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PubMed2005

Case studies: Use of salicylic acid (Avosil) and hydrogel (Avogel) in limiting scar formation.

OBJECTIVE: The purpose of this report is to present the results of a preliminary treatment regimen for hypertrophic scars combining topical 2% salicylic acid cream (Avosil) with an overlay of hydrogel dressing (Avogel). METHODS: The study group consisted of 3 patients with symptomatic hypertrophic scars: 2 presternal and 1 on the inner thigh. Scars were divided into 3 equal-size areas: (1) untreated control, (2) hydrogel alone, and (3) 2% salicylic acid with hydrogel cover. Treatments were applied every 8 to 12 hours and a Velcro appliance was employed to cover the area during treatment. The total length of treatment was 60 days. RESULTS: At the end of the 60-day treatment protocol, the area treated with 2% salicylic acid and hydrogel was asymptomatic. In contrast, the hydrogel-treated and untreated control areas remained erythematous and symptomatic for burning pain and pruritus. CONCLUSION: This small study suggests the efficacy of combined salicylic acid and hydrogel therapy in the treatment of hypertrophic scars. More extensive studies of scar treatment with salicylic acid and hydrogel are needed. These studies must be larger in scope to carefully document the spectrum of patient responses and should include methods for evaluating alterations in the levels of different inflammatory mediators.

Case Reports↗
PubMed1980

Rapid determination of indomethacin and salicylic acid in serum by means of reversed-phase liquid chromatography.

A method for the quantitative analysis of indomethacin and salicylic acid in blood serum and urine by high-performance liquid chromatography is described. A C18-bonded silica was used as the stationary phase and mixtures of ethanol, n-butanol and aqueous buffer as the mobile phase. Before injection the serum is deproteinized and extracted in one step. The recovery of the extraction was found to be 88% and 77% for indomethacin and salicylic acid, respectively. The relative standard deviations of the analysis for 0.5 micrograms indomethacin and 5 micrograms salicyclic acid per ml serum were 3.6% and 3.2%, respectively. The detection limits for indomethacin and salicylic acid were 2 ng. This corresponds for both substances to 0.1 micrograms/ml serum for an injection volume of 100 microliters. The method enables simultaneous determination of possibly formed metabolites. A number of concurrently administered drugs do not interfere with the analysis. The interactive effects of co-medication of indomethacin and salicylic acid on the serum concentration of indomethacin is demonstrated by measuring the pharmacokinetic curves.

Arthritis, Rheumatoid↗
PubMed1990

Sex differences in salicylic acid metabolism in streptozotocin induced diabetes in rats.

The metabolism of salicylic acid was studied in male and female streptozotocin-induced diabetic Wistar rats. Results obtained showed that in both sexes there was a significant increase in urinary excretion of salicyluric acid in diabetic rats when compared to controls (P less than or equal to 0.001). Within the diabetic groups, there was a significant increase in the urinary excretion of salicyluric acid in the female in comparison to the male rats (P less than or equal to 0.01). A statistically significant increase was observed in urinary excretion of salicyl-glucuronic acid in diabetic female compared to control female rats (P less than or equal to 0.01) while comparison of diabetic male to control male showed a significant decrease in urinary excretion of salicyl-glucuronic acid (P less than or equal to 0.01). Comparison of the diabetic female and male groups showed a high statistically significant difference in urinary excretion of salicyl-glucuronic acid. The diabetic ration, ie diabetic/control was significantly higher in female than in male rats with respect to salicyl-glucuronic acid (P less than or equal to 0.001) and total urinary excretion (P less than or equal to 0.01). The diabetic ratio may likely reflect the true significance of the roles played by the two metabolic pathways. The results suggest sex differences in the metabolism of salicylic acid; this may also be the case in other disease states.

Animals↗
PubMedDate not supplied

Effects of age and dose on disposition and metabolism of salicylic acid in male Fischer 344 rats.

Salicylic acid (SAL)-induced nephrotoxicity has been reported to be greater in older rats. To examine age- and dose-related changes in disposition and metabolism, male Fischer 344 rats aged 3, 12, and 25 months were administered single doses of 14C-SAL at 5,50, and 500 mg/kg po. At 5 mg 14C-SAL/kg, urinary excretion of 14C-SAL derived radioactivity (RA) followed first-order kinetics and was complete by 24 hr in 3- and 25-month-old rats, but not until 48 hr in 12-month-old rats. The percentage of administered 14C-SAL excreted as the oxidative metabolites 2,3- and 2,5-dihydroxybenzoic acid (2,3- and 2,5-diOH), unmetabolized SAL, or salicyl ester glucuronide (SA-AG) was unchanged with age. The percentage excreted as the ether glucuronide (SA-PC) was significantly decreased in 25-month-old rats, while the percentage excreted as the glycine conjugate, salicyluric acid (SUA) was significantly increased in 12- and 25-month-old rats. At 50 mg SAL/kg, urinary elimination shifted toward zero-order kinetics and was not complete until 48 hr in all age groups. The percentage of an administered dose of 14C-SAL found in urine as 2,3- and 2,5-diOH and SA-AG increased significantly in all age groups, while the percentage excreted as SUA decreased significantly. Twelve- and 25-month-old rats excreted a significantly greater percentage of the total dose as 2,3- and 2,5-diOH than 3-month-old rats at this dose. No SA-PG was detected at this dose in any age group. At 500 mg SAL/kg, mortality was observed in both 3- and 25-month-old rats and excretion of SAL-derived RA in urine was incomplete at 48 hr. However, data indicated a further shift in biotransformation toward increased production of oxidative metabolites and a decrease in SUA production. No significant overall differences were observed between 3- and 25-month-old rats in plasma levels of 14C-SAL following iv administration of 5 and 50 mg SAL/kg. However, elimination half-life (t1/2) was significantly increased in 25-month-old rats at 5 mg SAL/kg vs. 3-month-old rats. These results indicate that the age-related increase in acute nephrotoxicity of SAL may result from increased production of oxidative metabolites in older rats at higher doses of SAL.

Aging↗
PubMedDate not supplied

[Percutaneous resorption of salicylic acid methylester from bathing solutions].

Skin uptake of salicylic acid methylester (SAM) by bathing in PERNIONIN -Teilbad (Krewel-Werke, Eitorf) and KNEIPP-Wacholderölbad (Kneipp-Werke, Würzburg) was researched with pigs and human volunteers. In plasma, no SAM was found, only salicylic acid (SA) and traces of salicyluric acid (SU). Skin uptake increased after every new application in 2 h. About 30 mg SAM permeated through an area of pig's skin of 300 cm2 in this time. Plasma levels after whole body bathing of man with PERNIONIN at 36 degrees C were about 0.63 micrograms/g and with Wacholderölbad about 0.37 microgram/g SA. With Wacholderölbad at 38-42 degrees C plasma levels increased to about 1 micrograms/g SA. In 24 h after bathing at 36 degrees C 329 and 304 mg SU were eliminated in urine and after bathing at 38-42 degrees C only 17.8 mg SU. From these SAM baths we found maximal plasma levels of SS in contrast to any other topical applied SS drug. Tissue levels from the application area were higher than the systemic concentration. SAM bathing is one of the most effective methods of local SS application in rheumatology.

Animals↗
PubMedDate not supplied

Determination of aspirin and salicylic acid by reverse-phase liquid chromatography.

Buffered solid dosage forms containing aspirin, magnesium hydroxide, and aluminum hydroxide are blended with acidic ethanol to extract the aspirin and salicylic acid rapidly. The resulting preparation is then immediately injected onto a 4.6 mm x 3 cm 5 micron reverse-phase column. Aspirin and free salicylic acid are determined simultaneously. The run time is less than 2 min. The total time from the initiation of sample extraction to completion of the separation is less than 5 min.

Aspirin↗
PubMed1989

[Study on transdermal absorption of borneol-salicylic acid eutectic mixture].

Borneol is an organic drug having property to form eutectic mixture with salicylic acid. We compared the transdermal absorption rate of borneol alone with that of borneol-salicylic acid eutectic mixture in hairless rats. The results showed that the borneol-salicylic acid eutectic mixture can evidently increase the absorption rate of borneol and provided a method for manufacturing borneol preparation which can easily be absorbed transdermally.

Animals↗
PubMedDate not supplied

Infrared spectroscopic characterization of the interaction of lipid bilayers with phenol, salicylic acid and o-acetylsalicylic acid.

The interaction of phenol (PHE), salicylic acid (SA) and o-acetylsalicylic acid (ASA) with bilayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was investigated by infrared spectrometry. The temperature of the main gel to liquid crystal phase transition of DPPC is markedly depressed in the presence of the three guest molecules. The temperature depression depends on the nature and concentration of the additives. The temperature of the pretransition is also affected by these guest molecules and the depression in temperature is even more pronounced than that of the main transition temperature. Possible modes of interaction of these guest molecules with the lipid bilayers are discussed.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

Distribution and keratolytic effect of salicylic acid and urea in human skin.

Salicylic acid (SA) and urea are widely used in topical preparations. Using a simple tape stripping technique the effect on the binding forces within the stratum corneum and the skin absorption of SA and urea were studied. The degree of stratum corneum removal was recorded by measuring the transmission through the tape with a digital light-measuring instrument. With successive stripping of the skin the amount of tissue adhering to the tape decreased. Exposure of the upper arm to 2% SA for 6 h increased the skin material on the tape strips significantly. No significant increase was recorded after 3-hour exposure, or after exposure to 0.5% SA. Neither did the exposure to 10% urea for 3 or 6 h influence the amount of skin adhering to the tape significantly. Radiochemical analyses showed that the amount of SA and urea in each of the first 6 tape strips was about 5-15 micrograms/cm2. This technique provides a useful tool to evaluate the binding forces within the stratum corneum in relation to absorption of topically applied substances.

Administration, Topical↗
PubMed1975

Binding of 14-C-salicylic acid and 14-C-pentobarbital to plasma proteins of several species during the perinatal period.

The fraction binding of 14-C-salicylic acid and 14-C-pentobarbital was studied as a function of age in plasma of the pig, dog, goat and human. The pig exhibited an unusual degree of hypoalbuminemia and low fractional binding of salicylic acid at birth. Albumin levels and the percent binding of the salicylic acid were not significantly lower in newborn plasma than in adult plasma of the other species studied. The pig was also exceptional in that the high fractional binding of pentobarbital observed at low ligand concentrations in plasma of the newborn was not observed in the other species studied. Depletion of albumin in newborn pig plasma did not appreciably affect the binding of pentobarbital. Thus it is suggested that the plasma of the fetal and newborn pig may contain a nonalbuminoid protein, such as fetal globulin, which is capable of binding pentobarbital but does not have a high avidity for salicylic acid. It apparently does not exist at birth in the plasmas of the other species studied, as depletion of albumin markedly reduced the fractional binding of pentobarbital.

Age Factors↗
PubMedDate not supplied

Possible genetic influence on conjugate formation in salicylic acid metabolism.

Subjects (7 males and 7 females) were dosed with salicylic acid (1 g) and hourly urinary samples were analyzed for its metabolites. The results obtained showed that the female subjects had higher capacity for salicylurate formation than the male (P less than or equal to 0.025). The urinary hourly excretion ratio of salicylurate and salicylglucuronic acid was about or greater than 1 while in the male this ratio is less than 0.50. A comparison of this ratio between female and male showed a highly significant difference (P less than or equal to 0.001). The high capacity of glucuronic acid pathway in male and the alternate pathway in female suggest a possible genetic influence in salicylic acid metabolism.

Black People↗
PubMed2003

Fast and single solid phase fluorescence spectroscopic batch procedure for (acetyl) salicylic acid determination in drug formulations.

A solid phase fluorescence spectroscopic batch procedure for (acetyl) salicylic acid in drug formulations have been developed. The procedure is based on the sorption of salicylic acid (SA) on Sephadex DEAE A-25 anion exchanger gel (100 mg) by equilibration from an aqueous solution (10 or 25 ml) for 5 min; the equilibrated gel is transferred into an 1 mm quartz cell and the native fluorescence of SA sorbed on it is directly measured (lambda(ex)=297 nm; lambda(em)=405 nm). Good linearity was found in the 10-200 and 5-100 microg l(-1) ranges (for 10 and 25 ml sample volume, respectively) with R.S.D. (%) of 2.8 and 1.1. The procedure was successfully applied to the determination of acetyl salicylic acid (ASA) in drug formulations after alkaline hydrolysis to yield SA.

Algorithms↗
PubMed2000

Mutational analysis of a role for salicylic acid in iron metabolism of Mycobacterium smegmatis.

The role of salicylic acid in iron metabolism was examined in two wild-type strains (mc(2)155 and NCIMB 8548) and three mutant strains (mc(2)1292 [lacking exochelin], SM3 [lacking iron-dependent repressor protein IdeR] and S99 [a salicylate-requiring auxotroph derived in this study]) of Mycobacterium smegmatis. Synthesis of salicylate in SM3 was derepressed even in the presence of iron, as was synthesis of the siderophores exochelin, mycobactin, and carboxymycobactin. S99 was dependent on salicylate for growth and failed to grow with the three ferrisiderophores, suggesting that salicylate fulfills an additional function(s) other than being a precursor of mycobactin and carboxymycobactin. Salicylic acid at 100 microgram/ml repressed the formation of a 29-kDa cell envelope protein (putative exochelin receptor protein) in S99 grown both iron deficiently and iron sufficiently. In contrast, synthesis of this protein was affected only under iron-limited conditions in the parent strain, mc(2)155, and remained unaltered in SM3, suggesting an interaction between the IdeR protein and salicylate. Thus, salicylate may also function as a signal molecule for recognition of cellular iron status. Growth of all strains and mutants with p-aminosalicylate (PAS) at 100 microgram/ml increased salicylate accumulation between three- and eightfold under both iron-limited and iron-sufficient growth conditions and decreased mycobactin accumulation by 40 to 80% but increased carboxymycobactin accumulation by 50 to 55%. Thus, although PAS inhibited salicylate conversion to mycobactin, presumptively by blocking salicylate AMP kinase, PAS also interferes with the additional functions of salicylate, as its effect was heightened in S99 when the salicylate concentration was minimal.

Chromatography, High Pressure Liquid↗
PubMed1996

Coordinated activation of as-1-type elements and a tobacco glutathione S-transferase gene by auxins, salicylic acid, methyl-jasmonate and hydrogen peroxide.

The molecular mechanism of signal transduction pathways which mediate the action of phytohormones are poorly understood. Recently, we and others have shown that the as -1 type cis-acting elements can respond to auxin and salicylic acid, two well-characterized signaling molecules in plants. In the present work, we have examined a comprehensive set of physiological and abiotic agents and found that auxin, salicylic acid and methyl-jasmonate are three effective inducers of the as-1-type elements in transgenic tobacco. Using a cell suspension culture containing a synthetic promoter-GUS fusion, we demonstrated rapid and sensitive induction of the as-1-type element by these phytohormones. Furthermore, a tobacco glutathione S-transferase gene, GNT35, that contains an as-1-type binding site in its promoter is also inducible by auxin, salicylic acid and methyl-jasmonate with similar kinetics. As Ulmasov et al. have recently reported, we found that the as-1-type elements can also respond to weak/inactive analogues of auxin and salicylic acid. In addition, we show that hydrogen peroxide can also effectively activate the expression of GNT35 as well as the as-1-type element in a cell suspension culture, but not with whole seedlings. These results are discussed with respect to the possible mechanism(s) through which a single cis element may respond to a diverse array of molecules.

Acetates↗
PubMed2002

Salicylic acid reverses phorbol 12-myristate-13-acetate (PMA)- and tumor necrosis factor alpha (TNFalpha)-induced insulin receptor substrate 1 (IRS1) serine 307 phosphorylation and insulin resistance in human embryonic kidney 293 (HEK293) cells.

Salicylates, including aspirin, have been shown to improve insulin sensitivity both in human and animal models. Although it has been suggested that salicylates sensitize insulin action by inhibiting IkappaB kinase beta (IKKbeta), the detailed mechanisms remain unclear. Protein kinase C isoforms and tumor necrosis factor alpha (TNFalpha) signaling pathways are well described mediators of insulin resistance; they are implicated in the activation of IKKbeta and the subsequent inhibition of proximal insulin signaling via insulin receptor substrate 1 (IRS1) and Akt. This study investigated the effect of salicylic acid on phorbol 12-myristate 13-acetate (PMA)- and TNFalpha-induced insulin resistance in a human embryonic kidney 293 (HEK293) cell line stably expressing recombinant human IRS1. The results showed that both PMA and TNFalpha inhibited insulin-induced Akt phosphorylation and promoted IRS1 phosphorylation on Ser-307. Salicylic acid pretreatment completely reversed the effects of PMA and TNFalpha on both Akt and IRS1. Whereas PMA activated protein kinase C isoforms and IKKbeta, TNFalpha activated neither. On the other hand, both PMA and TNFalpha activated the c-Jun N-terminal kinase (JNK), which has been reported to directly phosphorylate IRS1 Ser-307. SP600125, a JNK inhibitor, prevented PMA and TNFalpha-induced IRS1 Ser-307 phosphorylation. Finally, salicylic acid inhibited JNK activation induced by both PMA and TNFalpha. Taken together, these observations suggest that salicylic acid can reverse the inhibitory effects of TNFalpha on insulin signaling via an IKKbeta-independent mechanism(s), potentially involving the inhibition of JNK activation. The role of JNK in salicylic acid-mediated insulin sensitization, however, requires further validation because the JNK inhibitor SP600125 appears to have other nonspecific activity in addition to inhibiting JNK activity.

Animals↗
PubMedDate not supplied

Further observations on the disposition characteristics of salicylic acid in analbuminemic rats.

The disposition characteristics of salicylic acid (SA) were investigated in analbuminemic rats after intravenous bolus injection of 10 and 173 mg kg-1 of SA to study the effects of plasma protein binding on drug disposition. Following the administration of 10 mg kg-1 of SA, total body SA clearance (CL) was markedly faster and its apparent volume of distribution (Vd) significantly greater in the analbuminemic rats in comparison to the controls. Further, the apparent elimination rate constant (kj) was two-fold greater and the corresponding elimination half-life (t 1/2) shorter in the rats with low plasma albumin. Whole body autoradiograms obtained following the administration of 14C-salicylic acid demonstrated that the tissue distribution of SA was greater in the analbuminemic rats which was in agreement with the larger Vd observed in this group of rats. After the administration of 173 mg kg-1 of SA, no differences in CL, Vd, kk or t 1/2 were noted between the analbuminemic and control rats. Dose-dependent SA disposition was observed in both the analbuminemic and control rats with the effects being more pronounced in the rats with low plasma albumin. The results suggested that the disposition characteristics of SA were markedly altered in the presence of low plasma albumin concentrations due to reduced plasma SA protein binding.

Animals↗
PubMed1996

Ozone-induced responses in Arabidopsis thaliana: the role of salicylic acid in the accumulation of defense-related transcripts and induced resistance.

Exposure of Arabidopsis thaliana to ozone results in the expression of a number of defense-related genes that are also induced during a hypersensitive response. A potential common link between the activation of defense gene expression during a hypersensitive response and by ozone treatment is the production of active oxygen species and the accumulation of hydrogen peroxide. Here we report that salicylic acid accumulation, which can be induced by hydrogen peroxide and is required for the expression of both a hypersensitive response and systemic acquired resistance, is also required for the induction of some, but not all, ozone-induced mRNAs examined. In addition, we show that ozone exposure triggers induced resistance of A. thaliana to infection with virulent phytopathogenic Pseudomonas syringae strains. Infection of transgenic plants expressing salicylate hydroxylase, which prevents the accumulation of salicylic acid, or npr1 mutant plants, which are defective in the expression of systemic acquired resistance at a step downstream of salicylic acid, demonstrated that the signaling pathway activated during ozone-induced resistance overlaps with the systemic acquired resistance activation pathway and is salicylic acid dependent. Interestingly, plants expressing salicylate hydroxylase exhibited increased sensitivity to ozone exposure. These results demonstrate that ozone activates at least two distinct signaling pathways, including a salicylic acid dependent pathway previously shown to be associated with the activation of pathogen defense reactions, and that this latter pathway also induces a protective response to ozone.

Arabidopsis↗