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Repellent and antifeedant activity of salicylic acid and related compounds against the biting midge, Culicoides impunctatus (Diptera: Ceratopogonidae).

An artificial membrane, blood-feeding method was used to assess the repellent and antifeedant effects of derivatives of salicylic acid on the biting midge Culicoides impunctatus Goetghebeur. Trans-2-hydroxycyclohexanecarboxylic acid, 6-methylsalicylic acid, 2,6-dihydroxy-4-methylbenzoic acid, and salicyluric acid caused highly significant inhibition of feeding, with salicyluric acid performing significantly greater than the other compounds. Investigating the effects of alkyl substitution of salicylic acid, o-thymotic and o-cresotic acids were also effective. A pilot clinical trial using salicyluric acid indicated that it provided a protective effect and it was hypothesized that this may have resulted primarily from contact, because no significant repellent effects were shown for this compound in a microscope slide test, designed to demonstrate repellency with volatile compounds.

Animals↗

Salicylic acid inhibits jasmonic acid-induced resistance of Arabidopsis thaliana to Spodoptera exigua.

The role of salicylic acid (SA) in plant responses to pathogens has been well documented, but its direct and indirect effects on plant responses to insects are not so well understood. We examined the effects of SA, alone and in combination with jasmonic acid (JA), on the performance of the generalist herbivore, Spodoptera exigua, in wild-type and mutant Arabidopsis thaliana genotypes that varied genetically in their ability to mount SA- and JA-mediated defence responses. In one experiment, growth of S. exigua larvae was highest on the Wassilewskija wild-type, intermediate on the Columbia wild-type and the JA-deficient fad mutant, and lowest on the nim1-1 and jar1-mutants, which are defective in the SA and JA pathways, respectively. Activity of guaiacol peroxidase, polyphenoloxidase, n-acetylglucosaminidase, and trypsin inhibitor varied by genotype but did not correlate with insect performance. SA treatment increased growth of S. exigua larvae by approximately 35% over all genotypes, but had no discernable effect on activities of the four defence proteins. In a second experiment, growth of S. exigua was highest across treatments on the cep1 mutant, a constitutive expressor of high SA levels and systemic acquired resistance, and lowest on the fad mutant, which is JA-deficient. JA treatment generally increased activity of all four defence proteins, increased total glucosinolate levels and reduced insect growth by approximately 25% over all genotypes. SA generally inhibited expression of JA-induced resistance to S. exigua when both hormones were applied simultaneously. Across genotypes and treatments, larval mass was negatively correlated with the activity of trypsin inhibitor and polyphenoloxidase and with total glucosinolate levels, and insect damage was negatively correlated with the activity of polyphenoloxidase. SA had little effect on the induction of defence protein activity by JA. However, SA attenuated the induction of glucosinolates by JA and therefore may explain better the interactive effects of SA and JA on insect performance. This study illustrates that direct and indirect cross-effects of SA on resistance to S. exigua can occur in A. thaliana. Effects of SA may be mediated through effects on plant defence chemistry or other aspects of the suitability of foliage for insect feeding and growth.

Acetylglucosaminidase↗

Application of salicylic acid dosimetry to evaluate hydrodynamic cavitation as an advanced oxidation process.

The generation of OH* radicals inside hydrodynamic cavitation bubbles was monitored using a salicylic acid dosimeter. The reaction of this scavenger with OH* produces 2,5-dihydroxybenzoic acid (2,5-DHB) and, to a lesser degree, 2,3-DHB. The former, is a specific reaction product that can be determined with a very high sensitivity using HPLC-IF. This method has been applied to study the influence of the flow-rate and the solution pH for a given cavitation chamber geometry. The salicylic dosimetry has proven especially suitable for the characteristic time scales of hydrodynamic cavitation (higher than those of ultrasonic cavitation), which usually gives rise to recombination of radicals before they can reach the liquid-phase. Working at low pH the hydrophobic salicylic acid migrates to the gas-liquid interface and reacts with the OH* radicals, increasing the trapping efficiency of the dosimeter. Hydrodynamic cavitation works as a very low frequency sonochemical reactor, and therefore its potential as an Advanced Oxidation Process might be limited to reactions at the gas-liquid interface and inner bubble (i.e. with volatiles and/or hydrophobic substances).

Journal Article↗

Comparison of the effect of oral sulphasalazine, sulphapyridine and 5-amino-salicylic acid on the in vivo antibody response to oral and systemic antigen.

1. Mice, whose drinking water contained sulphasalazine, sulphapyridine or 5-amino-salicylic acid, received an antigenic challenge by cholera toxin administered either orally or systemically. 2. Sulphasalazine treated mice made less specific antibody of IgA class provided the antigen also was administered orally (P = 0.009 for days 7-28). When the antigen was administered systemically, there was a vigorous anti-cholera toxin antibody response of IgG class, and a lesser IgM but only a weak IgA response. The effect of sulphasalazine in this case was confined to the IgG response, which was significantly suppressed on day 28 (P = 0.008). 3. Sulphapyridine and 5-amino salicylic acid had no significant effect on the anti-cholera toxin (CT) responses of all three classes. 4. It therefore appears that in this model, only sulphasalazine is capable of influencing the humoral immune system, the antibody class affected depending on the route of entry of antigen. This may have implications for conditions such as rheumatoid arthritis and chronic inflammatory bowel disease, for which sulphasalazine has been found useful.

Administration, Oral↗

Differential effects of elevated ozone on two hybrid aspen genotypes predisposed to chronic ozone fumigation. Role of ethylene and salicylic acid.

The role of ethylene (ET) signaling in the responses of two hybrid aspen (Populus tremula L. x P. tremuloides Michx.) clones to chronic ozone (O(3); 75 nL L(-1)) was investigated. The hormonal responses differed between the clones; the O(3)-sensitive clone 51 had higher ET evolution than the tolerant clone 200 during the exposure, whereas the free salicylic acid concentration in clone 200 was higher than in clone 51. The cellular redox status, measured as glutathione redox balance, did not differ between the clones suggesting that the O(3) lesions were not a result of deficient antioxidative capacity. The buildup of salicylic acid during chronic O(3) exposure might have prevented the up-regulation of ET biosynthesis in clone 200. Blocking of ET perception with 1-methylcyclopropene protected both clones from the decrease in net photosynthesis during chronic exposure to O(3). After a pretreatment with low O(3) for 9 d, an acute 1.5-fold O(3) elevation caused necrosis in the O(3)-sensitive clone 51, which increased substantially when ET perception was blocked. The results suggest that in hybrid aspen, ET signaling had a dual role depending on the severity of the stress. ET accelerated leaf senescence under low O(3), but under acute O(3) elevation, ET signaling seemed to be required for protection from necrotic cell death.

Adaptation, Physiological↗

Studies on the effect of salicylic acid on normal skin.

This investigation was prompted by our ignorance of the way in which salicyclic acid aids desquamation. Salicyclic acid in aqueous cream or white soft paraffin and in concentrations of 2-12% was applied to normal skin of twenty-three subjects while the vehicle alone was applied to the contralateral sites. Biopsies and skin surface biopsies were taken from the test and control sites after 1 week. Histological examination showed that there was less horny layer on the test specimens but that there were no qualitative or quantitative differences in the structure of the viable epidermis. Portions of the biopsies were incubated in the presence of tritiated precursor compounds and subsequent autoradiographic examination showed no difference in the incorporation of thymidine, cytidine or histidine between test and control preparations. Scanning electron microscopy of skin surface biopsies showed some changes in all specimens--presumably due to hydration--but also showed striking differences between test and control sites and were especially marked with higher concentrations of salicylic acid. It is suggested that salicylic acid causes desquamation by dissolution of intercellular cement material.

Autoradiography↗

Pti4 is induced by ethylene and salicylic acid, and its product is phosphorylated by the Pto kinase.

The tomato Pti4 gene encodes a transcription factor that was identified on the basis of its specific interaction with the product of the Pto disease resistance gene in a yeast two-hybrid system. We show here that the Pti4 protein specifically binds the GCC-box cis element, which is present in the promoter region of many pathogenesis-related (PR) genes. Expression of the Pti4 gene in tomato leaves was rapidly induced by ethylene and by infection with Pseudomonas syringae pv tomato, and this induction preceded expression of GCC-box-containing PR genes. Although salicylic acid also induced Pti4 gene expression, it did not induce GCC-box PR genes. Rather, salicylic acid antagonized ethylene-mediated expression of GCC-box PR genes. We demonstrate that the Pti4 protein is specifically phosphorylated by the Pto kinase and that this phosphorylation enhances binding of Pti4 to the GCC box. In addition, induced overexpression of Pto and Pti4 in tomato leaves resulted in a concomitant increase in GCC-box PR genes. Our results support a model in which phosphorylation of the Pti4 protein by the Pto kinase enhances the ability of Pti4 to activate expression of GCC-box PR genes in tomato.

Cycloheximide↗

Suppression by ABA of salicylic acid and lignin accumulation and the expression of multiple genes, in Arabidopsis infected with Pseudomonas syringae pv. tomato.

Abscisic acid (ABA) has been implicated in determining the outcome of interactions between many plants and their pathogens. We had previously shown that increased concentrations of ABA within leaves of Arabidopsis induced susceptibility towards an avirulent strain of Pseudomonas syringae pathovar (pv.) tomato. We now show that ABA induces susceptibility via suppression of the accumulation of components crucial for a resistance response. Lignin and salicylic acid concentrations in leaves were increased during a resistant interaction but reduced when plants were treated with ABA. The reduction in lignin and salicylic acid production was independent of the development of the hypersensitive response (HR), indicating that, in this host-pathogen system, HR is not required for resistance. Genome-wide gene expression analysis using microarrays showed that treatment with ABA suppressed the expression of many defence-related genes, including those important for phenylpropanoid biosynthesis and those encoding resistance-related proteins. Together, these results show that resistance induction in Arabidopsis to an avirulent strain of P. syringae pv. tomato is regulated by ABA.

Abscisic Acid↗

Disposition of salicylic acid in malnourished Ethiopian children after single oral dose.

The disposition of salicylic acid and salicyluric acid was studied in 57 Ethiopian children of varying nutritional status after oral administration of sodium salicylate in single doses of either 12.5 or 25 mg/kg. There was no apparent influence of nutritional status on oral salicylate disposition when related to total plasma concentrations. Unbound concentrations were predicted from total plasma concentrations on the basis of a single time point determination of protein binding in each individual, according to a Scatchard model. Areas under the unbound plasma concentration-time curve were larger and the fractional excretion of salicyluric acid was lower in children with kwashiorkor compared with control individuals. This was interpreted as lower hepatocellular metabolic activity in patients with kwashiorkor. Children with marasmus retained an unimpaired capacity for salicylate metabolism. The influence of saturable distribution and elimination are discussed.

Administration, Oral↗

Dermo-epidermal stimulation elicited by a beta-lipohydroxyacid: a comparison with salicylic acid and all-trans-retinoic acid.

Although ageing has been thought to be irreversible, studies made during the last decade have shown that a few topical compounds may limit or improve the age-related skin damages. The efficacy of tretinoin (all-trans-retinoic acid) in treating photoageing is well established. Identifying other compounds with similar effect and improved tolerance would be greatly valued. In this double-blind study, a new beta-lipohydroxyacid compound was evaluated. To address a comparison between products, 6 volunteers completed a 4-week study using twice daily 0.025% tretinoin, 5% salicylic acid, 1.5% beta-lipohydroxyacid or vehicle. Immunohistochemistry and computerized image analysis were performed on skin sections from biopsies taken after treatment. We searched for changes in epidermal renewal (Ki-67 labeling), modifications in cytokeratin (56-65 kD) and filaggrin patterns, and in tumor necrosis factor alpha (TNF-alpha), Ulex europaeus and factor XIIIa expressively. The vehicle- and salicylic-acid-treated areas had an aspect similar to untreated control sites. Both beta-lipohydroxyacid and tretinoin induced enhanced epidermal proliferation and thickness with activation of factor XIIIa+dendrocytes. The effects were more pronounced at the tretinoin-treated site. We speculate that TNF-alpha might mediate some of the dermal effects. The beta-lipohydroxyacid mimics some of the stimulatory effects of tretinoin on the epidermis and dermis. This new compound should be listed among topical products boosting the skin tissues affected by ageing.

Administration, Topical↗

The salicylate trapping method: is oxidation of salicylic acid solution oxygen and time dependent and metal catalysed?

For a microdialytic trapping method we systematically investigated changes in concentrations of 2,5-dihydroxy-benzoic acid (2,5-DHBA) and 2,3-dihydroxy-benzoic acid (2,3-DHBA) in freshly prepared solutions of salicylic acid (SA). The solvent was 0.9% saline exposed to different atmospheric concentrations of oxygen (0, 21, and 100%). The solutions were treated by freezing-thawing and an ultrasonic bath in presence and absence of aluminium foil. Without aluminium the concentrations of 2,5-DHBA and 2,3-DHBA kept constant over an observed period of 160 min on different levels from below 20 ng/ml to about 100 ng/ml. In presence of aluminium the concentrations increased to maximum 307 ng/ml after 160 min. Ultrasonic irradiation amplified this effect to maximum 341 ng/ml. HPLC/ECD processing and quantitative analysis of dihydroxy-benzoic acids (DHBAs) in microdialysis may be artificially influenced by varying oxygen environment and metal catalysis.

Aluminum↗

Does salicylic acid increase the percutaneous absorption of diflucortolone-21-valerate?

The percutaneous absorption of diflucortolone-21-valerate (DFV) and its effect on the pituitary adrenal system were investigated during large skin area treatment (20 g ointment twice a day for 8 days) of two groups of healthy volunteers with Nerisona and Nerisalic ointment, respectively. Plasma levels of diflucortolone, cortisol and dehydroepiandrosterone (DHEA) were measured in both groups whereas plasma levels of salicylic acid were measured additionally in volunteers treated with Nerisalic. No differences, neither in percutaneous absorption of DFV nor in effects on cortisol and DHEA were found between the two treatment groups. There was a slight reduction in cortisol levels under both treatments, but the circadian rhythm was not disturbed. Mean salicylic acid plasma levels under high-dose topical Nerisalic treatment were about 50-fold below levels where toxicity may be expected.

Adult↗

Downy mildew (Peronospora parasitica) resistance genes in Arabidopsis vary in functional requirements for NDR1, EDS1, NPR1 and salicylic acid accumulation.

To better understand the genetic requirements for R gene-dependent defense activation in Arabidopsis, we tested the effect of several defense response mutants on resistance specified by eight RPP genes (for resistance to Peronospora parasitica) expressed in the Col-0 background. In most cases, resistance was not suppressed by a mutation in the SAR regulatory gene NPR1 or by expression of the NahG transgene. Thus, salicylic acid accumulation and NPR1 function are not necessary for resistance mediated by these RPP genes. In addition, resistance conferred by two of these genes, RPP7 and RPP8, was not significantly suppressed by mutations in either EDS1 or NDR1. RPP7 resistance was also not compromised by mutations in EIN2, JAR1 or COI1 which affect ethylene or jasmonic acid signaling. Double mutants were therefore tested. RPP7 and RPP8 were weakly suppressed in an eds1-2/ndr1-1 background, suggesting that these RPP genes operate additively through EDS1, NDR1 and as-yet-undefined signaling components. RPP7 was not compromised in coi1/npr1 or coi1/NahG backgrounds. These observations suggest that RPP7 initiates resistance through a novel signaling pathway that functions independently of salicylic acid accumulation or jasmonic acid response components.

Arabidopsis↗

ocs element promoter sequences are activated by auxin and salicylic acid in Arabidopsis.

ocs elements are a group of promoter elements that have been exploited by two distinct groups of plant pathogens, Agrobacterium and certain viruses, to express genes in plants. We examined the activity of single and multiple ocs elements linked to a minimal plant promoter and the uidA reporter gene in transgenic Arabidopsis. beta-Glucuronidase activity was detected only in root tips and in callus tissue after auxin treatment. A more sensitive assay revealed that auxin treatment also increased ocs element activity in aerial parts of the plant, although the absolute levels of ocs element activity were greater in roots. The response of ocs elements to exogenous auxin began within 1 h. Salicylic acid, a disease-resistance signal in plants, also increased ocs element activity in both roots and aerial parts of the plant. The question of whether the induction in ocs element activity is mediated through auxin and/or salicylic acid signal transduction pathways or is part of a more general stress response is discussed.

Arabidopsis↗

Interactions of aspirin and salicylic acid with prednisolone for inhibition of lymphocyte proliferation.

The anti-inflammatory properties of salicylates and prednisolone were investigated using inhibition of in vitro phytohemagglutinin-stimulated lymphocyte proliferation in human whole blood from healthy male and female subjects. Steroids and salicylates are used in conjunction for the treatment of inflammatory disorders such as rheumatoid arthritis and inhibit the proinflammatory transcription factor, NFKB, by different mechanisms. Data generated using various combinations of these drugs were analyzed using isobolograms and the universal surface response approach based on the Loewe additivity principle. The interaction between aspirin and prednisolone was mildly antagonistic while that between salicylic acid and prednisolone was modestly synergistic at therapeutic concentrations. Further, aspirin was slightly more potent in males, but the nature of the steroid-salicylate interaction was similar across genders. This study helps rationalize part of the beneficial effects of steroids and salicylates in treatment of inflammatory disorders.

Adult↗

Comparative effects of retinoic acid, glycolic acid and a lipophilic derivative of salicylic acid on photodamaged epidermis.

BACKGROUND: Studies comparing purported antiaging compounds are rare. OBJECTIVE: To compare in a randomized, placebo-controlled double-blind study 10% glycolic acid (GA), 2% 2-hydroxy-5-octanoyl benzoic acid (beta-lipohydroxy acid, LSA) and 0.05% all-trans-retinoic acid (RA). METHODS: Women volunteers treated one forearm twice daily with one of the active products and the other one with the vehicle. Comparative evaluations of efficacy were made using histochemistry and quantitative immunohistochemistry. RESULTS: Improvement in the various epidermal compartments was the most prominent finding at the RA-treated site. The LSA-treated site also exhibited similar positive changes, although to a lesser degree. GA showed no significant effect. CONCLUSION: In the presently tested concentrations and formulations, RA had a beneficial impact upon the aging epidermis. LSA mimicked RA but with somewhat lesser efficacy. By contrast, GA appeared almost inactive.

Double-Blind Method↗