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Cytochrome and Alternative Pathway Respiration in Tobacco (Effects of Salicylic Acid).

In suspension cultures of NT1 tobacco (Nicotiana tabacum L. cv Bright Yellow) cells the cytochrome pathway capacity increased between d 3 and d 4 following subculturing and reached the highest level observed on d 7. The capacity decreased significantly by d 10 and was at the same level on d 14. Both alternative pathway capacity and the amount of the 35-kD alternative oxidase protein increased significantly between d 5 and d 6, reached the highest point observed on d 7, remained constant until d 10, and decreased by d 14. The highest capacities of the alternative and cytochrome pathways and the highest amount of the 35-kD protein were attained on the day that cell cultures reached a stationary phase of growth. Addition of salicylic acid to cell cultures on d 4 caused a significant increase in alternative pathway capacity and a dramatic accumulation of the 35-kD protein by 12 h. The alternative pathway capacity and the protein level reached the highest level observed by 16 h after salicylic acid addition, and the cytochrome pathway capacity was at about the same level at each time point. The accumulation of the 35-kD alternative oxidase protein was significantly decreased by addition of actinomycin D 1 h before salicylic acid and was blocked by addition of cycloheximide. These results indicate that de novo transcription and translation were necessary for salicylic acid to cause the maximum accumulation of the 35-kD protein.

Journal Article↗

Reduction of postischaemic ventricular dysfunction and arrhythmias by trapping hydroxyl radicals with salicylic acid.

Recent studies have suggested the ability of salicylic acid (SA) to trap the hydroxyl radicals (.OH) generated in reperfused ischaemic myocardium. This study was designed to examine the effect of SA on reperfusion-induced arrhythmias and postischaemic ventricular dysfunction. Isolated rat hearts perfused by the Langendorff technique were preperfused with SA for 10 min. Hearts were then made ischaemic for 30 min, followed by 30 min of reperfusion. The left-ventricular contractile functions, including left-ventricular developed pressure (LVDP) and its first derivative (LV dp/dt), and creatine kinase (CK) release, were determined before and after ischaemia. Epicardial electrocardiograms (ECG) were also employed to analyse the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF). SA improved LVDP and LV dp/dt, and reduced CK release, as compared to the control group (p < 0.05). The incidence of VT and VF during reperfusion was also significantly reduced by SA (p < 0.05). Analysis of tissue thiobarbituric acid-reactive products indicates that SA decreased oxidative stress during reperfusion. In conclusion, these results suggest that SA reduces ventricular dysfunction and attenuates ventricular arrhythmias by trapping OH radicals upon reperfusion in isolated rat hearts.

Animals↗

Role of salicylic acid in tomato defense against cotton bollworm, Helicoverpa armigera Hubner.

We investigated the role of the salicylic acid (SA) signaling pathway in defense responses of tomato plants to the herbivore, cotton bollworm. After exposure to the cotton bollworm, tomato leaves rapidly accumulated a high level of SA. The transcription of PR1 and BGL2 genes, the marker genes of SA pathway, was up-regulated. An enhanced endogenous SA level was accompanied by an increase in the endogenous H2O2 level as compared with controls. Spraying tomato plants with a solution containing either SA or methyl salicylic acid (Me-SA), the H2O2 level dramatically increased. These data proved that the SA pathway was involved in the tomato plant defense responses to the herbivore.

Animals↗

Salicylic acid prevents the adherence of bacteria and yeast to silastic catheters.

During the pathogenesis of catheter-related urinary tract infection, bacteria attach to the catheter and migrate along a biofilm into the bladder. We studied the effect of coating silastic catheters with salicylic acid on bacterial and yeast adherence. An agar roll technique, bioluminescent assay, and radiolabeling study all produced consistent results. There was a dose related inhibition of adherence with Pseudomonas aeruginosa, Enterobacter aerogenes, Klebsiella pneumoniae, Candida albicans, and Enterococcus faecalis. Inhibition of over 90% was noted with Enterobacter and Pseudomonas. Similar results were obtained in broth and synthetic urine. A dose related reduction in adherence was seen with all gram-negative rods and yeast as measured by a radiolabeling assay. TDMAC was used to bind the salicylic acid to the catheters with > 95% inhibition of the gram-negative rods. These studies suggest the potential role of coating catheters with salicylic acid to reduce bacterial adherence and urinary tract infection.

Bacterial Adhesion↗

Studies on the reactivity of acyl glucuronides--VII. Salicyl acyl glucuronide reactivity in vitro and covalent binding of salicylic acid to plasma protein of humans taking aspirin.

Salicyl acyl glucuronide (SAG) is a significant metabolite of salicylic acid (SA) and aspirin. We have shown that, under physiological conditions in vitro, SAG undergoes rearrangement in a manner consistent with acyl migration to its 2-, 3- and 4-O-acyl positional isomers as the predominant pathway (T1/2 values were 1.4-1.7 hr in buffer at pH 7.4 and 37 degrees). Incubation of SAG or a mixture of its rearrangement isomers (iso-SAG) (each at approximately 50 micrograms SA equivalents/mL) with human serum albumin (HSA, at approximately 40 mg/mL) revealed the formation of covalent adducts with the protein, with peak concentrations of 1-2 micrograms SA equivalents/mL. The data support a role for the rearrangement/glycation mechanism of adduct formation. Covalent adducts of SA were also detected in the plasma of humans taking aspirin (at > or = 1200 mg/day), but the concentrations were low (<< 100 ng SA equivalents/mL). Reactivity of SAG thus provides a mechanism (though of uncertain quantitative importance) of covalent attachment of the salicyl moiety of aspirin to tissue macromolecules, which is in addition to its well-known acetylating capacity.

Animals↗

Evidence against specific binding of salicylic acid to plant catalase.

It was demonstrated that salicylic acid (SA) not only binds to catalase from differentiated higher plants and plant cell suspension cultures but also to those of fungi and animals. SA bound specifically to iron-containing enzymes, such as catalase, aconitase, lipoxidase and peroxidase, while not to iron-free plant enzymes. On the grounds of these experiments, the claim is further challenged that SA is a signalling compound and second messenger in plants that activates plant defense-related genes through elevated H2O2 levels by specifically inhibiting catalase activity. SA may just function as a phytoalexin.

Aconitate Hydratase↗

Salicylic acid enhances Jaceosidin and Syringin production in cell cultures of Saussurea medusa.

Addition of 20 muM salicylic acid to Saussurea medusa cell cultures at day 6 resulted in jaceosidin and syringin productions up to 95 mg l(-1 )and 631 mg l(-1) which were, respectively, about 2.5- and 2.7-fold higher than in the control. The biomass was increased from 8 to 12 g l(-1). Expression of chalcone synthase gene (chs) increased sharply after 12 h treatment and was sustained up to 48 h; chalcone isomerase gene (chi) expression reached a peak at 24 h and decreased after 48 h; and phenylalanine ammonia-lyase activity increased by 7.5-fold (96 U mg(-1) protein) higher than in the control after 24 h. These results indicate that salicylic acid enhances the production of jaceosidin and syringin which is accompanied by induction of the related phenylpropanoid biosynthetic enzymes.

Cell Culture Techniques↗

Treatment of androgenetic alopecia in females in reproductive age with topical estradiolbenzoate, prednisolon and salicylic acid.

INTRODUCTION: Women generally regard their hair loss as socially unacceptable; it is a stressful condition that considerably undermines their self-image and can even be the basis for psychologic disorders. AIM: The aim of the present study was to evaluate the efficacy and safety of topical treatment of androgenetic alopecia (AGA) with estradiolbenzoate, prednisolon and salicylic acid solution (EPS) in females. MATERIAL AND METHODS: An open trial with topical solution containing estradiolbenzoate, prednisolon and salicylic acid was performed in females suffering from AGA. Forty five female patients aged 18 to 42 years were enrolled in a 32-week trial. Forty two of the patients completed the trial. The mean nonvellus hair count taken within 1 cm2 in one and the same area was used to assess the treatment effect. RESULTS: At the end of the trial 59.52% +/- 7.57% of the patients had no hair regrowth, 33.33% +/- %7.27% presented with minimal and 7.14% +/- 3.97% moderate hair growth. The mean count of nonvellus hair increased with 15.79 +/- 1.35. The treated patients showed no significant adverse effects. CONCLUSION: Topical solution of estradiolbenzoate, prednisolon and salicylic acid is an efficacious and safety treatment of androgenetic alopecia in females.

Administration, Topical↗

Salicylic acid alleviates the cadmium toxicity in barley seedlings.

Salicylic acid (SA) plays a key role in plant disease resistance and hypersensitive cell death but is also implicated in hardening responses to abiotic stressors. Cadmium (Cd) exposure increased the free SA contents of barley (Hordeum vulgare) roots by a factor of about 2. Cultivation of dry barley caryopses presoaked in SA-containing solution for only 6 h or single transient addition of SA at a 0.5 mM concentration to the hydroponics solution partially protected the seedlings from Cd toxicity during the following growth period. Both SA treatments had little effect on growth in the absence of Cd, but increased root and shoot length and fresh and dry weight and inhibited lipid peroxidation in roots, as indicated by malondialdehyde contents, in the presence of Cd. To test whether this protection was due to up-regulation of antioxidant enzymes, activities and transcript levels of the H(2)O(2)-metabolizing enzymes such as catalase and ascorbate peroxidase were measured in control and SA-treated seedlings in the presence or absence of 25 microM Cd. Cd stress increased the activity of these enzymes by variable extent. SA treatments strongly or completely suppressed the Cd-induced up-regulation of the antioxidant enzyme activities. Slices from leaves treated with SA for 24 h also showed an increased level of tolerance toward high Cd concentrations as indicated by chlorophyll a fluorescence parameters. The results support the conclusion that SA alleviates Cd toxicity not at the level of antioxidant defense but by affecting other mechanisms of Cd detoxification.

Adaptation, Physiological↗

Role of Hydrophobic Effect on the Noncovalent Interactions Between Salicylic Acid and a Series of beta-Cyclodextrins.

The molecular complexation of salicylic acid (o-hydroxybenzoic acid) by beta-cyclodextrin (beta-CD) and/or two of its most used derivatives, 2,6-di-O-methyl-beta-cyclodextrin (DIMEB) and hydroxypropyl-beta-cyclodextrin (HPBCD), was studied from pH potentiometric measurements. The role of the hydrophobic effect was evaluated by studying the influence of the presence of different constant amounts of a series of alcohols (methanol, ethanol, propanol, and butanol) on the CD:guest interaction at 25 degrees C. The study was carried out by measuring the pH of the hydroalcoholic solutions of the guest, whose concentration is kept constant, as a function of cyclodextrin concentration. The dissociation constant of salicylic acid and the binding constants of the inclusion complexes formed by the CD and both the nonionized (HSA) and ionized (SA-) forms of the guest were simultaneously determined at all alcohol concentrations by using a model previously derived by us. The carboxylic forms were found to bind the CD with higher affinities than the carboxylate partners, irrespective of the polarity of the medium and the cyclodextrin used. The ratio KCD:HSA/KCD:SA- is a constant value characteristic of the cyclodextrin, which points to the hydrophobic effect as one of the main forces involved in the association. A clear influence of the solvent polarity on the affinity of binding was found, in the sense that, as long as the medium becomes more apolar, the interaction between the drug and the cyclodextrin is weakened. A phenomenological limit association curve is proposed to define the limiting conditions for association in the presence of an alcohol as a cosolvent. Copyright 1999 Academic Press.

Journal Article↗

Induction of UDP-Glucose:Salicylic Acid Glucosyltransferase Activity in Tobacco Mosaic Virus-Inoculated Tobacco (Nicotiana tabacum) Leaves.

Salicylic acid (SA) is a putative signal that activates plant resistance to pathogens. SA levels increase systemically following the hypersensitive response produced by tobacco mosaic virus (TMV) inoculation of tobacco (Nicotiana tabacum L. cv Xanthi-nc) leaves. The SA increase in the inoculated leaf coincided with the appearance of a [beta]-glucosidase-hydrolyzable SA conjugate identified as [beta]-O-D-glucosylsalicylic acid (GSA). SA and GSA accumulation in the TMV-inoculated leaf paralleled the increase in the activity of a UDP-glucose:salicylic acid 3-O-glucosyltransferase (EC 2.4.1.35) ([beta]-GTase) capable of converting SA to GSA. Healthy tissues had constitutive [beta]-GTase activity of 0.076 milliunits g-1 fresh weight. This activity started to increase 48 h after TMV inoculation, reaching its maximum (6.7-fold induction over the basal levels) 72 h after TMV inoculation. No significant GSA or elevated [beta]-Gtase activity could be detected in the healthy leaf immediately above the TMV-inoculated leaf. The effect of TMV inoculation on the [beta]-GTase and GSA accumulation could be duplicated by infiltrating tobacco leaf discs with SA at the levels naturally produced in TMV-inoculated leaves (2.7-27.0 [mu]g g-1 fresh weight). Pretreatment of leaf discs with the protein synthesis inhibitor cycloheximide inhibited the induction of [beta]-GTase by SA and prevented the formation of GSA. Of 12 analogs of SA tested, only 2,6-dihydroxybenzoic acid induced [beta]-GTase activity.

Journal Article↗

2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[H]quinoline-4-carboxylic acid (PSI-697): identification of a clinical candidate from the quinoline salicylic acid series of P-selectin antagonists.

P-selectin-PSGL-1 interaction causes rolling of leukocytes on the endothelial cell surface, which subsequently leads to firm adherence and leukocyte transmigration through the vessel wall into the surrounding tissues. P-selectin is upregulated on the surface of both platelets and endothelium in a variety of atherosclerosis-associated conditions. Consequently, inhibition of this interaction by means of a small molecule P-selectin antagonist is an attractive strategy for the treatment of atherosclerosis. High-throughput screening and subsequent analoging had led to the identification of compound 1 as the lead candidate. Herein, we report the continuation of this work and the discovery of a second-generation series, the tetrahydrobenzoquinoline salicylic acids. These compounds have improved pharmacokinetic properties, and a number of them have shown oral efficacy in mouse and rat models of atherogenesis and vascular injury. The lead 31 (PSI-697), is currently in clinical development for the treatment of atherothrombotic vascular events.

Administration, Oral↗

[Clinical effect of salicylic acid and high dose urea applied according to the standardized New German Formulary].

OBJECTIVE: To determine whether salicylic acid and high dose urea in five different NRF (New German Formulary) formulations have an effect on stratum corneum. METHODS: 20 healthy volunteers had their stratum corneum blacked with silver nitrate and a photographic developer, and a chromameter (a*-value) was used to determine the amount of discoloration produced by the study products and the drug free vehicles after 24 hours semiocclusive application and 24 hours later. The change in fingerpad ridge width produced by the study formulations and drugfree vehicles was determined at the same time, using the Hikoscope Dermatoscope after 30 and 35 minutes' use under an occlusive dressing. The results obtained with the two methods were correlated. RESULTS: All study formulations were effective. There were differences in the time course of the effects on the stratum corneum. The fingerpad ridge width method is not a measure of keratolytic activity because there were no significant correlations between the results obtained with the two methods. Also, 40% urea was keratolytic in the silver nitrate test, but had no effect of fingerpad ridge width. CONCLUSIONS: All NRF study formulations were effective in the stratum corneum. The fingerpad ridge width method is not a measure of keratolytic activity but rather of an other unknown effect of salicylic acid.

Administration, Topical↗

Accumulation of wound-inducible ACC synthase transcript in tomato fruit is inhibited by salicylic acid and polyamines.

Regulation of wound-inducible 1-aminocyclopropane-1-carboxylic acid (ACC) synthase expression was studied in tomato fruit (Lycopersicon esculentum cv. Pik-Red). A 70 base oligonucleotide probe homologous to published ACC synthase cDNA sequences was successfully used to identify and analyze regulation of a wound-inducible transcript. The 1.8 kb ACC synthase transcript increased upon wounding the fruit as well as during fruit ripening. Salicylic acid, an inhibitor of wound-responsive genes in tomato, inhibited the wound-induced accumulation of the ACC synthase transcript. Further, polyamines (putrescine, spermidine and spermine) that have anti-senescence properties and have been shown to inhibit the development of ACC synthase activity, inhibited the accumulation of the wound-inducible ACC synthase transcript. The inhibition by spermine was greater than that caused by putrescine or spermidine. The transcript level of a wound-repressible glycine-rich protein gene and that of the constitutively expressed rRNA were not affected as markedly by either salicylic acid or polyamines. These data suggest that salicylic acid and polyamines may specifically regulate ethylene biosynthesis at the level of ACC synthase transcript accumulation.

Base Sequence↗

Synthesis of [11C]salicylic acid and related compounds and their biodistribution in mice.

For in vivo measurement of the hydroxyl radical (.OH), we synthesized [11C]salicylic acid, [11C]O-acetylsalicylic acid and [11C]2-methoxybenzoic acid by carboxylation of 2-bromomagnesiumanisol using [11C]CO2. The radiochemical yield of [11C]salicylic acid, [11C]O-acetylsalicylic acid and [11C]2-methoxybenzoic acid calculated from trapped [11C]CO2 in a liquid argon cooled stainless tube was 7.3 +/- 1.6, 5.2 and 10.2 +/- 1.7% (decay corrected), respectively. The uptake of 11C tracers by mouse brain was 0.46, 0.32, and 0.46% dose/g tissue, respectively, at 10 min post injection and presented washout patterns thereafter.

Acetylation↗

[Level of cytokines, abscisic and salicylic acids in the leafs of Phlox under the effect of invasion by conidia of phytopathogens].

We studied the effects of the invasion of Phlox paniculata L. and Ph. setacea L. by causative agents of the phlox powdery mildew (compatible combination) and lupine powdery mildew (incompatible combination) on the level of endogenous cytokinins and abscisic and salicylic acids. In all experimental variants, the level of zeatin-riboside and abscisic and salicylic acids in the leaves of invaded plants increased within 48 h. The highest level of phytohormones and salicylic acid was recorded in the absolutely resistant species Ph. setacea.

Abscisic Acid↗

[Effect of salicylic acid on the blanching effect of flumethasone pivalate (author's transl)].

Test results are reported of the effect of salicylic acid on the vasoconstrictive effect of flumethasone pivalate. In specific, the depigmentation of the skin (identical with increase in lightness of the skin) following topical application of flumethasone pivalate was investigated with the aid of an improved spectrophotometric method. Using numeric lightness evaluation it was possible to demonstrate that salicylic acid increases the vasoconstriction.

Adult↗