• Nutritional Sciences
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• v.4 no.2
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• pp.73-78
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• 2001

This study investigated the effect of different dietary fats and fibers on colon tumor incidence and cell proliferation, the levels of eicosanoids and polyamines in colonic mucosa of DMH-treated rats. The experiment was conducted on male Sprague Dawley rats using a 2 $\times$3 factorial design with two fats (corn oil and DHA-rich fish oil) and two fibers (cellulose and pectin) and a fiber-free control. The rats were find an experimental diet containing 15% (w/w) dietary fat and 6% (w/w) fiber for 25 weeks. Tumor incidence was Bower in rats fed fish oil as opposed to corn oil. The levels of arachidonic acid (AA) and eicosanoids ($PGE_2, and TXB_2$) in normal colonic mucosa were significantly lower in rats fed fish oil and there was a concomitant increase of docosahexaenoic acid (DHA). The levels of eicosanoids and AA in tumor tissues were significantly higher than those of normal colonic mucosa. The level of polyamines in normal colonic mucosa was not affected by dietary fats but was significantly lower than that in rumor tissues. Dietary fiber did not have a significant effect on rumor incidence and the levels of AA, eicosanoids and polyamines. Overall, fish oil rich in DHA reduced cell prolifiration and thus inhibited colon carcinogenesis through its effect on the distribution of AA and production of eicosanoids in normal colonic mucosa. However, its effect on colon carcinogenesis revealed a lack of consistency depending on the type of dietary fiber in diet.

• BMB Reports
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• v.42 no.7
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• pp.401-410
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• 2009

We have developed a targeted lipidomics approach that makes it possible to directly analyze chiral eicosanoid lipids generated in cellular systems. The eicosanoids, including prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and alcohols (HETEs), have been implicated as potent lipid mediators of various biological processes. Enzymatic formations of eicosanoids are regioselective and enantioselective, whereas reactive oxygen species (ROS)-mediated formation proceeds with no stereo-selectivity. To distinguish between enzymatic and non-enzymatic pathways of eicosanoid formation, it is necessary to resolve enantiomeric forms as well as regioisomers. High sensitivity is also required to analyze the eicosanoid lipids that are usually present as trace amounts (pM level) in biological fluids. A discovery of liquid chromatography-electron capture atmospheric pressure chemical ionization/mass spectrometry (LC-ECAPCI/MS) allows us to couple normal phase chiral chromatography without loss of sensitivity. Analytical specificity was obtained by the use of collision-induced dissociation (CID) and tandem MS (MS/MS). With combination of stable isotope dilution methodology, complex mixtures of regioisomeric and enantiomeric eicosanoids have been resolved and quantified in biological samples with high sensitivity and specificity. Targeted chiral lipidomics profiles of bioactive eicosanoid lipids obtained from various cell systems and their biological implications have been discussed.

• Journal of Nutrition and Health
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• v.29 no.7
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• pp.703-712
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• 1996

This study planned to compare the effects of source and amount of dietary n-3 fatty acid, tuna oil and perilla oil, on lipid metabolism and eicosanoids production in Spargue-Dawley strain male rats. Weaning rats were fed 5 different experimantal diets for 4 weeks. (S : beef tallow 50%+sesame oil 50%, T1 : beef tallow 50%+sesame oil 40%+tuna oil 10%, T2 : beef tallow 50%+sesame oil 25%+tuna oil 25%, P1 : beef tallow 50%+sesame oil 40%+perilla oil 10%, P2 : beef tallow 50%+sesame oil 25%+perilla oil 25%) Food intake was higher in T2 group than in other groups, but body weight gain and food efficiency tate were not different among groups. Plasma total lipid and triglyceride were significantly lower in groups fed perilla oil as much as groups fed tuna oil than in S. But tuna oil reduced plasma cholesterol level more than perilla oil. Liver total lipid per unit, cholesterol and triglyceride were not affected by dietary fat sources. Peroxisomal $\beta$-oxidation was higher in T1 and T2 than in P1 and P2. Activities of glucose 6 phosphate dehydrogenase and malic enzyme were lower in T1 and T2 than in group fed sesame oil only. Plasma TXB2 was affected by n-3 fatty acid consumption, and it was lower in perilla oil groups as much as tuna oil groups than in S. But 6-keto PGF1$\alpha$ was not different among experimental groups. The results of this study indicated that tuna oil and perilla oil both decreased plasma lipids, however, the mechanism may be different. And tuna oil and perilla oil had a similar effects on eicosanoids production.

• Archives of Pharmacal Research
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• v.21 no.2
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• pp.120-127
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• 1998

Peroxisome proliferators induce hepatic peroxisome proliferation and hepatic tumors in rodents. These chemicals increase the expression of the peroxisomal $\beta$-oxidation pathway and the cytochrome P-450 4A family, which metabolizes lipids, including eicosanoids. Peroxisome proliferators transiently induce increased cell proliferation in vivo. However, peroxisome proliferators are weakly mitogenic and are not co-mitogenic with epidermal growth factor (EGF) in cultured hepatocytes. Earlier study found that the peroxisome proliferator ciprofibrate is cornitogenic with eicosanoids. In order to study possible mechanisms of the comitogenicity of peroxisome proliferator ciprofibrate and eicosanoids' we hypothesized that the co-mitogenicity may result from synergistic or additive increases of second messengers in mitogenic signal pathways. We therefore examined the effect of the peroxisome proliferator ciprofibrate, prostaglandin $F_2_{\alpha}$($PGF_2{\alpha}$) and the combination of ciprofibrate and $PGF_2{\alpha}$ with or without growth factors on the protein kinase C (PKC) activity, and inositol-1, 4, 5-triphosphate ($IP_{3-}$) and intracellular calcium ($[Ca^{2+}]_i$) concentrations in cultured rat hepatocytes. The combination of ciprofibrate and $PGF_2{\alpha}$ significantly increased particulate PKC activity. The combination of ciprofibrate and $PGF_2{\alpha}$ also significantly increased EGF, transforming growth factor-$\alpha$ ($TGF_2{\alpha}$) and hepatic growth factor (HGF)-induced particulate PKC activity. The combination of ciprofibrate and $PGF_2_\alpha$greatly increased $[Ca^{2+}]_i$. However, the increases of PKC activity and $[Ca^{2+}]_i$ by ciprofibrate and $PGF_2{\alpha}$ alone were much smaller. Neither ciprofibrate or $PGF_2{\alpha}$ alone nor the combination of ciprofibrate and $PGF_2{\alpha}$ significantly increased the formation of $IP_3$. The combination of ciprofibrate and $PGF_2{\alpha}$, however, blocked the inhibitory effect of $TGF-{\beta}$ on particulate PKC activity and formation of $IP_3$ induced by EGF. These results show that co-mitogenicity of the peroxisome proliferator ciprofibrate and eicosanoids may result from the increase in particulate PKC activity and intracellular calcium concentration but not from the formation of $IP_3$.

• Journal of Nutrition and Health
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• v.29 no.10
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• pp.1072-1079
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• 1996

This study was performed to elucidate the mechanism of dietary protein level on renal function through lipid and eicosanoids metabolism. Male rats of 337.8$\pm$5.7g body weight were undergone unilateral nephrectomy or sham-operation. The rats were divided into high protein(40% casein), normal protein(15% casein) and low protein(8% casein) diet groups and fed experimental diets ad libitum for 24 weeks. The results are summarized as follows. Serum total lipid, cholesterol and HDL-cholesterol of rats in 15% and 40% casein groups were higher than those of 8% casein group. But serum triglyceride was affected neither by uninephrectomy nor by dietary protein level. Serum thromboxane(TX) B2 and 6-keto prostaglandin F1$\alpha$ increased with increasing dietary protein level. Serum prostaglandin(PG) E2 was not affected by uninephrectomy nor by dietary protein level. Urinary PGE2 and TXB2 excretion tended to be lower in uninephrectomized groups. Renal tissue concentration of TXB2 was lower in uninephrectomized groups and in high protein group. These results suggest the possibility that the effects of dietary protein level on renal function could be due to changes in lipid and eicosanoids metabolism.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.364.2-364.2
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• 2002

(S) and (R) 12-HETE. endogenous eicosanoids. have recently been discovered to be implicated in a number of important biological activities. In particular. it has recently been reported by us that both the capsaicin-activated channel of sensory neurons and the cloned capsaicin receptor (VR1) are activated by the eicosanoids including these metabolites. We report herein a novel and efficient asymmetric synthesis of highly enantiomerically enriched 12(S)-HETE via enzymatic kinetic resolution of the key allylic alcohol synthon. (omitted)

• Proceedings of the Korean Nutrition Society Conference
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• 2002.05a
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• pp.91-91
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• 2002

• Journal of Nutrition and Health
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• v.34 no.8
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• pp.843-849
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• 2001

This study was performed to investigate the effect of n-3 fatty acids and dietary protein levels on renal function. Fifteen-month old male Sprague-Dawley rats were divided into 4 diet groups. Two-month old rats were used as a control group. The experimental diets contained either a% or 25% casein and lipid levels of the diets were 20% by weight. For the control group, the lipid was composed of beef tallow and corn oil on a 1:1 basis, and fish oil was comprised 75% of the fat mixture for the fish oil group. Rats were fed the diets ad libitum for 8 weeks. GFR and urinary protein excretion were higher in high protein groups, while fish oil exhibited no effects. Renal medulla TXB$_2$and PGE$_2$ concentrations tended to be higher in high protein groups and lower in fish oil groups. Light microscopic examinations showed that glomerulosclerosis, tubular atrophy, tubular cast, interstitial inflammation and interstitial fibrosis fended to be higher in aged rats and in high protein groups and lower in fish oil groups. Serum levels of total lipid, triglyceride and total cholesterol were higher in aged rats and lower in fish oil groups while serum HDL-cholesterol level was higher in young rats and in fish oil groups. However, dietary protein level had no effect on serum lipid levels. Serum TBARS concentration was higher in aged rats and in fish oil groups. In conclusion, fish oil caused changes in serum lipid concentrations and eicosanoids metabolism. The effect of fish oil on renal function was less obvious than dietary protein. However, fish oil seemed to be effective in lessening deterioration of renal function due to aging and/or high protein diets through changes in lipid and eicosanoids metabolism.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.525-530
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• 2000

During reperfusion of skeletal muscle after ischemia, lipid mediators, mainly eicosanoids, are released and may have a role in the pathogenesis of reperfusion injury. To validate the role of eicosanoids in the ischemia-reperfusion induced functional deficits in skeletal muscle, we compared muscle edema and the changes of eicosanoid concentration in the rat hind limb after ischemia-reperfusion injury by application of tourniquet. After 4 hours of ischemia, reperfusion was established for 4 hours by releasing tourniquet. To assess tissue damage, edema, and wet/dry weight ratios were determined and the eicosanoid concnentrations were measured by the HPLC. The muscle edema and the release of cyclooxygenase metabolites were not induced by the ischemia itself rather they were significantly increased by reperfusion. Indomethacin treatment ameliorated limb edema and decreased the release of $6-keto-PGF_{1{\alpha}},$ thromboxane $B_2,$ and $PGE_2$ inducedby reperfusion. But the inhibitory effect of indomethacin on edema (35%) was relatively low than the inhibitory effect on release of cyclooxygenase metabolites (up to 69%) by reperfusion. These results support the view that cyclooxygenase products may play a significant role in the formation of muscle injury by ischemia-reperfusion and suggest that nonsteroidal antiinflammatory agents might be partially beneficial to the management of acute limb ischemia-reperfusion injury.

• Proceedings of the Korean Society of Applied Entomolohy Conference
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• 2000.05a
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• pp.46-46
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• 2000