salicylates and 4-hydroxybenzoic-acid

An overview is presented of a selected number of mono-aromatic derivatives and their short-term effects on hepatic fatty acid biosynthesis. The compounds discussed in this paper are ortho-hydroxybenzoate (salicylate), meta-hydroxybenzoate, para-hydroxybenzoate, benzoate, para-t-butylbenzoate, para-aminosalicylate, clofibrate, halofenate, alpha-cyano-4-hydroxycinnamate and benfluorex. All of these drugs inhibit fatty acid biosynthesis by isolated rat liver cells, albeit with different effectiveness. In contrast, the compounds have differential effects on fatty acid esterification and oxidation by isolated hepatocytes. An attempt is made to describe in molecular terms the underlying mechanisms of the acute inhibitory effects of the mono-aromatic derivatives on hepatic lipogenesis. It is proposed that all of the drugs exert an inhibitory action at the level of acetyl-CoA carboxylase, the enzyme generally considered to catalyse the rate-limiting step in hepatic fatty acid synthesis. This inhibitory effect may be either direct, i.e. by an alteration of the enzyme's structure as a result of interaction between drug and enzyme, or indirect, i.e. through a drug-induced change in the cellular levels of allosteric effectors of acetyl-CoA carboxylase.

Topics: Acetyl-CoA Carboxylase; Aminosalicylic Acid; Animals; Benzene Derivatives; Benzoates; Benzoic Acid; Carbohydrate Metabolism; Clofibrate; Coumaric Acids; Fatty Acids; Fenfluramine; Halofenate; Hydroxybenzoates; Lipids; Liver; Models, Biological; Oxidation-Reduction; Parabens; Rats; Salicylates; Salicylic Acid

Mechanisms by which dissolved organic matter (DOM) mediates the photochemical reduction of Hg(II) in aquatic ecosystems are not fully understood, owing to the heterogeneous nature and complex structural properties of DOM. In this work, naturally occurring aromatic compounds including salicylic, 4-hydrobenzoic, anthranilic, 4-aminobenzoic, and phthalic acid were systematically studied as surrogates for DOM in order to gain an improved mechanistic understanding of these compounds in the photoreduction of Hg(II) in water. We show that the photoreduction rates of Hg(II) are influenced not only by the substituent functional groups such as -OH, -NH(2) and -COOH on the benzene ring, but also the positioning of these functional groups on the ring structure. The Hg(II) photoreduction rate decreases in the order anthranilic acid>salicylic acid>phthalic acid according to the presence of the -NH(2), -OH, -COOH functional groups on benzoic acid. The substitution position of the functional groups affects reduction rates in the order anthranilic acid>4-aminobenzoic acid and salicylic acid>4-hydroxybenzoic acid. Reduction rates correlate strongly with ultraviolet (UV) absorption of these compounds and their concentrations, suggesting that the formation of organic free radicals during photolysis of these compounds is responsible for Hg(II) photoreduction. These results provide insight into the role of low-molecular-weight organic compounds and possibly DOM in Hg photoredox transformation and may thus have important implications for understanding Hg geochemical cycling in the environment.

Topics: 4-Aminobenzoic Acid; Mercury Compounds; Molecular Weight; ortho-Aminobenzoates; Oxidation-Reduction; Parabens; Photolysis; Phthalic Acids; Salicylates; Water; Water Pollutants, Chemical

Salicylic acid methyltransferases (SAMTs) synthesize methyl salicylate (MeSA) using salicylate as the substrate. MeSA synthesized in plants may function as an airborne signal to activate the expression of defense-related genes and could also be a critical mobile signaling molecule that travels from the site of plant infection to establish systemic immunity in the induction of disease resistance. Here the results of QM/MM free energy simulations for the methyl transfer process in Clarkia breweri SAMT (CbSAMT) are reported to determine the origin of the substrate specificity of SAMTs. The free energy barrier for the methyl transfer from S-adenosyl-L-methionine (AdoMet) to 4-hydroxybenzoate in CbSAMT is found to be about 5 kcal/mol higher than that from AdoMet to salicylate, consistent with the experimental observations. It is suggested that the relatively high efficiency for the methylation of salicylate compared to 4-hydroxybenzoate is due, at least in part, to the reason that a part of the stabilization of the transition state (TS) configuration is already reflected in the reactant complex, presumably, through the binding. The results seem to indicate that the creation of the substrate complex (e.g., through mutagenesis and substrate modifications) with its structure closely resembling TS might be fruitful for improving the catalytic efficiency for some enzymes. The results show that the computer simulations may provide important insights into the origin of the substrate specificity for the SABATH family and could be used to help experimental efforts in generating engineered enzymes with altered substrate specificity.

Topics: Binding Sites; Catalysis; Clarkia; Computer Simulation; Methylation; Methyltransferases; Models, Molecular; Parabens; Plant Immunity; Plant Proteins; Protein Binding; Protein Engineering; S-Adenosylmethionine; Salicylates; Salicylic Acid; Substrate Specificity; Thermodynamics

The detection of reactive oxygen species (ROS) after traumatic brain injury (TBI) is based on indirect methods due to the high reactivity and short half-life of ROS in biological tissue. The commonly used salicylate trapping method has several disadvantages making it unsuitable for human use. We have evaluated 4-hydroxybenzoic acid (4-HBA) together with microdialysis (MD) in the rat as an alternative method. 4-HBA forms one stable adduct, 3,4-dihydroxybenzoic acid (3,4-DHBA), when reacting with ROS and has not previously been used together with MD after TBI. Twenty-seven rats were used for the assessment of 3,4-DHBA production as an indicator of ROS formation in a controlled contusion injury model using intracerebral MD with 3 mM 4-HBA in the perfusate. For comparison, salicylate trapping was used in eight rats. TBI caused a 250% increase of 3,4-DHBA that peaked at 30 min after injury in severely injured rats and remained significantly elevated as compared to baseline for 90 min after trauma. The mild injury level caused a 100% increase in 3,4-DHBA formation at 30 min after the injury. When the MD probe was placed in the perimeter of the injury site, no significant increase in ROS formation occurred. Salicylate trapping showed a similar increase in adduct formation after severe injury. In addition, high cortical concentrations of 4-HBA and salicylate were found. It is concluded that microdialysis with 4-HBA as a trapping agent appears to be a useful method for ROS detection in the rat with a potential clinical utility.

Topics: Animals; Blood Pressure; Body Temperature; Brain; Brain Injuries; Chromatography, High Pressure Liquid; Functional Laterality; Hydroxybenzoates; Male; Microdialysis; Parabens; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Salicylates; Spin Trapping

Cucumber (Cucumis sativa) leaves infiltrated with Pseudomonas syringae pv. syringae cells produced a mobile signal for systemic acquired resistance between 3 and 6 h after inoculation. The production of a mobile signal by inoculated leaves was followed by a transient increase in phenylalanine ammonia-lyase (PAL) activity in the petioles of inoculated leaves and in stems above inoculated leaves; with peaks in activity at 9 and 12 h, respectively, after inoculation. In contrast, PAL activity in inoculated leaves continued to rise slowly for at least 18 h. No increases in PAL activity were detected in healthy leaves of inoculated plants. Two benzoic acid derivatives, salicylic acid (SA) and 4-hydroxybenzoic acid (4HBA), began to accumulate in phloem fluids at about the time PAL activity began to increase, reaching maximum concentrations 15 h after inoculation. The accumulation of SA and 4HBA in phloem fluids was unaffected by the removal of all leaves 6 h after inoculation, and seedlings excised from roots prior to inoculation still accumulated high levels of SA and 4HBA. These results suggest that SA and 4HBA are synthesized de novo in stems and petioles in response to a mobile signal from the inoculated leaf.

Topics: Cucumis sativus; Immunity, Innate; Parabens; Phenylalanine Ammonia-Lyase; Plant Diseases; Plant Leaves; Plant Stems; Pseudomonas; Salicylates; Salicylic Acid; Signal Transduction

An improved chemometric approach is proposed for assessing chromatographic peak purity by means of artificial neural networks. A non-linear transformation function with a back-propagation algorithm was used to describe and predict the chromatographic data. The Mann-Whitney U-test was used for the concluding the purity of the chromatographic peak. Simulation data and practical analytical data for both pure and mixture samples were analysed with satisfactory results. A prior knowledge of the impurity and the related compound is unnecessary when a slight difference between their chromatogram and spectrum exists. The performance on simulated data sets by this approach was compared with the results from principal component analysis.

Topics: Algorithms; Caffeic Acids; Chromatography; Hydrogen-Ion Concentration; Hydroxybenzoates; Neural Networks, Computer; Parabens; Salicylates; Salicylic Acid

Rhodococcus erythropolis strain S1 uses the gentisate pathway to metabolize salicylate and m-hydroxybenzoate and the protocatechuate pathway to degrade p-hydroxybenzoate. m-Hydroxybenzoate 6-hydroxylase was induced by growth on m-hydroxybenzoate or gentisate, and salicylate 5-hydroxylase only by growth on salicylate. p-Hydroxybenzoate 3-hydroxylase could be induced only by growth on p-hydroxybenzoate. m-Hydroxybenzoate or p-hydroxybenzoate could repress the induction of salicylate 5-hydroxylase. Maleylpyruvate isomerase in the gentisate pathway did not require reduced glutathione.

Topics: cis-trans-Isomerases; Gentisates; Glutathione; Hydroxybenzoates; Isomerases; Kinetics; Mixed Function Oxygenases; Oxygen Consumption; Parabens; Rhodococcus; Salicylates; Salicylic Acid

While setting up an intracerebral microdialysis system to estimate the extent of oxidative stress induced by the neurotoxin, N-methylphenylpyridinium ion (MPP+), we encountered a problem in the use of hydroxybenzoic acids as traps of hydroxyl radicals. Using either 2-hydroxybenzoate (salicylate) or 4-hydroxybenzoate as trapping agents, we observed a nonspecific, that is, nontissue derived, production of hydroxyl radicals as measured by the hydroxylation products, 2,3- and 2,5-dihydroxybenzoate from 2-hydroxybenzoate and 3,4-dihydroxybenzoate from 4-hydroxybenzoate. This production of dihydroxybenzoates was 10 times that expected due to the administration of MPP+, thus making it impossible to interpret our results. Careful investigation of the various components of the microdialysis system indicated that contact of the microdialysate with metal surfaces resulted in dihydroxybenzoic acid formation. These results should serve as a reminder to perform stringent tests of the experimental system prior to experiments with biological tissues to evaluate the contribution of hydroxyl radical production from nonbiological sources. Therefore, along with the possibility of enzymatic production of dihydroxybenzoates, artefactual production by components of the experimental apparatus must be considered before assuming that one is measuring hydroxyl radical production by a biological system.

Topics: 1-Methyl-4-phenylpyridinium; Animals; Ascorbic Acid; Chromatography, High Pressure Liquid; Dialysis; Free Radical Scavengers; Gas Chromatography-Mass Spectrometry; Hydroxybenzoates; Hydroxyl Radical; Hydroxylation; Male; Oxidation-Reduction; Oxidative Stress; Parabens; Rats; Rats, Sprague-Dawley; Salicylates; Salicylic Acid

The release profile of several drugs, (chlorpheniramine maleate, salicylic acid, hydrochlorothiazide, p-hydroxy benzoic acid, sulphafurazole, anhydrous theophylline) and the marker (D&C yellow No. 10) was detailed to determine the effect of physical and chemical properties on release from selected thermosoftening matrices (Gelucire 50/02 and 50/13). At a concentration of drug or marker of 2.5% w/w, hydrochlorothiazide showed the slowest release from G50/02, due to its low aqueous solubility, while theophylline showed the highest release owing to its low mol. wt and moderate aqueous solubility. Release reflected two of the selection criteria, aqueous solubility and mol. wt, set forth for the drug/markers used in the study. The hydrophobic matrix, G50/02, offered no enhancement in drug release and functioned in a manner commensurate with other hydrophobic matrices. No hydrogen bonding was noted between any of the drugs or markers and the matrix. As drug or marker concentration increased from 2.5 to 15% w/w, potential hydrogen bonding was noted between p-hydroxy benzoic acid and the matrix. Theophylline no longer had the highest release being replaced by chlorpheniramine maleate and D&C yellow No. 10. With Gelucire excipient G50/13, chlorpheniramine maleate showed the highest release; it dissolved within the matrix at experimental temperature and lowered the matrix melting point. The matrix swelled upon exposure to the dissolution medium and it was from this swollen layer that release occurred. Sulphafurazole, hydrochlorothiazide, salicylic acid and p-hydroxy benzoic acid exerted a similar effect to chlorpheniramine maleate on the matrix. No hydrogen bonding was observed between the drugs and matrix.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Calorimetry, Differential Scanning; Chlorpheniramine; Diffusion; Drug Delivery Systems; Excipients; Fats; Oils; Parabens; Salicylates; Salicylic Acid; Temperature; Theophylline

Eight actinomycetes of the genera Amycolatopsis and Streptomyces were tested for the degradation of aromatic compounds by growth in a liquid medium containing benzoate, monohydroxylated benzoates, or quinate as the principal carbon source. Benzoate was converted to catechol. The key intermediate in the degradation of salicylate was either catechol or gentisate, while m-hydroxybenzoate was metabolized via gentisate or protocatechuate. p-Hydroxybenzoate and quinate were converted to protocatechuate. Catechol, gentisate, and protocatechuate were cleaved by catechol 1,2-dioxygenase, gentisate 1,2-dioxygenase, and protocatechuate 3,4-dioxygenase, respectively. The requirement for glutathione in the gentisate pathway was dependent on the substrate and the particular strain. The conversion of p-hydroxybenzoate to protocatechuate by p-hydroxybenzoate hydroxylase was gratuitously induced by all substrates that were metabolized via protocatechuate as an intermediate, while protocatechuate 3,4-dioxygenase was gratuitously induced by benzoate and salicylate in two Amycolatopsis strains.

Topics: Actinomycetales; Benzoates; Benzoic Acid; Glutathione; Hydroxybenzoates; Parabens; Salicylates; Salicylic Acid; Streptomyces

The pH-dependence of efflux of salicylate and p-hydroxybenzoic acid (PHB) from human red cells indicates that the un-ionized species penetrates the membrane. No effect of the anion channel blocker 4,4'-diisothiocyano-2,2'-disulphonic stilbene was observed. The temperature-dependence of efflux suggests that the energy barrier to transport of salicylate and PHB is the transfer of the acids from water into the membrane, rather than transport through the membrane interior. Intracellular binding of both acids was found to be pH-dependent.

Topics: Biological Transport; Erythrocyte Membrane; Humans; Hydrogen-Ion Concentration; Hydroxybenzoates; In Vitro Techniques; Kinetics; Parabens; Prohibitins; Salicylates; Temperature

Electron microscopic and spectrophotometric studies showed that salicylate causes gross swelling of mitochondria in isotonic salt solutions. In overall morphology the salicylate-treated mitochondria resembled those from patients with Reye's syndrome. Salicylate analogs such as m-hydroxybenzoate, p-hydroxybenzoate, and benzoate did not exert this effect. The mitochondria deformed by salicylate tended to return to their original condensed form on removal of the drug.

Topics: Animals; Benzoates; Benzoic Acid; Hydroxybenzoates; Microscopy, Electron; Mitochondria, Liver; Mitochondrial Swelling; Parabens; Rats; Reye Syndrome; Salicylates

Topics: Anthelmintics; Mycobacterium tuberculosis; Parabens; Salicylates