Cerebral gustatory activation in response to free fatty acids using gustatory evoked potentials in humans.

There is some evidence of specific oro-detection of FFAs in rodents and humans. The aim of this study was to record gustatory evoked potentials (GEPs) in response to FFA solutions and to compare GEPs in response to linoleic acid solution with GEPs obtained after stimulation with sweet and salty tastants. Eighteen healthy men were randomly stimulated with fatty (linoleic acid), sweet (sucrose), and salty (NaCl) solutions at two concentrations in the first experiment. Control recordings (n = 14) were obtained during stimulation by a paraffin oil mixture without FFA or by water. In the second experiment, 28 men were randomly stimulated with five FFA solutions and a paraffin emulsion. GEPs were recorded with electroencephalographic electrodes at Cz, Fz, and Pz. GEPs were observed in response to FFA in all participants. GEP characteristics did not differ according to the quality and the concentration of the solutions in the first experiment and according to the FFA in the second experiment. This study describes for the first time GEPs in response to FFA and demonstrates that the presence of FFA in the mouth triggers an activation of the gustatory cortex. These data reinforce the concept that fat taste could be the sixth primary taste.

Identification of linoleic acid, a main component of the n-hexane fraction from Dryopteris crassirhizoma, as an anti-Streptococcus mutans biofilm agent.

Dryopteris crassirhizoma is a semi-evergreen plant. Previous studies have shown the potential of this plant as an agent for the control of cariogenic biofilms. In this study, the main antibacterial components of the plant were identified by correlating gas chromatography-mass spectrometry data with the antibacterial activity of chloroform and n-hexane fractions and then evaluating the activity of the most potent antibacterial component against Streptococcus mutans UA159 biofilms. The most potent antibacterial component was linoleic acid, a main component of the n-hexane fraction. Linoleic acid reduced viability in a dose dependent manner and reduced biofilm accumulation during initial and mature biofilm formation. Furthermore, when the biofilms were briefly treated with linoleic acid (10 min/treatment, a total of six times), the dry weight of the biofilms was significantly diminished. In addition, the anti-biofilm activity of the n-hexane fraction was similar to that of linoleic acid. These results suggest that the n-hexane fraction of D. crassirhizoma and linoleic acid may be useful for controlling cariogenic biofilms.

Antioxidant activity and inhibitory effects of lead (Leucaena leucocephala) seed extracts against lipid oxidation in model systems.

Antioxidant activity of brown lead (Leucaena leucocephala) seed extracts with and without prior chlorophyll removal was studied in comparison with mimosine. Both extracts showed similar hydroxyl radical (HO(•)) scavenging activity, hydrogen peroxide (H2O2) scavenging activity, singlet oxygen inhibition and hypochlorous acid (HOCl) scavenging capacity (p > 0.05). Nevertheless, the extract without prior chlorophyll removal had higher oxygen radical absorbance capacity than that with prior chlorophyll removal (p < 0.05). Generally, lead seed extracts with and without prior chlorophyll removal possessed a lower antioxidant activity, compared with mimosine. When lead seed extract without prior chlorophyll removal (100 and 200 ppm) was used in different lipid oxidation model systems, including ß-carotene-linoleic acid and lecithin liposome systems, the preventive effect toward lipid oxidation was dose-dependent. At the same level of use, mimosine exhibited a higher efficacy in prevention of lipid oxidation in both systems as indicated by the lower increases in thiobarbituric acid reactive substances. A similar result was obtained in minced mackerel. Therefore, lead seed extract containing mimosine could act as a natural antioxidant to prevent lipid oxidation in foods.

Linoleic acid and butyrate synergize to increase Bcl-2 levels in colonocytes.

The biological properties of polyunsaturated fatty acid (PUFA) classes have been the source of much contention. For example, n-3 PUFA are chemoprotective, whereas n-6 PUFA may promote tumor development. Since dietary components can have combinatorial effects, we further examined the apoptotic properties of n-3 or n-6 fatty acids when combined with different fiber sources. Mice were fed diets supplemented with either fish oil (FO; enriched in n-3 PUFA) or corn oil (CO; enriched in n-6 PUFA) and nonfermentable (cellulose) or fermentable (pectin) fiber sources. In complementary experiments, immortalized young adult mouse colonic (YAMC) cells were treated with docosahexaenoic acid (DHA; 22:6n-3) or linoleic acid (LA; 18:2n-6) with or without butyrate. Mice fed a FO and pectin diet had significantly (p < 0.05) increased levels of apoptosis in colonocytes compared to all other diets. Similarly, apoptosis was highly induced in DHA and butyrate cotreated YAMC cells. In contrast, in both YAMC and mouse models, LA/CO with butyrate/pectin treatment reduced apoptosis and enhanced expression of bcl-2. The LA and butyrate induced antiapoptotic phenotype was reversed by knocking down bcl-2 using targeted siRNA. In comparison, overexpression of bcl-2 blocked the proapoptotic effect of DHA and butyrate. These data provide new mechanistic insights into the regulation of apoptosis by dietary PUFA and fiber.

Human metabolite-derived alkylsuccinate/dilinoleate copolymers: from synthesis to application.

The advances in polymer chemistry have allowed the preparation of biomedical polymers using human metabolites as monomers that can hold unique properties beyond the required biodegradability and biocompatibility. Herein, we demonstrate the use of endogenous human metabolites (succinic and dilinoleic acids) as monomeric building blocks to develop a new series of renewable resource-based biodegradable and biocompatible copolyesters. The novel copolyesters were characterized in detail employing several standard techniques, namely 1H NMR, 13C NMR, and FTIR spectroscopy and SEC, followed by an in-depth thermomechanical and surface characterization of their resulting thin films (DSC, TGA, DMTA, tensile tests, AFM, and contact angle measurements). Also, their anti-fungal biofilm properties were assessed via an anti-fungal biofilm assay and the biological properties were evaluated in vitro using relevant human-derived cells (human mesenchymal stem cells and normal human dermal fibroblasts). These novel highly biocompatible polymers are simple and cheap to prepare, and their synthesis can be easily scaled-up. They presented good mechanical, thermal and anti-fungal biofilm properties while also promoting cell attachment and proliferation, outperforming well-known polymers used for biomedical applications (e.g. PVC, PLGA, and PCL). Moreover, they induced morphological changes in the cells, which were dependent on the structural characteristics of the polymers. In addition, the obtained physicochemical and biological properties can be design-tuned by the synthesis of homo- and -copolymers through the selection of the diol moiety (ES, PS, or BS) and by the addition of a co-monomer, DLA. Consequently, the copolyesters presented herein have high application potential as renewable and cost-effective biopolymers for various biomedical applications.

Potent in vitro Anti-mouth Cancer (KB) and Immunostimulating Activities of the Job's Tears (Coix lachryma-jobi Linn.) Seed Semi-purified Extract Cocktails Containing Linoleic Acid.

The crude methanolic and hexane extracts of non-cooked, steamed and roasted from three Job's Tears cultivars were prepared and further semi-purified by liquid-liquid extraction techniques and silica gel column. The six single semi-purified extracts (F1-F6) were combined as nine cocktails (CT1, CT6, CT8, CT13, CT14, CT21, CT24, CT25 and CT31) according to the IC50 values from the preliminary study and investigated for anti-proliferative and apoptotic induction on mouth cancer cell line (KB) and immunostimulating as well as antioxidative activities. The highest anti-proliferative activity was observed in CT13 showing the IC50 value of 0.53±0.45 µg/mL which was higher than 5-fluorouracil and doxorubicin of 20.34 and 1.60 times, respectively. CT1 which was the combination of F1-F6 and CT13 which was the combination of F4-F6 exhibited significant strong synergistic activity with the combination index value (CI) of 0.28. CT1 at 200 µg/mL showed the highest percentages of apoptotic cells (40.65±10.97%) with no necrotic cells, but lower than cisplatin (100 µg/mL) of 2.18 times. CT14 gave the highest immunostimulating activity with the phagocytosis percentage of 13.0±1.7%, but lower than lipopolysaccharide of 1.08 times. CT31 gave the highest free radical scavenging and metal chelating activities with the SC50 and MC50 values of 0.73±0.07 and 1.99±0.24 µg/mL, but lower than ascorbic acid and EDTA of 18.25 and 4.33 times, respectively. The linoleic acid contents related to anti-cancer activity were also examined by HPLC. This study has demonstrated that CT1 composing of F1-F6 at the percentage ratio of 0.71:2.06:81.38: 8.47:4.92:2.46 was the potential cocktails of the semi-purified extracts from the Job's Tears which can be further developed as a novel active compound for oral cancer treatment.

Anticancer activity of polymeric nanoparticles containing linoleic acid-SN38 (LA-SN38) conjugate in a murine model of colorectal cancer.

Biodegradable polymeric nanoparticles (NPs) have been used frequently as nanocarriers for anticancer drugs. Linoleic acid conjugated SN38 (LA-SN38)-loaded NPs (EBNPs) were developed using biodegradable poly (ethylene oxide)-poly (butylene oxide) (PEO-PBO) diblock copolymer by titration hydration method without using a toxic organic solvent. The EBNPs had high drug loading efficiency and entrapment efficiency for LA-SN38, at 7.53% and 93.55%, respectively. The polydispersity index (PDI) and average diameter were 0.173 ±â€¯0.019 and 226.1 ±â€¯1.2 nm, respectively. The transmission electron microscope (TEM) image presented that the NPs were homogeneous in size and had spherical structures. In vitro study showed the release behavior of EBNPs was slow and sustained. Furthermore, cytotoxicity and apoptosis assay proved that EBNPs were more effective in growth inhibition of human colon cancer cells. Cell uptake experiments further demonstrated that EBNPs could avoid the phagocytosis by macrophages and promote the uptake by cancer cells. In vivo, EBNPs had prolonged blood circulation time and tumor selectivity in biodistribution. The tumor inhibitory rate of EBNPs was higher compared to SNPs group and CPT-11group (P < 0.01), and the drug did not show significant systemic toxicity at the tested dose. These results indicated that EBNPs are a promising candidate for delivery of LA-SN38 to treat colorectal cancer.

Detection and modulation of capsaicin perception in the human oral cavity.

Capsaicin causes a burning or spicy sensation when this vanilloid compound comes in contact with trigeminal neurons of the tongue. This compound has low solubility in water, which presents difficulties in examining the psychophysical properties of capsaicin by standard aqueous chemosensory tests. This report describes a new approach that utilizes edible strips for delivering precise amounts of capsaicin to the human oral cavity for examining threshold and suprathreshold amounts of this irritant. When incorporated into pullulan-based edible strips, recognition thresholds for capsaicin occurred over a narrow range, with a mean value near 1 nmol. When incorporated into edible strips at suprathreshold amounts, capsaicin yielded robust intensity values that were readily measured in our subject population. Maximal capsaicin intensity was observed 20 s after strips dissolved on the tongue surface, and then decreased in intensity. Suprathreshold studies showed that complete blockage of nasal airflow diminished capsaicin perception in the oral cavity. Oral rinses with vanillin-linoleic acid emulsions decreased mean intensity values for capsaicin by approximately 75%, but only modestly affected recognition threshold values. Also, oral rinses with isointense amounts of aqueous sucrose and sucralose solutions decreased mean intensity values for capsaicin by approximately 50%. In addition, this decrease in capsaicin intensity following an oral rinse with sucrose was partially reversed by the sweet taste inhibitor lactisole. These results suggest that blockage of nasal airflow, vanillin, sucrose, and sucralose modulate capsaicin perception in the human oral cavity. The results further suggest a chemosensory link between receptor cells that detect sweet taste stimuli and trigeminal neurons that detect capsaicin.

Characterization of extracellular polymeric substance (EPS) fractions produced by Microcystis aeruginosa under the stress of linoleic acid sustained-release microspheres.

This paper focuses on the characterization of extracellular polymeric substances (EPS), which are composed of soluble EPS (SL-EPS), loosely bound EPS (LB-EPS), and tightly bound EPS (TB-EPS) produced by Microcystis aeruginosa under the stress of linoleic acid (LA) and LA sustained-release microspheres. Three-dimensional excitation-emission matrix (3D-EEM) fluorescence spectroscopy and Fourier transform infrared (FTIR) spectrometry were used to characterize three forms of EPS while the content of polysaccharide and protein was tested, respectively. The results showed that the highest inhibitor rate (IR) occurred when M. aeruginosa were exposed to LA sustained-release microspheres of 0.3 g L-1. The 3D-EEM contour demonstrated that tryptophan and protein-like substances were detected in all three EPS fractions, whereas humic acid-like substance was only distributed in SL-EPS, and aromatic proteins merely existed in LB-EPS and TB-EPS. The infrared spectrum showed that functional groups in three EPS fractions had no obvious change in all experimental groups. Polysaccharide (1120-1270 cm-1, C-O-C and C-O stretching vibration) and protein (1384-1670 cm-1, C-N and N-H stretching) were detected in three forms of EPS. Graphical abstract ᅟ.

Omega-3 and Omega-6 Fatty Acids Act as Inhibitors of the Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Activity.

Polyunsaturated fatty acids have been reported to play a protective role in a wide range of diseases characterized by an increased metalloproteinases (MMPs) activity. The recent finding that omega-3 and omega-6 fatty acids exert an anti-inflammatory effect in periodontal diseases has stimulated the present study, designed to determine whether such properties derive from a direct inhibitory action of these compounds on the activity of MMPs. To this issue, we investigated the effect exerted by omega-3 and omega-6 fatty acids on the activity of MMP-2 and MMP-9, two enzymes that actively participate to the destruction of the organic matrix of dentin following demineralization operated by bacteria acids. Data obtained (both in vitro and on ex-vivo teeth) reveal that omega-3 and omega-6 fatty acids inhibit the proteolytic activity of MMP-2 and MMP-9, two enzymes present in dentin. This observation is of interest since it assigns to these compounds a key role as MMPs inhibitors, and stimulates further study to better define their therapeutic potentialities in carious decay.

Three-dimensional spheroid cell model of in vitro adipocyte inflammation.

To improve treatment of obesity, a contributing factor to multiple systemic and metabolic diseases, a better understanding of metabolic state and environmental stress at the cellular level is essential. This work presents development of a three-dimensional (3D) in vitro model of adipose tissue displaying induced lipid accumulation as a function of fatty acid supplementation that, subsequently, investigates cellular responses to a pro-inflammatory stimulus, thereby recapitulating key stages of obesity progression. Three-dimensional spheroid organization of adipose cells was induced by culturing 3T3-L1 mouse preadipocytes on an elastin-like polypeptide-polyethyleneimine (ELP-PEI)-coated surface. Results indicate a more differentiated phenotype in 3D spheroid cultures relative to two-dimensional (2D) monolayer analogues based on triglyceride accumulation, CD36 and CD40 protein expression, and peroxisome proliferator-activated receptor-γ (PPAR-γ) and adiponectin mRNA expression. The 3T3-L1 adipocyte spheroid model was then used to test the effects of a pro-inflammatory microenvironment, namely maturation in the presence of elevated fatty acid levels followed by acute exposure to tumor necrosis factor alpha (TNF-α). Under these conditions, we demonstrate that metabolic function was reduced across all cultures exposed to TNF-α, especially so when pre-exposed to linoleic acid. Further, in response to TNF-α, enhanced lipolysis, monitored as increased extracellular glycerol and fatty acids levels, was observed in adipocytes cultured in the presence of exogenous fatty acids. Taken together, our 3D spheroid model showed enhanced adipogenic differentiation and presents a platform for elucidating the key phenotypic responses that occur in pro-inflammatory microenvironments that characterize obesogenic states.

Activation of tongue-expressed GPR40 and GPR120 by non caloric agonists is not sufficient to drive preference in mice.

There is mounting evidence that, in addition to texture and olfaction, taste plays a role in the detection of long chain fatty acids. Triglycerides, the main components of oils and dietary fat, are hydrolyzed in the mouth by a lingual lipase secreted from the von Ebner gland and the released free fatty acids are detected by the taste system. GPR40 and GPR120, two fatty acid responsive G-protein-coupled receptors (GPCRs), are expressed in taste bud cells, and knockout mice lacking either of those receptors have blunted taste nerve responses to and reduced preference for fatty acids. Here we investigated whether activation of those GPCRs is sufficient to elicit fat taste and preference. Five non-fatty acid agonists of GPR40 and two non-fatty acid agonists of GPR120 activated the glossopharyngeal nerve of wild-type mice but not of knockout mice lacking the cognate receptor. In human subjects, two-alternative forced choice (2-AFC) tests, triangle tests and sensory profiling showed that non fatty acid agonists of GPR40 dissolved in water are detected in sip and spit tests and elicit a taste similar to that of linoleic acid, whereas 2-AFC tests showed that two agonists of GPR120 in water are not perceived fattier than water alone. Wild-type mice did not show any preference for five agonists of GPR40, two agonists of GPR120 and mixtures of both agonists over water in two-bottle preference tests. Together these data indicate that GPR40 mediated taste perception is not sufficient to generate preference.

Antimicrobial activity of n-6, n-7 and n-9 fatty acids and their esters for oral microorganisms.

OBJECTIVE: This study is to assess the antibacterial activity of omega-6, -7, -9 (n-6, n-7, n-9) fatty acids against various oral microorganisms. METHODS: The n-6, n-7, n-9 fatty acids, such as gamma-linoleic acid (GLA), linoleic acid (LA), arachidonic acid (ARA), palmitoleic acid (PA), and oleic acid (OA), their fatty acid ethyl esters, GLA-EE, LA-EE, ARA-EE, PA-EE, OA-EE, and their fatty acid methyl esters, GLA-ME, LA-ME, ARA-ME, PA-ME, OA-ME, were investigated for antimicrobial activity against oral pathogens Streptococcus mutans, Candida albicans, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, and Porphyromonas gingivalis. Various concentrations of the fatty acids, their methyl and ethyl esters were tested against various oral pathogens in 96-well plates and blood-agar plate. The plates were incubated anaerobically or aerobically at 37 degrees C for 48h, and the colony forming units (CFU) were determined. RESULTS: The data demonstrated that select n-6, n-7, n-9 fatty acids and their esters exhibited strong antimicrobial activity against these oral microorganisms, demonstrating some specificity for individual microbial species. CONCLUSION: The potential use or the combinations of the n-6, n-7, n-9 fatty acids and/or their esters, provided in a local delivery vehicle to infected sites in the oral cavity, could be considered as an additional therapeutic approach to improving oral health.

Enhanced transdermal delivery of loratadine from the EVA matrix.

Various enhancers, such as fatty acids (saturated, unsaturated), glycerides, propylene glycols, and non-ionic surfactants, have been incorporated in the loratadine-EVA matrix to increase the rate of skin permeation of loratadine from an EVA matrix. The enhancing effects of these enhancers on the skin permeation of loratadine were evaluated using a modified Keshary-Chien cell fitted with intact excised rat skin. The penetration enhancers showed a higher flux, probably due to the enhancing effect on the skin barrier, the stratum corneum. Among the enhancers used, such as the fatty acids, glycols, propylene glycols, and non-ionic surfactants, linoleic acid showed the best enhancement. For the enhanced transdermal delivery of loratadine, application of an EVA matrix containing a permeation enhancer might be useful in the development of a transdermal drug delivery system.

In vitro prooxidant effect of caffeine.

Caffeine is a methylxanthine compound that acts as a stimulant in humans. It is the most widely consumed behaviourally active substance in the western world and it affects calcium influx and release in living cells. Caffeine is present in various substances such as tea, coffee and some medications. This article is focused on the impact of caffeine on oxidation. Caffeine promoted the peroxidation of linoleic acid emulsions used by 32.5, 48.9, and 54.3%, respectively, at 15, 30 and 45 microg/mL concentrations. Standard antioxidants such as alpha-tocopherol and trolox, a water-soluble analogue of tocopherol, inhibited 76.2 and 93.2% peroxidation of linoleic acid emulsion at 45 microg/mL concentration. Also, PC(50) value (caffeine concentration that produced a 50% increase in linoleic acid peroxidation) of caffeine was found to be 185 microM.

Preparation and evaluation of a linoleic-acid-modified amphiphilic polypeptide copolymer as a carrier for controlled drug release.

In the present study, we describe the synthesis, characterization and self-assembly of a novel amphiphilic linoleic acid (LA)-modified polypeptide copolymer and its drug release behavior in vitro as well. Initially, an amphiphilic ABA triblock copolymer comprising polytetrahydrofuran (PTHF) as a central hydrophobic block and poly(L-lysine)s as outer hydrophilic blocks was prepared via the ring-opening polymerization of epsilon-benzyloxycarbonyl-L-lysine N-carboxyanhydride with a distal amine-terminated PTHF as a macroinitiator, followed by the removal of the protecting group. The resulting triblock copolymer was then reacted with linoleic acid in the presence of N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCHCl)/N-hydroxysuccinimide (HOSu) to give rise to a target LA-modified polypeptide copolymer. It was found to self-assemble into nanoparticles in water. Its critical aggregation concentration was assessed by fluorescence measurement with N-phenyl-1-naphthylamine employed as a molecular probe. The particle sizes of the aggregates were determined by dynamic light scattering, and the aggregate morphologies were evidenced by transmission electron microscopy measurements. Finally, the drug-loading capacity and release behavior in vitro were investigated by using doxorubicin as a model drug.

Effects of emulsified octadecanic acids on gas production and cellulolysis by the rumen anaerobic fungus, Piromyces communis M014.

Responses of the rumen anaerobic fungus, Piromyces communis M014, to octadecanic long-chain fatty acids (LCFAs) were evaluated by measuring total and hydrogen gas productions, filter paper (FP) cellulose degradation and polysaccharidase enzyme activities. Octadecanic acids (stearic acid, C(18:0); oleic acid, C(18:1); linoleic acid, C(18:2) and linolenic acid, C(18:3)) were emulsified by ultrasonication under anaerobic conditions, and added to the medium at the level of 0.001%. When P. communis M014 was grown in culture with stearic and oleic acids, the cumulative gas production, FP cellulose digestion and enzyme activities were significantly (p<0.05) increased in the early incubation times relative to those for the control. However, the addition of linolenic acid inhibited all of the investigated parameters, including cellulose degradation, enzyme activities and gas production, up to 168h incubation. These results indicated that stearic and oleic acids tended to have stimulatory effects on fungal cellulolysis, whereas linolenic acid caused a significant (p<0.05) inhibitory effect on cellulolysis by the rumen fungus. The fungus, P. communis M014, can biohydrogenate C(18) unsaturated fatty acids to escape from their toxic effects. Therefore, in this study, the results indicated that the more highly the added C(18) LCFA to the fungal culture was unsaturated, the higher the inhibition of gas production and cellulase enzyme activity was.

Development and biopharmaceutical evaluation of quinupramine-EVA matrix containing penetration enhancer for the enhanced transdermal absorption in rats.

To increase the skin permeation of quinupramine through the rat skin, different types of enhancers were added to an ethylene-vinyl acetate (EVA) matrix containing 2% quinupramine. The effects of the enhancers on the level of quinupramine permeation through the skin were evaluated by using Franz diffusion cells that were fitted with the intact excised rat skin. Among the enhancers used, which included fatty acids (saturated and unsaturated), glycerides, pyrrolidones, and nonionic surfactants, polyoxyethylene-2-oleyl ether showed the best enhancement. The pharmacokinetics and bioavailability of quinupramine from an EVA matrix were examined to determine the level of percutaneous absorption in rats. The percutaneous absorption of quinupramine from the EVA matrix with or without an enhancer was investigated. Quinupramine was administered orally or intravenously to compare the pharmacokinetic parameters with that of the transdermal route. The relative bioavailability of quinupramine in the matrix containing polyoxyethylene-2-oleyl ether as an enhancer was approximately 2.81 times higher than the group without an enhancer. Histological examination revealed that the skin pretreated with the EVA matrix containing the enhancers had a loosely layered stratum corneum. These results show that the quinupramine-EVA matrix containing a permeation enhancer could be a good transdermal delivery system for providing sustained plasma concentrations.

Skin whitening effect of linoleic acid is enhanced by liposomal formulations.

Linoleic acid (LA) is known to have a whitening effect on hyperpigmented skin, and is encapsulated in liposomes for topical application because of its low solubility in aqueous solution, although the effect of liposomalization of LA on the whitening activity has not been evaluated. In the present study, we evaluated the effect of liposomalization on the whitening activity of LA by using LA in ethanol, hydrogel containing LA, and hydrogel containing liposomal LA towards the UV-stimulated hyperpigmented dorsal skin of brownish guinea pigs. The whitening effect was far greater for hydrogel containing liposomal LA (0.1% w/w as a final concentration of LA) than for free LA in ethanol or hydrogel containing LA. Next, the whitening effect of LA was examined with UV-stimulated hyperpigmented human upper arm skin by using a hydrogel containing liposomal LA (0.1% LA) and non-liposomal LA (3.0, 10.0% LA). Liposomal LA (0.1%) showed a whitening effect comparable to 10.0% non-liposomal LA and was far more effective than 3.0% non-liposomal LA. These results indicate that liposomal formulations are favorable for the transdermal application of LA.

Liposomes as fatty acids carriers in isolated rat liver: effect on energy metabolism and on isolated mitochondria activity.

The effects of fatty acids (FA)-carrier, egg-lecithin liposomes (LIPO) as alternative to BSA, on ATP, glycogen and glucose contents in isolated perfused liver of fed rats were non-invasively studied using 31P/13C nuclear magnetic resonance (NMR). Oxidative phosphorylation was studied in isolated mitochondria from the same liver consecutively to the NMR experiments. ATP content decreased slowly and ATP turnover was similar during the perfusion with saline solution (KHB) or LIPO. However, LIPO induced an enhancement of respiratory control ratio in isolated mitochondria. Tissue glycogen and glucose content decreased when FA (linoleate or linolenate) were perfused with defatted BSA (3%) or LIPO (600 mg/l) whereas glucose excretion level was unchanged and lactate excretion tended to increase, reflecting changes in the cytosolic redox state and/or an enhancement of glycolysis. Addition of FA (0.5 or 1.5 mM) to LIPO caused a dramatic fall in liver ATP, a mitochondrial uncoupling and an impairment of the phosphorylation activity. Perfusion with FA (1.5 mM) carried by BSA significantly increased the ATP degradation without change of mitochondrial function. Owing to the higher affinity of BSA than LIPO for FA, these latter could be more easily released from complex LIPO-FA, increasing their uncoupling effect. Hence, the FA concentrations have to be largely decreased from the above currently used concentrations to avoid this effect. It will then be possible to minimize the effector action of FA and to study their more specific metabolic function as fuel. It was concluded that LIPO were appropriate carriers to study the different metabolic effects of FA.