Amount Of Leukotriene B4 Research Articles

In vitro inhibition of 5-lipoxygenase by natural quinone compounds

Dual inhibition of cyclooxygenase (COX) and lipoxygenase (LOX) pathways is promising approach in treatment of inflammatory diseases. Drugs able to block production of prostanoids together with leukotrienes should provide better anti-inflammatory properties and fewer side effects than non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors [1,2]. Our previous studies revealed that some natural quinone compounds such as primin, alkannin, or shikonin are potent in vitro COX inhibitors [3]. In the current study, we tested 19 quinone compounds for 5-lipoxygenase (5-LOX) inhibition using in vitro assay according to [4] where neutrophile granulocytes with 5-LOX activity isolated from the human blood are incubated with arachidonic acid (substrate) and tested samples. After the incubation, the amount of leukotriene B4 (LTB4) is determined by commercial LTB4 EIA kit (Assay Designs). The most active quinone 5-LOX inhibitors were benzoquinone primin and naphthoquinone shikonin which decreased LTB4 production by 93 and 87% at 50µM concentration, respectively. Reference inhibitor zileuton reduced LTB4 production by 91% at the same concentration. Based on these preliminary results obtained in 5-LOX assay together with data from previous studies targeted on COX inhibition the plant quinones such as primin and shikonin should be considered for further studies aimed on their potential of dual COX/LOX inhibition.

Protein, cell, and LTB4 concentrations of lung edema fluid produced by high capillary pressures in rabbit

We previously demonstrated disruptions of the pulmonary capillary endothelium and alveolar epithelium at transmural pressures (Ptm) of 52.5 cmH2O in rabbit by electron microscopy. In the present study, we determined the characteristics of the alveolar edema fluid in this condition by carrying out bronchoalveolar lavage after blood perfusion for 10 min at Ptm of 12.5 (low), 32.5 (intermediate), and 52.5 cmH2O (high). At low Ptm, where our previous studies showed no ultrastructural changes, the volume of alveolar fluid obtained by urea dilution was very small, and the concentrations of proteins, cells, and leukotriene B4 (LTB4) in the bronchoalveolar lavage fluid (BALF) were low. However, at high Ptm the volume of alveolar fluid and the concentrations of total protein and cells in the BALF were greatly increased. The amount of LTB4 in the BALF also increased substantially from 6.0 to 49.5 micrograms (P < 0.001). Intermediate changes were seen at intermediate Ptm. We concluded that exposing pulmonary capillaries to high Ptm results in a high-permeability form of edema. In addition, the presence of LTB4 suggests that chemical mediators are released, possibly as the result of exposure of the reactive capillary endothelial basement membrane, as demonstrated by electron microscopy.

Effect of ingestion of eicosapentaenoic acid ethyl ester on carrageenan-induced colitis in guinea pigs

The effect of highly purified eicosapentaenoic acid ethyl ester (EPA-E) on colitis was investigated using a guinea pig model. The technique for preparing a degraded carrageenan with a molecular weight of about 30,000 from commercial ι-carrageenan was first refined. When this degraded carrageenan was fed to guinea pigs, localized ulcerations occurred in the cecum with infiltration of numerous mononuclear phagocytes. Oral administration of 300 mg · kg−1 · day−1 of EPA-E for 3 weeks significantly prevented the development of colitis. The amounts of prostaglandin E2, thromboxane B2, and leukotriene B4 released from the cecal mucosa were also measured. The release of prostaglandin E2 and thromboxane B2 was significantly decreased in the animals fed EPA-E compared with those given olive oil or a vehicle alone. In addition, there was a positive correlation between the amounts of these eicosanoids and the degree of ulcer formation. However, there was no difference in the amount of leukotriene B4 among various experimental groups of animals. Furthermore, EPA-E feeding induced a significant decrease in the level of arachidonic acid and a significant increase in that of EPA in peritoneal macrophages. These results suggest that EPA has a prophylactic effect on the development of carrageenan-induced colitis, which may be ascribed in part to reduced eicosanoid production.

Inflammatory Mediators in Postoperative Aphakic and Pseudophakic Baboon Eyes

We measured prostaglandin E2 and leukotriene B4 in the aqueous humor of baboon eyes, 1 or 8 days after phacoemulsification, with or without posterior chamber lens implantation. We also evaluated the effects of steroid eye drops and cyclooxygenase inhibitor eye drops on the synthesis of these mediators of inflammation. Eyes that had undergone phacoemulsification showed significant elevation of prostaglandin E2 at both postoperative periods compared with normal, phakic control eyes. The level of prostaglandin E2 was significantly (P less than .05) higher in eyes with posterior chamber lens implantation than in those without it, and was significantly (P less than .05) higher on the eighth than on the first postoperative day. The amount of leukotriene B4 was below the detection limit, except in the few eyes in which complications developed. Cyclooxygenase inhibitor eye drops significantly reduced the amount of prostaglandin E2 on both postoperative days, while steroid eye drops had no such effect.

Effect of dietary fish oils on the formation of leukotriene B4 and B5, thromboxane and platelet activating factor by rat leukocytes.

1. This study investigates the effect of dietary eicosapentaenoic acid (EPA), in the form of 'Max EPA' fish oil, on leukotriene B4 (LTB4) production in ionophore-stimulated rat leukocytes. Male Wistar rats (200-250 g) were fed for 3 weeks on a synthetic chow supplemented with either 10% by weight Max EPA oil or a coconut oil/safflower oil mixture. 2. The EPA-rich diet significantly increased the EPA content of leukocyte phospholipids and decreased the arachidonic acid level by 35% (P less than 0.001) compared with the control diet. 3. The concentration of leukotrienes in the ionophore (A23187) stimulated leukocytes was measured by reverse-phase HPLC using prostaglandin B2 as the internal standard. The EPA-supplemented diet caused a 50% decrease in LTB4 production (P less than 0.001) and a concomitant increase in the formation of the biologically less active LTB5 compared with the control diet. The amount of LTB4 and LTB5 produced by stimulated leukocytes closely resembled the changes in arachidonic acid and EPA content of leukocyte phospholipids. 4. Thromboxane B2 (TxB2) production in stimulated leukocytes from the EPA-fed animals was also decreased compared with the control group. 5. Although the formation of platelet activating factor by stimulated leukocytes was not altered by dietary treatment, the ability of an EPA-rich diet to decrease LTB4 and TxB2 production suggests that these diets may attenuate leukocyte activity and have useful anti-inflammatory effects.