• Title/Summary/Keyword: Lipid alteration

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Effect of edaravone in diabetes mellitus-induced nephropathy in rats

  • Varatharajan, Rajavel;Lim, Li Xin;Tan, Kelly;Tay, Chai Sze;Teoh, Yi Leng;Akhtar, Shaikh Sohrab;Rupeshkumar, Mani;Chung, Ivy;Abdullah, Nor Azizan;Banik, Urmila;Dhanaraj, Sokkalingam A.;Balakumar, Pitchai
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.4
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    • pp.333-340
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    • 2016
  • Edaravone, a synthetic-free radical scavenger, has been reported to reduce ischemia-reperfusion-induced renal injury by improving tubular cell function, and lowering serum creatinine and renal vascular resistance. The present study investigated the effect of edaravone in diabetes mellitus-induced nephropathy in rats. A single administration of streptozotocin (STZ, 55 mg/kg, i .p.) was employed to induce diabetes mellitus in rats. The STZ-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Mean body weight, lipid alteration, renal functional and histopathology were analysed. Diabetic rats developed nephropathy as evidenced by a significant increase in serum creatinine and urea, and marked renal histopathological abnormalities like glomerulosclerosis and tubular cell degeneration. The kidney weight to body weight ratio was increased. Moreover, diabetic rats showed lipid alteration as evidenced by a significant increase in serum triglycerides and decrease in serum high-density lipoproteins. Edaravone (10 mg/kg, i .p., last 4-weeks) treatment markedly prevented the development of nephropathy in diabetic rats by reducing serum creatinine and urea and preventing renal structural abnormalities. In addition, its treatment, without significantly altering the elevated glucose level in diabetic rats, prevented diabetes mellitus-induced lipid alteration by reducing serum triglycerides and increasing serum high-density lipoproteins. Interestingly, the renoprotective effect of edaravone was comparable to that of lisinopril (5 mg/kg, p.o, 4 weeks, standard drug). Edaravone prevented renal structural and functional abnormalities and lipid alteration associated with experimental diabetes mellitus. Edaravone has a potential to prevent nephropathy without showing an anti-diabetic action, implicating its direct renoprotection in diabetic rats.

Effect of Lipid Peroxidation on the Fluidity of Erythrocyte Ghost and Phospholipid Liposomal Membranes

  • Han, Suk-Kyu;Kim, Min;Park, Yeong-Hun;Park, Eun-Ju;Lee, Jeong-Hee
    • Archives of Pharmacal Research
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    • v.15 no.4
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    • pp.309-316
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    • 1992
  • The effects of lipid peroxidation on the fluidity of the lipid bilayers of the human erythrocyte ghosts and egg-lecithin phospholipid liposomes have been studied. For the measurements of the peroxidation extent and the fluidity of the membranes, the thiobarbituric acid-reactive substances and the fluorescence depolarization of 1, 6-diphynyl-1, 3, 5-hexatriene labelled into the membrane were employed, respectively. The lipid peroxidation was performed in hypoxanthine/xanthine oxidase/ferrous ion, and hydrogen peroxide/ferrous ion systems. The results of these experiments show that both of the xanthine oxidase and hydrogen peroxide systems effectively. The lipid peroxidation decreased the fluidity of the membranes, especially at the very early stage of the peroxidation reaction. The decrease in the fluidity of membrane by the lipid peroxidation has been ascribed to the alteration of the polyunsaturated acyl chains of lipids and cross linkages among the membrane components. However, under drastic condition of lipid peroxidation, tdhe fluidity of the membrane rather increased possibly due to the deterioration of the membrane integrity by the peroxidation. Morphological change of the erythrocyte on peroxidation has also been observed.

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Differential Effects of Cod Proteins and Tuna Proteins on Serum and Liver Lipid Profiles in Rats Fed Non-Cholesterol- and Cholesterol-Containing Diets

  • Hosomi, Ryota;Maeda, Hayato;Ikeda, Yuki;Toda, Yuko;Yoshida, Munehiro;Fukunaga, Kenji
    • Preventive Nutrition and Food Science
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    • v.22 no.2
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    • pp.90-99
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    • 2017
  • Fish muscles are classified into white and red muscles, and the chemical composition of the two fish muscles have many differences. Few reports have assessed the health-promoting functions of white fish muscle proteins (WFP) and red fish muscle proteins (RFP). We therefore evaluated the mechanisms underlying the alteration of lipid profiles and cholesterol metabolism following the intake of WFP prepared from cod and RFP prepared from light muscles of tuna. Male Wistar rats were divided into six dietary groups: casein (23%), WFP (23%), and RFP (23%), with or without 0.5% cholesterol and 0.1% sodium cholate. Compared to the WFP-containing diet, the RFP-containing diet supplemented with cholesterol and sodium cholate significantly increased serum and liver cholesterol contents. However, in the RFP groups, an alteration in cholesterol metabolism including an increased tendency to excrete fecal sterols and hepatic cholesterol $7{\alpha}$-hydroxylase was related to the reduction of hepatic cholesterol contents. This phenomenon might be related to the tendency of an increased food intake in RFP-containing diets. These results highlight the differential effects of WFP and RFP on serum and liver lipid profiles of Wistar rats fed non-cholesterol- or cholesterol-containing diets under no fasting condition.

Effect of Diphtheria Toxin on the Phospholipase D activity and Free Fatty Acid Release in HepG2 Cells (HepG2 세포의 포스포리파제 D 활성과 자유 지방산 방출에 대한 디프테리아 독소의 영향)

  • Koh, Eun-Hie
    • Journal of the Korean Chemical Society
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    • v.59 no.1
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    • pp.22-30
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    • 2015
  • The effect of diphtheria toxin on cell membrane lipids was studied by examining the phospholipase D (PLD) activity and free fatty acids (FFA) release in HepG2 cells. The diphtheria toxin effects on lipid alteration show apparently maximal at pH 5.1, stimulating PLD activity nearly 3.5 fold and enhancing FFA release approximately 5 fold over the control. These results indicate that the membrane is perturbed and its lipid component is rearranged during the diphtheria toxin translocation. Digitonin, a random membrane perturbing detergent, exhibit about four-fold higher perturbation effect over the diphtheria toxin at neutral pH. This observation suggests that the membrane perturbation induced by diphtheria toxin appears to be rather selective. To investigate the cause of the membrane perturbation, Cibacron blue, an inhibitor of membrane pore formation, and hemagglutinin, an influenza virus with fusion peptide, were tested for their effects on diphtheria toxin action. Cibacron blue decreased the diphtheria toxin effect by almost 50%, but the lipid alteration induced by hemagglutinin was similar to the diphtheria toxin effect. These observations imply that the membrane perturbation induced by diphtheria toxin may be caused by a combination of pore formation and insertion of hydrophobic peptide of toxin to the membrane as well. Additionally, we found that the diphtheria toxin increased the HepG2 cells permeability but the cells viability was maintained at high level at the same time. DNA fragmentation which is related to apoptosis was not induced by the toxin. Under these conditions, we could demonstrate that the lipid alteration of HepG2 cells was brought about by diphtheria toxin at acidic pH.

Effect of Rosiglitazone on Myocardial Ischemia-Reperfusion Injury in Rat Heart

  • Ha, Ki-Chan
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.4
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    • pp.181-186
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    • 2006
  • This study was undertaken to evaluate whether peroxisome proliferator-activated-receptor-gamma $(PPAR-{\gamma})$ agonist-rosiglitazone (ROSI) induces postischemic functional recovery in Langendorf heart model. Hearts isolated from normal rats were subjected to 20 min of normoxia or 25 min zero-flow ischemia followed by 50 min reperfusion. In this acute protocol, ROSI $(20\;{\mu}g/ml)$ administered 10 min before ischemia had no effect on hemodynamic cardiac function, but had protective effect on lipid peroxidation in in vitro experiments. In chronic protocol in which ROSI was given by daily gavage (4 mg/kg) for three consecutive days, ROSI could not prevent the hemodynamic alteration on cardiac performance, but has protective effect on the activity of superoxide dismutase (SOD). There was no significant difference in the contents of reduced glutathione (GSH) and catalase activity between ischemia-reperfusion (IR) and ROSI treated IR hearts. Although ROSI had no effect on hemodynamic factor, it had effect on antioxidant activity. Our results indicate that ROSI provides partial beneficial effects by inhibiting lipid peroxidation and/or recovering normal level of SOD activity in the ischemic reperfused heart.

Effects of Dietary Ca Levels and Kinds of Lipids on the Lipid Metabolism in the Rats (식이내 Ca 수준과 지방 종류를 달리하였을 때 흰쥐의 체내 지방대사에 미치는 영향)

  • 권오란
    • Journal of Nutrition and Health
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    • v.21 no.5
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    • pp.324-332
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    • 1988
  • Effects of a change in dietary Ca content and an alteration in dietary lipid type on lipid metabolism have been investigated in male Sprague-Dawley rats. The results obtained were summarized as follows ; 1) There was no comparable changes in food consumption and body weight gain among all 9 groups. 2) Serum total lipids and cholesterol were lowest when high Ca-corn all diet was fed, and highest when low Ca-butter diet was fed. 3) The contents of total lipids and cholesterol per g liver and total liver showed no consistent tendency with the dietary treatment. 4) Addition of Ca to the diet caused the significant increase in the dry fecal matter and fecal Ca. And fecal total lipids and fecal cholesterol were much greater if the high-Ca diet was fed than if control and low-Ca diet were fed. It is concluded that Ca and polyunsaturated acids have tendency of hypocholesterolemic effect.

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Scavenging Effects of Free Radicals and Inhibitory Effects of Lipid Peroxidation of Bupleury Radix Aqua-Acupuncture Solution in Vitro (시호 약침제제의 자유기 소거능 및 지질과산화 억제효능에 관한 연구)

  • Moon Jin-Young;Lim Jong-Kook
    • Journal of Acupuncture Research
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    • v.15 no.2
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    • pp.135-145
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    • 1998
  • Bupleury radix has been used for the treatment of fever, liver disease, inflammation in traditional medicine. The present study was carried out to evaluate the antioxidant effects of Bupleury radix aqua-acupuncture solution (BRAS) in vitro. Oxygen derived free radicals produced in the course of normal aerobic life, such as superoxide anion radical($O_2^-$ ), hydroxyl radicaI( OH), hydrogen peroxide($H_2O_2$) and singlet oxygen($^1O_2$) can attack polyunsaturated fatty acid in cell membranes, enzymes, other cell compounds, and give rise to lipid peroxidation, DNA damage, lipofuscin accumulation, structure alteration of cell membrane and cell death. In this study, antioxidant effects of BRAS on lipid peroxidation were determined according to the method of TBA. BRAS inhibited markedly peroxidation of linoleic acid during the autoxidation, and also inhibited lipid peroxidation induced by hydroxyl radical derived from $H_2O_2-Fe^{2+}$ in rat liver homogenate. And BRAS showed 30% scavenging effect on DPPH radical, also exhibited a 30% inhibitory effect on superoxide generation from xanthine-xanthine oxidase system. In addition, BRAS protected the cell death induced by tert-butyl hydroperoxide(t-BHP) and significantly increased cell viability in the normal rat liver cell(Ac2F).

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Effects of Calcium Intake on Lipid Contents and Enzyme Activity in Rats of Different Ages (연령이 다른 흰쥐에 있어 칼슘이 섭취수준이 체내 지질함량과 효소활성에 미치는 영향)

  • 최미경
    • Journal of the East Asian Society of Dietary Life
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    • v.8 no.1
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    • pp.9-19
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    • 1998
  • The purpose of this study was to investigate the effect of calcium intake on lipid contents and enzyme activities in rats of different ages. Lipid levels in serum and liver and GOT, CPK and LDH activities in serum were compared in rats of different ages(4 weeks and 10 months) that were fed various levels of calcium(50, 100, 200% of requirement)for 3 weeks. Body weight gain and feed efficiency ratio were significantly higher in young rats than in adults. Serum calcium level was increased by elevation of calcium intake levels were decreased. Liver phospholipid and triglyceride levels in the high-cal-terol and triglyceride levels were decreased. Liver phospholipid and triglyceride levels in the high calcium group were significantly lower than those in other groups. Serum GOT and LDH activities of adults were significantly higher in low-calcium group than those in adequate/high-calcium groups. However, serum CPK activity of adults was significantly higher in high-calcium group than that in low/adequate-calcium groups. The results of this study suggest that adequate calcium intake may have protective effects ont he alteration of lipid and enzyme activity in rats.

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Effect of Trolox C on CYP450 Isozymes Activity and Expression in Hepatic Ischemia/Reperfusion

  • Eum, Hyun-Ae;Kim, Sung-Ho;Lee, Sun-Mee
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.301.2-301.2
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    • 2002
  • The present study was done to determine the effect of trolox C. a hydrophilic analogue of vitamin E. on alteration in cytochrome P-450 (CYP)-dependent drug metabolism during ischemia and reperfusion. Rats were subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Rats were treated intravenously with trolox C (2.5 mg/kg) or vehicle (PBS. pH 7.4), 5 min before reperfusion. Serum alanine aminotransferase and lipid peroxidation levels were markedly increased after ischemia and reperfusion. This increase was significantly suppressed by trolox C. (omitted)

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Trolox C Ameliorates Hepatic Drug Metabolizing Dysfunction After Ischemia/Reperfusion

  • Eum, Hyun-Ae;Lee, Sang-Ho;Lee, Sun-Mee
    • Archives of Pharmacal Research
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    • v.25 no.6
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    • pp.940-945
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    • 2002
  • The present study was done to determine the effect of trolox C, a hydrophilic analogue of vitamin E, on hepatic injury, especially the alteration in cytochrome P-450 (CYP)-dependent drug metabolism during ischemia and reperfusion (I/R). Rats were subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Rats were treated intravenously with trolox C (2.5 mg/kg) or vehicle (PBS, pH 7.4), 5 min before reperfusion. Serum alanine aminotransferase and lipid peroxidation levels were markedly increased after I/R. This increase was significantly suppressed by trolox C. Cytochrome P-450 content was decreased after I/R but was restored by trolox C. There were no significant differences in ethoxyresorufin O-dealkylase (CYP 1A1) and methoxyresorufin O-dealkylase (CYP 1A2) activities among any of the experimental groups. Pentoxyresorufin O-dealkylase (CYP 2B1) activity was decreased and aniline p-hydroxylase (CYP 2E1) activity was increased after I/R. Both these changes were prevented by trolox C. Our findings suggest that trolox C reduces hepatocellular damage as indicated by abnormalities in microsomal drug-metabolizing function during I/R, and that this protection is, in part, caused by decreased lipid peroxidation.