Administration Of Arachidonic Acid Research Articles

Protective Effects of Arachidonic Acid Against Paraquat-Induced Pulmonary Injury.

In this study, we aimed to study the effects of arachidonic acid (AA) on acute lung injury (ALI) caused by paraquat (PQ) in mice. Male Kunming mice were randomly divided into three groups: control group, PQ group, and PQ + AA group (n = 24). The mice in the PQ and PQ + AA groups received a single oral dose of 20mg/kg bodyweight PQ, and the mice of the PQ + AA group were challenged by 500mg/kg bodyweight AA posttreatment 2h after PQ administration. The results indicated that the administration of AA significantly increased the activity of superoxide dismutase (SOD), decreased the activity of myeloperoxidase (MPO), the content of malondialdehyde (MDA), and the level of lactate dehydrogenase (LDH). Pathological examination also revealed that AA effectively alleviated PQ-induced histological damage. Furthermore, AA significantly reduced PQ-induced upregulations of inflammatory mediators such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8. These results demonstrated that AA had effective protection against PQ-induced ALI.

Effect of long-term administration of arachidonic acid on n-3 fatty acid deficient mice

The effect of long-term oral administration of arachidonic acid (ARA, 240mg/kg/day) on brain function was assessed for mice maintained on an n-3 fatty acid adequate or deficient diet. The administration of ARA for 13 weeks resulted in an elevation of spontaneous motor activity, or the tendency thereof, in both the n-3 fatty acid adequate and deficient groups. However, the n-3 fatty acid deficient mice that were administered with ARA revealed marked deterioration in motor function in a motor coordination test. In the experiment to investigate changes over time, the motor activity of the ARA-administered group continued to increase mildly in n-3 deficient mice, although that of the control group showed a decrease involving habituation for both diet groups from the second week. The fatty acid composition of the brain at the end of the behavioral experiments indicated an increase in the levels of ARA and other n-6 fatty acids, as well as a decrease in the levels of docosahexaenoic acid. These results suggest that long-term administration of ARA causes an increase of futile spontaneous motor activity and the diminution of motor function by aggravation of n-3 fatty acid deficiency.

Effects of chronic administration of arachidonic acid on lipid profiles and morphology in the skeletal muscles of aged rats

Arachidonic acid (20:4n−6, ARA) is a major component of the cell membrane, whereas ARA-derived eicosanoids are formed when cells are damaged. Aging is associated with an accretion of oxidative stress in skeletal muscles. In this study, we examined the effects of chronic administration (13 weeks) of ARA (240mg/kg/day) on fatty acid composition, antioxidative status, and morphology of slow (soleus muscles) and fast (extensor digitorum longus muscles; EDL)-twitch muscles in aged rats (21 months old). The level of reactive oxygen species was higher in the EDL of ARA-administered rats than in that of control rats. ARA administration decreased the muscle cell volumes and increased the number of slow myosin heavy chain (MHC)-positive cells in the EDL. The relative content of MHC2X was increased whereas the relative content of MHC2B was decreased in the EDL of ARA-administered rats. These results suggest that ARA deposition in the fast-twitch muscle of aged rats reduced cell volume with an increase in oxidative stress.

Effects of Long-Term Oral Administration of Arachidonic Acid and Docosahexaenoic Acid on the Immune Functions of Young Rats

Natural killer (NK) cells have many functional activities, including cytotoxicity and the capacity to produce cytokines and chemokines. NK cell activity is regulated partly by eicosanoids, which are produced from arachidonic acid (ARA) and eicosapentaenoic (EPA) acid. In this study, we investigated the effects of long-term therapy with ARA or docosahexaenoic acid (DHA) on the cytotoxic effects of the NK cells of young rats, which were fed on a nonfish oil diet for two generations. Control oil, ARA (240 mg/kg BW/day) or DHA (240 mg/kg BW/day) were orally administrated to the rats for 13 weeks before determining the cytotoxic activity of NK cells from the spleen against YAC-1 mouse lymphoma cell line, as well as the plasma levels of docosanoids or eicosanoids and inflammatory cytokines. Long-term ARA administration significantly suppressed the cytotoxic activity of NK cells. Moreover, ARA administration significantly increased the plasma levels of ARA, prostaglandin (PG) E2, and PGD2. However, DHA administration did not produce any different effects compared with those in the control rats. Furthermore, the inflammatory cytokine levels were not affected by the administration of ARA or DHA. These results suggest that long-term ARA administration has an inhibitory effect on the tumor cytotoxicity of NK cells in rat spleen lymphocytes owing to the enhanced synthesis of PGE2 and PGD2 from ARA because of the elevated plasma ARA levels in young rats.

Arachidonic acid and lipoxin A4 as possible endogenous anti-diabetic molecules

In both type 1 and type 2 diabetes mellitus, increased production of pro-inflammatory cytokines and reactive oxygen species (ROS) occurs that induce apoptosis of β cells and cause peripheral insulin resistance respectively though the degree of their increased production is higher in type 1 and less in type 2 diabetes mellitus. Despite this, the exact mechanism(s) that lead to increased production of pro-inflammatory cytokines: interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and ROS is not known. Studies showed that plasma concentrations of arachidonic acid (AA) and lipoxin A4 (LXA4) are low in alloxan-induced type 1 diabetes mellitus in experimental animals and patients with type 2 diabetes mellitus. Prior administration of AA, eicosapentaenoic and docosahexaenoic acids (EPA and DHA, respectively) and transgenic animals that produce increased amounts of EPA and DHA acids were protected from chemical-induced diabetes mellitus that was associated with enhanced formation of LXA4 and resolvins, while protectin D1 ameliorated peripheral insulin resistance. AA, LXA4, resolvins and protectins inhibit IL-6 and TNF-α production and suppress ROS generation. Thus, AA and lipoxins, resolvins and protectins may function as endogenous anti-diabetic molecules implying that their administration could be useful in the prevention and management of both types of diabetes mellitus.

Paraoxonase1 deficiency in mice is associated with hypotension and increased levels of 5,6-epoxyeicosatrienoic acid

AimSerum paraoxonase 1 (PON1) is an HDL-associated lipolactonase and its association with hypertension is controversial. We studied the possible role of PON1 in blood pressure (BP) regulation, by using PON1 knockout (PON1KO) mice. Methods and resultsBoth, systolic and diastolic BPs were lower in PON1KO compared to WT mice. Hypotension detected in PON1KO is probably neither related to nitric oxide/guanylate cyclase-mediated vasodilation nor to angiotensin II or aldosterone-mediated vasoconstriction. Surprisingly, when challenged by high-salt diet, BP was further reduced in PON1KO mice. The later, pointed to a possible involvement of transient receptor potential vanilloid 4 (TRPV4), and indeed, administration of ruthenium red, a TRPV4 blocker, resulted in a sharp rise in BP. The protein levels of TRPV4 in kidneys of PON1KO were not higher than in WT. However, the renal level of 5,6-epoxyeicosatrienoic acid (5,6-EET), a TRPV4 specific agonist, was significantly higher in PON1KO compared with WT mice. 5,6-EET levels were further elevated under high-salt diet or administration of arachidonic acid. Injection of inhibitor of CYP450 epoxygenase resulted in increased BP in PON1KO mice. Injection of recombinant human PON1 resulted in elevation of BP and a concomitant reduction in renal content of 5,6-EET. PON1, in vitro, metabolized 5,6-EET, but not other EETs, to its corresponding diol. Vasodilation, blocked by excess of dietary K+ but not reversed by depletion of cellular Ca2+ stores, point to endothelial-derived hyperpolarization-like response. ConclusionThe present study shows causal, direct relationship between PON1 and blood pressure which is mediated, at least in part, by the regulation of 5,6-EET.

Efficacy and mechanism of action of arachidonic acid in the treatment of hamsters infected with Schistosoma mansoni or Schistosoma haematobium

We have recently shown that in vitro and in vivo exposure of Schistosoma mansoni and Schistosoma haematobium to 5–10mM arachidonic acid (ARA) induces parasite surface membrane disintegration and eventual attrition. Here we report on the optimum ARA dose and post-infection treatment time for maximum schistosome demise in hamsters. A series of four experiments for each schistosome species indicated that oral administration of ARA after patency led to a highly significant (P<0.02 to <0.001) reduction in worm burden accompanied by a significant (P<0.05) decrease in worm egg load. ARA-mediated attrition in vivo appeared to be associated with high titres of serum antibodies to tegumental antigens. In support, serum antibodies from patently infected and ARA-treated hamsters readily bound to the surface membrane of ARA-exposed adult worms, as judged by indirect membrane immunofluorescence. More importantly, addition of serum antibodies and peripheral blood mononuclear cells significantly enhanced ARA-mediated adult worm attrition in vitro. These data together show that the schistosomicidal effect of ARA in laboratory animals is enhanced by immune effectors and is highly efficacious and entirely safe.

Responses to arachidonic acid and other dilator agonists and their modification by inhibition of prostaglandin synthesis in the canine hindlimb.

The influence of indomethacin, in doses that completely inhibit the response to arachidonic acid, has been examined on canine hindlimb vascular responses to intra-arterial administration of bradykinin, histamine, nitroglycerin, isoprenaline and papaverine. The hindlimb was perfused at constant flow. Dose-response curves to intra-arterial administration of arachidonic acid (12 to 200 microgram kg-1), bradykinin (0.4 to 100 ng kg-1), histamine (1.8 to 120 ng kg-1), nitroglycerin (15 to 100 ng kg-1), isoprenaline (12 to 100 ng kg-1) and papaverine (1.2 to 160 microgram kg-1) (all n = 4) were compared before and 30 min after indomethacin (5 mg kg-1 i.v.). All the drugs produced dose-related decreases in hindlimb perfusion pressure. After indomethacin, responses for all dilator agonists except arachidonic acid, were significantly greater than control (P less than 0.05), both in terms of absolute (mmHg) or percent change. Dose-response curves after indomethacin had a left upward shift compared with control. Arachidonic acid responses were completely blocked by indomethacin. These findings suggest that indomethacin produces a non-specific increase in responsiveness of the hindlimb vascular bed to dilator substances, except arachidonic acid. The data presented do not support the hypothesis that the peripheral vasodilatation produced by bradykinin, nitroglycerin and histamine could be mediated by endogenous prostaglandin release.

Brain phospholipid arachidonic acid half-lives are not altered following 15 weeks of N-3 polyunsaturated fatty acid adequate or deprived diet

Previous studies have infused radiolabeled arachidonic acid (AA) into rat brains and followed AA esterification into phospholipids for up to 24 h; however, the half-life of AA in rat brain phospholipids is unknown. Eighteen day old rats were fed either an n-3 PUFA adequate or deprived diet for 15 weeks. Following the 15 weeks, 40 microCi of [(3)H] AA was injected intracerebroventricularly into the right lateral ventricle using stereotaxic surgery and returned to their dietary treatment. From 4-120 days after [(3)H] AA administration, brains were collected for chemical analyses. The half-life of AA in rat brain phospholipids was 44 +/- 4 days for the n-3 PUFA adequate group and 46 +/- 4 days for the n-3 PUFA deprived group, which closely approximates the predicted half-life previously reported, based on the rate of entry from the plasma unesterified pool, suggesting the plasma unesterified pool is a major contributor to brain uptake of AA. Furthermore, unlike a previous report in which the half-life of brain phospholipid docosahexaenoic acid (DHA) was increased in n-3 PUFA deprived rats, n-3 PUFA deprivation did not significantly alter the AA half-life, suggesting different mechanisms exist to maintain brain concentrations of AA and DHA.

Cysteinyl Leukotriene Receptor Antagonists Inhibit Tumor Metastasis by Inhibiting Capillary Permeability

We explored the possibility of the cysteinyl leukotriene receptor antagonists, pranlukast and montelukast, preventing tumor cell migration through both cerebral and peripheral capillaries. To study tumor cell migration through brain capillaries, male Fisher rats were cannulated via the cisterna magna under pentobarbital anesthesia. RCN9 cells labeled with a fluorescent marker PKH67 were intravenously administered following arachidonic acid administration into the subarachnoid space, and specimens of the central nervous system were collected every 30 min for 8 h. Arachidonic acid increased the fluid volume with elevated white blood cell and RCN9 cell counts. When given 2 h before arachidonic acid administration, pranlukast, but not montelukast, reduced the fluid volume and inhibited white blood cell and RCN9 cell extravasation through the brain capillary. In addition, a Lewis lung carcinoma metastasis model in mice was used to study the inhibitory effect of pranlu kast and montelukast against cancer cell extravasation through general capillaries. When mice were given food containing either pranlukast or montelukast, immediately after paw amputation, tumor metastasis was prevented by both drugs, and their survival was prolonged. These results show that pranlukast can inhibit tumor cell migration through both the brain and peripheral capillaries, whereas montelukast inhibits tumor cell migration only in the peripheral capillaries.

Attenuated PGI2synthesis in obese Zucker rats

In obesity, skeletal muscle blood flow during exercise (functional hyperemia) is impaired. We have indirectly demonstrated that an altered arachidonic acid metabolism is responsible for the impaired functional vasodilation in the obese Zucker rat (OZR), a model of obesity. In this study, we tested the hypothesis that there is an impaired release of PGI(2) due to a nitration of PGI(2) synthase (PGIS), which is associated with a decreased prostanoid receptor expression. PGI(2), PGE(2), and thromboxane A(2) (TXA(2)) release were determined in vitro using ELISA under basal conditions and in response to arachidonic acid (AA) administration (50 microM). Immunofluorescence of PGI(2) and TXA(2) receptors (IP and TP, respectively) was determined in dispersed vascular smooth muscle cells (VSMCs). Nitration of tyrosine residues of the PGIS enzyme was determined using immunoprecipitation and Western blot analysis. Following AA administration, PGI(2) and PGE(2) release were attenuated in OZR compared with lean Zucker rats (LZR; controls). Basal and AA-induced TXA(2) release were not significantly different between groups. IP and TP immunofluorescence were not significantly different between OZR and LZR groups. OZR exhibited elevated nitration of tyrosine residues of PGIS compared with LZR. These results suggest that alterations in the PGI(2) pathway (attenuated PGI(2) synthesis), and not the TXA(2) pathway (normal TXA(2) synthesis/no change in TP receptor expression), underlie the attenuated functional hyperemia in the OZR.

Rapid Modulation of μ-Opioid Receptor Signaling in Primary Sensory Neurons

Management of pain by opioid analgesics is confounded by central adverse effects that limit clinical dosages. Consequently, there is considerable interest to understand peripheral analgesic effects of opioids. The actions of opioids on peripheral sensory neurons have been difficult to study because of a general lack of effect of opioid agonists on nociceptor function in culture despite documented presence of opioid receptors. In this study, the micro-opioid receptor agonist, [D-Ala(2),N-MePhe(4),Gly-ol(5)]-enkephalin (DAMGO), did not alter guanosine 5'-O-(3-[(35)S]thio)-triphosphate (GTPgamma[(35)S]) binding, adenylyl cyclase activity, or neuropeptide release in primary cultures of rat trigeminal ganglion (TG). However, after brief exposure to bradykinin (BK), DAMGO stimulated GTPgamma[(35)S] binding and inhibited both prostaglandin E(2) (PGE(2))-stimulated adenylyl cyclase activity and BK/PGE(2)-stimulated neuropeptide release. The effect of BK was blocked by the B(2) antagonist HOE 140 [D-Arg[Hyp(3),Thi(5),D-Tic(7),Oic(8)]-bradykinin], but not by the B(1) antagonist, Lys-[Leu8]des-Arg9-BK, and was mimicked by the protease-activated receptor-2 agonist, Ser-Leu-Ile-Gly-Arg-Leu-NH(2), and by activation of protein kinase C (PKC) or by administration of arachidonic acid (AA). The enhanced responsiveness of micro-opioid receptor signaling by BK priming was blocked by both cyclooxygenase and PKC inhibitors; however, the effect of AA was blocked only by a cyclooxygenase inhibitor. The results indicate that micro-opioid receptor signaling in primary sensory TG neurons is enhanced by activation of phospholipase C-coupled receptors via a cyclooxygenase-dependent AA metabolite that is downstream of PKC.

Vascular wall–produced prostaglandin E2 exacerbates arterial thrombosis and atherothrombosis through platelet EP3 receptors

Prostanoids, bioactive lipids derived from arachidonic acid (AA), are important for vascular homeostasis. Among them, prostaglandin E2 (PGE2) enhances aggregation of platelets submaximally stimulated in vitro. This results from activation of EP3, one of the four PGE2 receptors, which decreases the threshold at which agonists activate platelets to aggregate. Although PGE2 altered venous thrombosis induced by administration of AA, its role in pathophysiopathological conditions has remained speculative. We report that arterial walls subjected to inflammatory stimuli produce PGE2. In several models, we show that PGE2 produced by the arterial wall facilitates arterial thrombosis. Next, we detected PGE2 in mouse atherosclerotic plaques. We demonstrate that this plaque-produced PGE2 is not altered and is still able to activate EP3. In addition, we present evidence that PGE2 can leave the plaque and activate EP3 on blood platelets. Consistent with these findings, we observed that atherothrombosis induced in vivo by mechanical rupture of the plaque was drastically decreased when platelets lacked EP3. In conclusion, PGE2 facilitates the initiation of arterial thrombosis and, hence, contributes to atherothrombosis. Inhibition of the platelet EP3 receptor should improve prevention of atherothrombosis.

Arachidonic acid preserves hippocampal neuron membrane fluidity in senescent rats

Previous studies indicate that long-term dietary supplementation with arachidonic acid (AA) in 20-month-old rats (OA) effectively restores performance in a memory task and the induction of long-term potentiation in the hippocampus to the level of young control animals (YC). The present study examined protein mobility using the live cell imaging technique “Fluorescent Recovery After Photobleaching (FRAP)” in YC, old control (OC) and OA neurons in hippocampal slice preparations. Three measures; mobile fraction (Mf), diffusion constant (D) and time constant (τ), were estimated among YC, OC and OA. Each of these parameters was significantly different between OC and YC, suggesting that membrane fluidity is lower in OC than in YC. In contrast, D and τ were comparable in OA and YC, indicating that hippocampal neuronal membranes supplemented with AA were more fluid than those in OC, whereas the fraction of diffusible protein in the bleached region remained smaller than in YC. Long-term administration of AA to senescent rats might help to preserve membrane fluidity and maintain hippocampal plasticity.

Effects of arachidonic acid on the spatial cognition of aged rats

Abstract: To examine the effects of arachidonic acid (AA) on age‐related cognitive deficits, Fischer 344 rats were given an AA‐supplemented powder diet for 12 weeks from 18.6 months old as part of the old AA (OA) group. Other age‐matched rats were fed a non‐AA‐supplemented powder diet as part of the old control (OC) group, and young rats were fed lab pellets as part of the young control (YC) group. When the aged rats reached 20.0 months old, all animals were tested for spontaneous activity in an open field, followed by the Morris water maze place and cue tasks. Escape latencies for the place task showed that the YC rats were fastest, and there was no difference between the OA and OC groups. However, the probe test and the first block of the cue task indicated that the OA rats remembered the location of an invisible platform better than the OC rats. Although the amount of hippocampal AA was larger in the OA rats than in the OC rats, the difference was not significant. The results showed that AA administration to aged animals may alleviate age‐related deficits in spatial cognition.

Arachidonic acid improves aged rats' spatial cognition

To examine the effects of arachidonic acid (AA) on age-related cognitive deficits, F-344 rats were administered with an AA-supplemented powder diet from 79 weeks of age (OA group). For comparison, we also used an age-matched control group of animals (OC group) that were fed with a non AA-supplemented powder diet. When the subjects reached 87 weeks old, they were trained for Morris water maze place and cue tasks. Escape latencies of the OA group on the place task were significantly shorter than those of the OC group in the latter half of training. The probe test showed that OA rats remembered the trained platform position significantly better than OC rats. In the cue task training, the OC group was significantly slower than the OA group at the beginning of training, but their performance soon matched with that of the OA group. Fatty acids in the hippocampi were measured after the behavioral testing. There was no difference in AA composition in hippocampal phospholipids between the OA and OC groups. However, regression analysis conducted on AA composition and place task performance showed a significant correlation between these two parameters. The present study suggests that AA administration to aged animals can alleviate age-related deficits in spatial cognition.

Sexual hormones utilize complex mechanisms to modulate sebocyte differentiation

Sexual hormones are important in the maintenance of human skin. Being the endocrine “brain” of the skin, the sebaceous gland is a major target of sexual hormones. While androgens stimulate sebocyte proliferation, estrogens do not to affect sebaceous gland growth. Regarding differentiation, androgens are expected to stimulate and estrogens to suppress sebaceous lipid synthesis, while estrogens, in vivo, enhance sebaceous lipogenesis in aged skin. The latter results have been disputed by current in vitro data indicating no direct effect of sexual hormones on sebocyte differentiation. To elucidate these contradictions we have investigated possible pathways which may be used by sexual hormones to modulate sebocyte differentiation in vitro. It has been postulated that androgen induction of lipogenesis requires the concomitant presence of peroxisome proliferator‐activated receptor (PPAR) ligands. We found that arachidonic acid (AA), the direct precursor of leukotriene B4, a natural PPARα ligand, and linoleic acid (LA), a natural PPARδ ligand, induce sebocyte enlargement, accumulation of lipid droplets in the cytoplasm, and nuclear fragmentation. The combined administration of testosterone and AA or LA slightly increased sebaceous lipogenesis. In contrast, synthetic PPAR ligands were unable to enhance sebaceous lipogenesis. Interestingly, AA synthesis in human sebocytes was significantly stimulated by the prostaglandins (PG) E2 and Δ15‐J2. On the other hand, PPARγ expression was downregulated by the phytoestrogen genistein. Interestingly, 17β‐estradiol has previously been shown to induce the metabolism of PGD2 to Δ12‐PGJ2, a natural PPARγ ligand. In addition, we found that 17β‐estradiol increases IGF‐I synthesis (+28%) and down‐regulates IGF‐IR expression (−37 to −48%), whereas IGF‐I significantly induces sebaceous lipogenesis. In conclusion, sexual hormones are not directly active but are likely to utilize complex mechanisms, including modified known pro‐inflammatory pathways, to modulate sebocyte differentiation.

Effects of valeryl salicylate, a COX-1 inhibitor, on models of acute inflammation in mice

The effect of valeryl salicylate (VS), an inhibitor of cyclooxygenase-1 (COX-1), was evaluated in arachidonic acid or croton oil-induced ear oedema and carrageenan-induced paw oedema in mice. Ear oedema was induced by topical administration of arachidonic acid (2 mg per ear; 20 μl) or croton oil (1 mg per ear; 20 μl) to the inner surface of the left ear and the change in the ear’s thickness was measured with a precision micrometer (Fisher, USA). VS significantly inhibited the arachidonic acid ear oedema after l h at doses of 1.5–45 μg per ear; however, only at the dose of 45 μg per ear was it able to significantly reduce the croton oil-induced oedema at 6 h. Paw oedema was induced by the injection of 25 μl of 1% carrageenan into the plantar aponeurosis of the right hind paw. The oedema was evaluated at 0.5, 1, 2, 4, 24, 48 and 72 h. Previously in our experiments, we observed two peaks in paw oedema formation: one at 2 h, in the early phase (0–4 h), and the other, occurring at 48 h after carrageenan injection, in the late phase (24–72 h). The pre-treatment with VS significantly reduced the paw oedema at 2 h, the same effect observed with celecoxib and indomethacin treatments. At 24 h, VS did not inhibit oedema but significantly increased it mainly at 48 h after carrageenan injection. These results showed that VS was pharmacologically active in these models and suggest that COX-1 may participate in the early and late phases of inflammation in the models studied.

Vascular permeabilization by intravenous arachidonate in the rat peritoneal cavity: antagonism by antioxidants

Arachidonic acid was investigated for its vascular permeabilizing potential in the rat peritoneal cavity and for its mechanism of action. The antagonistic potential of antioxidants (vitamin E, vitamin C and troxerutin) was also evaluated. Vascular permeability was equated to the rate of extravasation of Evans blue dye from plasma into the peritoneal cavity. Baseline permeability was linear up to 2 h, with a rate constant ( k) of 0.0031±0.0007 h −1. Intravenous arachidonate (from 30 μg/kg to 3 mg/kg) induced an immediate, dose-related and significant increase in permeability (ranging from 80% to 150%), which was comparable to the effect induced by similar doses of serotonin. Aspirin (10 mg/kg) reduced the arachidonate-induced permeability by 75%, but interestingly neither the stable thromboxane A 2 receptor agonist U46619 (prostaglandin H 2 endoperoxide epoxymethane) nor prostacyclin was able to increase peritoneal vascular permeability. In contrast, the permeabilizing action of arachidonic acid was very sensitive to antioxidant agents. Thus, vitamin C and the flavonoid compound troxerutin (100 mg/kg) fully abolished arachidonate-induced permeability, whereas vitamin E had only a partial effect (40–100% inhibition). In conclusion, intravenous administration of arachidonic acid strongly enhanced peritoneal vascular permeability in the rat, apparently via free radical generation. This rat peritoneal model can be used to evaluate the in vivo antinflammatory potential of antioxidant drugs.

Effects of arachidonic acid plus zinc on glucose disposal in genetically diabetic (ob/ob) mice.

The present study is designed to determine whether arachidonic acid (AA) plus zinc improves clinical signs of diabetes in genetically diabetic ob/ob mice. In the first study, effects of acute administration of AA plus zinc on glucose disposal were determined in ob/ob and lean mice (n = 6 each). In the second study, ob/ob and lean mice were treated with increasing doses of AA plus zinc for 2 weeks (n = 5 each). Postprandial and fasting blood glucose concentrations, three-hour-area-average above fasting glucose concentration (TAFGC), water and food intake, body weight and plasma insulin concentrations were measured. Acute administration of AA plus zinc significantly increased glucose disposal in ob/ob mice. In the second study, postprandial and fasting blood glucose concentrations, TAFGC, and water and food intake in ob/ob mice treated with AA plus zinc for 2 weeks were significantly decreased compared with those in mice given no AA. Plasma insulin concentrations in both lean and ob/ob mice were not changed by AA treatment in drinking water. AA plus zinc in drinking water is effective in decreasing blood glucose levels in obese mice. These results indicate that use of these compounds should be considered as a dietary supplement to control hyperglycaemia in patients with type II diabetes.