphthalein. This suggests that the intestinal absorption of rapidly absorbed drugs, including salicylic acid, is more sensitive to systemic anaphylaxis than that of poorly absorbed drugs.

Anaphylaxis↗
PubMed1985

Acetylsalicylic acid and juvenile rheumatoid Arthritis. Effect of dosage interval on the serum salicylic acid level.

A 2-dose regimen and a 3-dose regimen, both with the same daily dose of acetylsalicylic acid, were compared in 8 patients with juvenile rheumatoid arthritis. The regimens were given according to a cross-over design. The serum salicylic acid levels over 24 hours were studied at the end of each treatment period. As expected somewhat greater fluctuations in the salicylic acid levels were observed with the 2-dose than with the 3-dose regimen. However, therapeutically effective serum levels were observed for most of the 24 hour period with both regimens. It is suggested that a 2-dose regimen has advantage with regard to simplicity and compliance. The pharmacokinetic findings indicate that a 2-dose regimen may be useful in patients with juvenile rheumatoid arthritis.

Adolescent↗
PubMed2005

Kinetic and safety assessment for salicylic acid nitration by nitric acid/acetic acid system.

The nitration process of salicylic acid for the production of the important intermediate 5-nitrosalicylic acid is studied from thermokinetic and safety points of view. Investigations carried out by considering, as process deviations, the loss of the thermal control point out the possibility of runaway phenomena due to the occurrence of polynitration reactions. Isothermal experiments are carried out in various conditions to assess the involved reaction network and reaction kinetics.

Acetic Acid↗
PubMedDate not supplied

Effects of topical petrolatum and salicylic acid upon skin photoreaction to UVA.

Various agents which can be used in combination can also interfere with phototherapy. In this study, the effects of topical petrolatum and 20% salicylic acid in petrolatum upon skin photoreaction to UVA were investigated, in an in vivo test. Minimal phototoxic dose (MPD) test was performed on 31 volunteers and the test was repeated with thin (0.1 cc/25 cm(2)) petrolatum, thick (0.3 cc/25 cm(2)) petrolatum, thin 20% salicylic acid in petrolatum, thick 20% salicylic acid in petrolatum and sunscreen. The effect of each agent on MPD was investigated. MPD was increased with thin and thick applications of all agents. Also, MPD was increased with 20% salicylic acid in petrolatum when compared with pure petrolatum, in the same thickness. The application of petrolatum and salicylic acid in petrolatum just before PUVA therapy is not recommended because of their blocking effects.

Administration, Topical↗
PubMed1995

Hydrogen Peroxide Stimulates Salicylic Acid Biosynthesis in Tobacco.

Hydrogen peroxide induced the accumulation of free benzoic acid (BA) and salicylic acid (SA) in tobacco (Nicotiana tabacum L. cv Xanthi-nc) leaves. Six hours after infiltration with 300 mM H2O2, the levels of BA and SA in leaves increased 5-fold over the levels detected in control leaves. The accumulation of BA and SA was preceded by the rapid activation of benzoic acid 2-hydroxylase (BA2H) in the H2O2-infiltrated tissues. This enzyme catalyzes the formation of SA from BA. Enzyme activation could be reproduced in vitro by addition of H2O2 or cumene hydroperoxide to the assay mixture. H2O2 was most effective in vitro when applied at 6 mM. In vitro activation of BA2H by peroxides was inhibited by the catalase inhibitor 3-amino-1,2,4-triazole. We suggest that H2O2 activates SA biosynthesis via two mechanisms. First, H2O2 stimulates BA2H activity directly or via the formation of its substrate, molecular oxygen, in a catalase-mediated reaction. Second, higher BA levels induce the accumulation of BA2H protein in the cells and provide more substrate for this enzyme.

Journal Article↗
PubMed2006

Salicylic acid reduces the production of several potential virulence factors of Pseudomonas aeruginosa associated with microbial keratitis.

PURPOSE: Pseudomonas aeruginosa is a common cause of contact-lens-related microbial keratitis. This bacterium is becoming increasingly resistant to antibiotics, and even if the infection can be treated with antibiotics, damage to the cornea resulting from the combined effect of bacteria and host factors can lead to loss of vision. The purpose of this study was to test the effect of salicylic acid on the production of potential virulence factors during the growth of P. aeruginosa. METHODS: Bacterial cells were grown in a subinhibitory concentration of salicylic acid, and supernatants were collected and analyzed for presence of proteases by using zymography and hydrolysis of chromogenic substrates. The supernatants were also analyzed for the amount of acetylated homoserine lactones by using bacterial reporter strains. Pseudomonas cells from salicylic acid cultures were analyzed for their twitching and swimming motility as well as their ability to invade or cause the death of corneal epithelial cells. RESULTS: Growth in a subinhibitory concentration of salicylic acid resulted in a significant reduction in the number of bacterial cells and a reduction in the rate of the number of bacteria increasing during logarithmic growth, but the time to reach the stationary phase of growth was unchanged. These changes in growth pattern affected the amount of acylated homoserine lactones produced by P. aeruginosa 6294. Also affected by growth in salicylic acid was the ability of strain 6294 to show twitching or swimming motility. Salicylic acid also reduced the invasion of strain 6294 into corneal epithelial cells and the epithelial cell death caused by strain 6206. Furthermore, production of proteases by P. aeruginosa was significantly reduced by growth in salicylic acid. CONCLUSIONS: The results of this study clearly demonstrate that salicylic acid has a significant impact on several potential virulence factors of P. aeruginosa that may be involved in the production of microbial keratitis. These effects were probably mediated by reduction in the cell density and concomitant reduction in the quorum-sensing signaling molecules, the acylated homoserine lactones, produced by P. aeruginosa.

4-Butyrolactone↗
PubMed1976

The effects of salicylic acid on metabolism and potassium ion content in yeast.

Under anaerobic conditions, at low pH and 30 degrees, commercial baker's yeast loses K+ ion in the presence of salicylic acid. Glucose utilization is inhibited. In suspensions containing no glucose, carbohydrate stores of the cell are dissimilated to carbon dioxide and alcohol. The ion loss and inhibitory effects of salicylic acid on glucose utilization are reversed by washing the cells free of salicylate. The loss of K+ appears to be due at least partly to a K+-H+ exchange process. An unexplained maximum is seen in the curves of either net K+ loss or K+ efflux versus salicylic acid concentration. At 6 degrees the effects of salicylic acid on both endogenous metabolism and net K+ loss are minimal. Furthermore, no maximum is seen in the K+ loss-salicyclic concentration curve at this temperature. It is generalized that salicylic acid or salicylate may elicit K+ leakage from many types of cells, i.e., a fundamental action of this compound may be its ability to affect (reduce) K+ content of the cell; furthermore, it appears that the salicylate effects on K+ loss may be associated in an as-yet-unknown manner with the metabolic effects of this compound. The effects of salicylate on K+ loss in yeast may not be unique for this compound, since no experiments of this nature have been done with other penetrating undissociated acids.

Carbohydrate Metabolism↗
PubMed2003

Capillary electrophoresis-based profiling and quantitation of total salicylic acid and related phenolics for analysis of early signaling in Arabidopsis disease resistance.

A capillary electrophoresis-based method for quantitation of total salicylic acid levels in Arabidopsis leaves was developed. Direct comparison to previous high-performance liquid chromatography (HPLC)-based measurements showed similar levels of salicylic acid. Simultaneous quantitation of trans-cinnamic acid, benzoic acid, sinapic acid, and an internal recovery standard was achieved. A rapid, streamlined protocol with requirements for plant tissue reduced relative to those of HPLC-based protocols is presented. Complicated, multiparameter experiments were thus possible despite the labor-intensive nature of inoculating plants with bacterial pathogens. As an example of this sort of experiment, detailed time course studies of total salicylic acid accumulation by wild-type Arabidopsis and two lines with mutations affecting salicylic acid accumulation in response to either of two avirulent bacterial strains were performed. Accumulation in the first 12h was biphasic. The first phase was partially SID2 and NDR1 dependent with both bacterial strains. The second phase was largely independent of both genes with bacteria carrying avrB, but dependent upon both genes with bacteria carrying avrRpt2. Virulent bacteria did not elicit salicylic acid accumulation at these time points. Application of this method to various Arabidopsis pathosystems and the wealth of available disease resistance signaling mutants will refine knowledge of disease resistance and associated signal transduction.

Arabidopsis↗
PubMed1984

In vivo absorption of theophylline and salicylic acid from rat small intestine.

In vivo absorption of theophylline and salicylic acid from the rat small intestine was studied by a closed segment technique. The drugs were administered at 1 and 4 mM in dissolved form, both in the presence and absence of phlorizin (0.01 mM). Drug concentrations were measured by high-pressure liquid chromatography. Phlorizin inhibited the absorption of theophylline (pKa = 8.6) at 4 mM but not at 1 mM. In contrast, the absorption of salicylic acid (pKa = 3) both at 1 and 4 mM was unaffected by phlorizin. This suggests that an active transport system, sensitive to phlorizin, is involved in the rat intestinal absorption of theophylline, but not in that of salicylic acid. Apart from differences in drug structure, differences in the degree of ionization may influence the access of acidic drugs to this transport system.

Animals↗
PubMed1983

[Distribution of salicylic acid and hydrolysis of acetylsalicylic acid in the human fetus in early pregnancy].

The materno-fetal transfer of salicylic acid and its distribution in the fetal organism was investigated in women of early pregnancy. Acetylsalicylic acid (Acesal) was administered orally in a single dose or in repeated doses at different times before legal interruption. The mean passage rates were about 6-15%. They were independent of the maternal serum concentrations of salicylic acid. The distribution of salicylic acid on the fetal liver, intestine, kidneys, lungs and brain was different. All fetal organs (9th to 15th week of gestation) studied exhibit an acetylsalicylic acid-splitting esterase activity. The esterase activity of the fetal liver was about 30% of the hydrolytic activity of the adult liver. The esterase activity was mainly located in the 105 000 X g-supernatant of cell homogenates.

Aspirin↗
PubMed1984

A simple fluorometric method for the determination of salicylic acid in aluminium acetylsalicylate.

A simple, rapid fluorometric method for the determination of salicylic acid in aluminium acetylsalicylate is presented. The method is based on the dissolution of aluminium acetylsalicylate in sodium fluoride-hydrochloric acid solution, filtration and dilution with buffer solution pH = 4 followed by the fluorometric determination of the liberated salicylic acid. The method was applied successfully to the determination of salicylic acid in aluminium acetylsalicylate tablets.

Aspirin↗
PubMed2004

Solubility and phase separation of benzocaine and salicylic acid in 1,4-dioxane-water mixtures at several temperatures.

The solubilities of benzocaine and salicylic acid were determined in water-dioxane mixtures at several temperatures (5-40 degrees C for benzocaine and 10-40 degrees C for salicylic acid). The solubility curves as a function of dioxane ratio showed a maximum at 90% dioxane at all temperatures. Above 25 degrees C, the homogeneous mixture splits into two liquid immiscible phases. For benzocaine, the initial dioxane concentration range at which phase separation takes place increased with temperature (50-60% at 25 degrees C, 50-70% at 30-35 degrees C and 40-70% at 40 degrees C). For salicylic acid, the dioxane concentration required for phase separation (40-60% dioxane) did not change with temperature. Phase separation was not related to solid phase changes (polymorphism or solvates). The phase composition and drug extraction at the drug-rich phase were determined. The apparent enthalpies of the solution process were a nonlinear function of the dioxane ratio for both drugs. The apparent enthalpy of solution of benzocaine was larger than that expected at the upper limit of phase separation (70% dioxane), whereas for salicylic acid the apparent enthalpy of solution decreased abruptly at the region corresponding to phase separation (40-70% dioxane). Both drugs showed a nonlinear pattern of enthalpy-entropy compensation.

Benzocaine↗
PubMed2005

Kinetics of salicylic acid adsorption on activated carbon.

The adsorption and desorption of salicylic acid from water solutions was investigated in HPLC microcolumns packed with activated carbon. The adsorption isotherm was obtained by the step-up frontal analysis method in a concentration range of 0-400 mg/L and was well fitted with the Langmuir equation. The investigation of rate aspects of salicylic acid adsorption was based on adsorption/desorption column experiments where different inlet concentrations of salicylic acid were applied in the adsorption phase and desorption was conducted with pure water. The concentration profiles of individual adsorption/desorption cycles data were fitted using several single-parameter models of the fixed-bed adsorption to assess the influence of different phenomena on the column behavior. It was found that the effects of axial dispersion and extraparticle mass transfer were negligible. A rate-determining factor of fixed-bed column dynamics was the kinetics of pore surface adsorption. A bimodal kinetic model reflecting the heterogeneous character of adsorbent pores was verified by a simultaneous fit of the column outlet concentration in four adsorption/desorption cycles. The fitted parameters were the fraction of mesopores and the adsorption rate constants in micropores and mesopores, respectively. It was shown that the former rate constant was an intrinsic one whereas the latter one was an apparent value due to the effects of pore blocking and diffusional hindrances in the micropores.

Journal Article↗