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PubMed1984

Gastric and intestinal absorption of captopril in acutely and chronically treated rats: comparison with salicylic acid.

The gastric and intestinal absorption of captopril, an orally active angiotensin-converting enzyme inhibitor was determined using rat in situ gastric pouch and intestinal loop techniques and compared with the absorption of another acidic drug, salicylic acid, whose absorption has been well established from both gastric and intestinal sites. Captopril absorption was determined at two initial intraluminal concentrations in acute (untreated) rats and in rats that had been chronically treated with captopril. Salicylic acid absorption was determined at one concentration in acute rats. During the 40-min experimental period, captopril absorption at the 4.6 mM dose from the gastric pouch was 17.0 +/- 1.8% and 17.9 +/- 5.4% in acute and chronically treated rats, respectively, and 33.6 +/- 9.2% and 23.7 +/- 7.6%, respectively, from the intestinal loop. At the 11.5 mM dose the captopril absorption in 40 min was 13.7 +/- 2.7% and 17.3 +/- 4.2% from the gastric pouch of acutely and chronically treated rats, respectively, and 17.8 +/- 4.2% and 22.9 +/- 3.3%, respectively, from the intestinal loop. As similar fractions of the different administered doses were absorbed from the respective gastric and intestinal sites in both acutely and chronically treated rats, the absorption process of captopril appears to be principally by passive diffusion and unaffected by chronic administration of captopril. In comparison, salicylic acid was absorbed more rapidly and to a greater extent from both the gastric and intestinal preparations. The percent of salicylic acid absorbed into the plasma at the 11.5 mM dose was 44.8 +/- 4.4% and 65.3 +/- 5.3% from the gastric and intestinal preparations, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1978

The determination of salicylic acid and benzoic acid in pharmaceutical formulations by spectrofluorimetry.

Methods of extraction from pharmaceutical formulations and subsequent determination of benzoic acid and salicylic acid by spectrofluorimetry are described. The recovery of benzoic acid, in the presence of salicylic acid, was 99.3%, with a coefficient of variation of 1.04%, while the recovery of salicylic acid, in the presence of benzoic acid, was 97.7%, with a coefficient of variation of 0-68%.

Benzoates↗
PubMed1988

Further studies on the hydrolysis of salicyluric acid in intestinal microorganisms and prolonged blood concentration of salicylic acid following rectal administration of salicyluric acid in rabbits.

The blood concentrations of salicyluric acid and salicylic acid following intracecal and rectal administration of salicyluric acid were determined in rabbits. Immediate and very extensive salicylic acid formation in the cecum was found following intracecal administration. After rectal administration, a small amount of salicyluric acid was absorbed in intact form. The rest was rapidly hydrolyzed to salicylic acid, which was subsequently absorbed. The blood concentration of salicylic acid was maintained at 1.3-1.8 micrograms/ml from 2 to 12 h. Three doses of salicyluric acid were administered rectally. The peak level of salicyluric acid increased with dose. However, salicylic acid concentration in the blood following administration of salicyluric acid at 10.0 mg/kg (salicylic acid equivalent) was not double that observed following administration of salicyluric acid at 5.0 mg/kg (salicylic acid equivalent). It appears that a larger amount of salicyluric acid in the rectal lumen may have saturated the glycine deconjugation system.

Administration, Rectal↗
PubMed2026

Mechanisms of Transcriptional Regulation by Salicylic Acid Receptors.

Salicylic acid (SA) is a key phytohormone that activates plant defense responses 1-3. In Arabidopsis, NPR1 (also known as NIM1) and NPR3/NPR4 have been identified as dual SA receptors responsible for perceiving SA 4-6. However, the mechanisms of how SA binding to the NPR proteins leads to induction of defense gene expression remain unclear. Here, we elucidate how SA triggers transcriptional activation via NPR1 and relieves transcriptional repression mediated by NPR3/NPR4. We identified Mediator Complex Subunit 15A (MED15A) as a bridge between NPR1 and the Mediator complex governing transcription. SA induces direct interaction of NPR1 with MED15A. Structural and functional analysis showed that the binding of NPR1 to MED15A is essential for NPR1-mediated transcriptional activation. Meanwhile, SA relieves transcriptional repression mediated by NPR3/NPR4. NIM1-interacting 1 (NIMIN1) interacts with NPR3/NPR4 and the Topless (TPL) co-repressor, connecting them to Polycomb Repressive Complex 2 (PRC2) to mediate H3K27 trimethylation of SA-responsive genes. SA inhibits the interactions between NPR3/NPR4 and NIMIN1, reduces H3K27 trimethylation levels and increases histone acetylation of the target genes to release NPR3/NPR4-mediated repression. Our study offers a comprehensive view of SA-mediated defense gene activation. These findings lay a foundation for designing more effective SA analogs as agrochemicals and for engineering crop resistance by manipulating SA perception and signaling.

Journal Article↗
PubMed1988

Hydrolysis of salicyluric acid in intestinal microorganisms and prolonged blood concentration of salicylic acid following rectal administration of salicyluric acid in rats.

The blood concentrations of salicyluric acid and salicylic acid following oral, intravenous, intracecal and rectal administration of salicyluric acid were determined in rats. After oral administration of salicyluric acid, salicyluric acid was rapidly absorbed. Salicylic acid was detected at low concentration. Following intravenous administration of salicyluric acid, salicyluric acid was detected in the blood and was rapidly eliminated. A trace amount of salicylic acid was detected, suggesting that systemic deconjugation of glycine was involved. Furthermore, in vitro incubation of salicyluric acid with contents of the gut showed that the major source of the hydrolysis was the hind gut. Immediate and very extensive salicylic acid formation in the cecum was found following intracecal administration of salicyluric acid. The blood concentration of salicylic acid was maintained at 2.6-4.0 micrograms/ml from 4 to 12 h following rectal administration of salicyluric acid (10 mg/kg: salicylic acid equivalent). Species difference in the metabolic fate of salicyluric acid in rats and rabbits reported previously is discussed.

Administration, Oral↗
PubMed1978

Effect of repeated skin application on percutaneous absorption of salicylic acid.

Various concentrations of salicylic acid in hydrophilic ointment were applied repeatedly at daily or weekly intervals to rats in vivo. Salicylic acid absorption through treated skin was monitored by determining the penetration fluxes of salicylic acid through skin excised at various times. A gradual decrease in the salicylic acid penetration flux was observed following weekly applications of either 5 or 10% salicylic acid in hydrophilic ointment. The penetration flux of 1% salicylic acid remained constant. In the daily applications of 5 and 10% salicylic acid, the penetration flux increased after approximately 2 days of treatment and declined thereafter. The penetration flux of salicylic acid from the 1% salicylic acid increased slightly after 3--4 days of treatment.

Administration, Topical↗
PubMed1981

Characterization of the inhibition of k absorption in oat roots by salicylic Acid.

The phenolic compounds salicylic acid (o-hydroxybenzoic acid) and ferulic acid (4-hydroxy-3-methoxycinnamic acid) inhibited K(+) ((86)Rb(+)) absorption in excised oat (Avena sativa L. cv. Goodfield) root tissue. Salicylic acid was the most inhibitory. The degree of inhibition was both concentration- and pH-dependent. With decreasing pH, the inhibitory effect of the phenolic increased. During the early stages of incubation, the time required to inhibit K(+) absorption was also pH- and concentration-dependent. At pH 4.0, 5x10(-4) molar salicylic acid inhibited K(+) absorption about 60% within 1 minute; whereas, at pH 6.5, this concentration affected absorption only after 10 to 15 minutes. However, at 5 x 10(-3) molar and pH 6.5, salicylic acid was inhibitory within 1 minute. The capacity of the tissue to recover following a 1-hour treatment in 5 x 10(-4) molar salicylic acid ranged from no recovery at pH 4.5 to complete recovery at pH 7.5. The absorption of salicylic acid was pH-dependent, also. As pH decreased, more of the phenolic compound was absorbed by the tissue. The increased absorption of the compound at low pH most likely contributed to apparent tissue damage at pH 4.5 and might have accounted for the lack of recovery of K(+) absorption as pH decreased.Under the proper conditions of pH and concentration, phenolic acids such as salicylic acid could significantly affect mineral absorption by plants in the field.

Journal Article↗
PubMed2006

Arabidopsis leaf necrosis caused by simulated acid rain is related to the salicylic acid signaling pathway.

Arabidopsis leaves treated with simulated acid rain (SiAR) showed phenotypes similar to necrotic lesions caused by biotic stresses like Pseudomonad infiltration. Exposure of Arabidopsis to SiAR resulted in the up-regulation of genes known to be induced by the salicylic acid (SA)-mediated pathogen resistance response. The expression of enhanced disease susceptibility (EDS), nonexpressor of PR (NPR) and pathogen-related 1 (PR1), all of which are involved in the salicylic acid signaling pathway, were increased after SiAR exposure. However, vegetative storage protein (VSP), a member of the jasmonic acid pathway did not show a significant change in transcript level. SiAR treatment of transgenic plants expressing salicylate hydroxylase (Nah-G), which prevents the accumulation of salicylic acid, underwent more extensive necrosis than wild-type plants, indicating that the signaling pathway activated by SiAR may overlap with the SA-dependent, systemic acquired resistance pathway. Both Col-0 and Nah-G plants showed sensitivity to SiAR and sulfuric SiAR (S-SiAR) by developing necrotic lesions. Neither Col-0 plants nor Nah-G plants showed sensitivity to nitric SiAR (N-SiAR). These results suggest that SiAR activates at least the salicylic acid pathway and activation of this pathway is sensitive to sulfuric acid.

Acid Rain↗
PubMed2006

The role of salicylic acid and jasmonic acid in pathogen defence.

Phytohormones are not only instrumental in regulating developmental processes in plants but also play important roles for the plant's responses to biotic and abiotic stresses. In particular, abscisic acid, ethylene, jasmonic acid, and salicylic acid have been shown to possess crucial functions in mediating or orchestrating stress responses in plants. Here, we review the role of salicylic acid and jasmonic acid in pathogen defence responses with special emphasis on their function in the solanaceous plant potato.

Arabidopsis↗