• Title/Summary/Keyword: P450 2J2

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Ginsenoside Rk1 ameliorates paracetamol-induced hepatotoxicity in mice through inhibition of inflammation, oxidative stress, nitrative stress and apoptosis

  • Hu, Jun-Nan;Xu, Xing-Yue;Li, Wei;Wang, Yi-Ming;Liu, Ying;Wang, Zi;Wang, Ying-Ping
    • Journal of Ginseng Research
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    • v.43 no.1
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    • pp.10-19
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    • 2019
  • Background: Frequent overdose of paracetamol (APAP) has become the major cause of acute liver injury. The present study was designed to evaluate the potential protective effects of ginsenoside Rk1 on APAP-induced hepatotoxicity and investigate the underlying mechanisms for the first time. Methods: Mice were treated with Rk1 (10 mg/kg or 20 mg/kg) by oral gavage once per d for 7 d. On the 7th d, allmice treated with 250mg/kg APAP exhibited severeliverinjury after 24 h, and hepatotoxicitywas assessed. Results: Our results showed that pretreatment with Rk1 significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor, and interleukin-$1{\beta}$ compared with the APAP group. Meanwhile, hepatic antioxidants, including superoxide dismutase and glutathione, were elevated compared with the APAP group. In contrast, a significant decrease in levels of the lipid peroxidation product malondialdehyde was observed in the ginsenoside Rk1-treated group compared with the APAP group. These effects were associated with a significant increase of cytochrome P450 E1 and 4-hydroxynonenal levels in liver tissues. Moreover, ginsenoside Rk1 supplementation suppressed activation of apoptotic pathways by increasing Bcl-2 and decreasing Bax protein expression levels, which was shown using western blotting analysis. Histopathological observation also revealed that ginsenoside Rk1 pretreatment significantly reversed APAP-induced necrosis and inflammatory infiltration in liver tissues. Biological indicators of nitrative stress, such as 3-nitrotyrosine, were also inhibited after pretreatment with Rk1 compared with the APAP group. Conclusion: The results clearly suggest that the underlying molecular mechanisms in the hepatoprotection of ginsenoside Rk1 in APAP-induced hepatotoxicity may be due to its antioxidation, antiapoptosis, anti-inflammation, and antinitrative effects.

Stem cell-secreted 14,15-epoxyeicosatrienoic acid rescues cholesterol homeostasis and autophagic flux in Niemann-Pick-type C disease

  • Kang, Insung;Lee, Byung-Chul;Lee, Jin Young;Kim, Jae-Jun;Sung, Eun-Ah;Lee, Seung Eun;Shin, Nari;Choi, Soon Won;Seo, Yoojin;Kim, Hyung-Sik;Kang, Kyung-Sun
    • Experimental and Molecular Medicine
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    • v.50 no.11
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    • pp.8.1-8.14
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    • 2018
  • We previously demonstrated that the direct transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the dentate gyrus ameliorated the neurological symptoms of Niemann-Pick type C1 (NPC1)-mutant mice. However, the clinical presentation of NPC1-mutant mice was not fully understood with a molecular mechanism. Here, we found 14,15-epoxyeicosatrienoic acid (14,15-EET), a cytochrome P450 (CYP) metabolite, from hUCB-MSCs and the cerebella of NPC1-mutant mice and investigated the functional consequence of this metabolite. Our screening of the CYP2J family indicated a dysregulation in the CYP system in a cerebellar-specific manner. Moreover, in Purkinje cells, CYP2J6 showed an elevated expression level compared to that of astrocytes, granule cells, and microglia. In this regard, we found that one CYP metabolite, 14,15-EET, acts as a key mediator in ameliorating cholesterol accumulation. In confirming this hypothesis, 14,15-EET treatment reduced the accumulation of cholesterol in human NPC1 patient-derived fibroblasts in vitro by suppressing cholesterol synthesis and ameliorating the impaired autophagic flux. We show that the reduced activity within the CYP system in the cerebellum could cause the neurological symptoms of NPC1 patients, as 14,15-EET treatment significantly rescued cholesterol accumulation and impaired autophagy. We also provide evidence that the intranasal administration of hUCB-MSCs is a highly promising alternative to traumatic surgical transplantation for NPC1 patients.

Effect of Granite Porphyry Supplementation on Growth Performance and Meat Sensory Quality in Broiler Chickens (맥반석의 첨가 급여가 육계에서 성장성적 및 관능적 특성에 미치는 영향)

  • Choi T. H.;Kim D. W.;Ahn S. M.;You S. J.;Kim S. K.;An B. K.;Kang C. W.
    • Korean Journal of Poultry Science
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    • v.31 no.3
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    • pp.151-155
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    • 2004
  • This experiment was conducted to investigate the influence of dietary supplementation of granite porphyry (GP) on growth performances and meat sensory quality in commercial broiler chicks. A total of four hundred-fifty 5-day-old male broiler chicks were divided into 15 pens and fed one of five experimental diets for 5 weeks; 0% GP with antibiotics (Control), 1% GP with or without antibiotics, and 2% GP with or without antibiotics. Final body weight and daily weight gain of all GP supplemented groups were slightly higher than those of control. Feed conversion rate was improved in GP 1 % supplemented groups, although there was no significant difference. Feeding antibiotics in addition to GP did not influence the growth parameters. Relative weights of liver and abdominal fat tended to be reduced in broiler chickens fed GP supplemented diets. Feeding of 2% GP diet resulted in a significant improvement in meat sensory quality in terms of taste and tenderness(P < 0.05), but the effect of the 1% GP on meat sensory quality was not significant. The results of this study indicate that GP could be used as a favorable feed additive for production of sensory-enhanced broiler meats.

Analysis of Image Distortion on Magnetic Resonance Diffusion Weighted Imaging

  • Cho, Ah Rang;Lee, Hae Kag;Yoo, Heung Joon;Park, Cheol-Soo
    • Journal of Magnetics
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    • v.20 no.4
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    • pp.381-386
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    • 2015
  • The purpose of this study is to improve diagnostic efficiency of clinical study by setting up guidelines for more precise examination with a comparative analysis of signal intensity and image distortion depending on the location of X axial of object when performing magnetic resonance diffusion weighted imaging (MR DWI) examination. We arranged the self-produced phantom with a 45 mm of interval from the core of 44 regent bottles that have a 16 mm of external diameter and 55 mm of height, and were placed in 4 rows and 11 columns in an acrylic box. We also filled up water and margarine to portrait the fat. We used 3T Skyra and 18 Channel Body array coil. We also obtained the coronal image with the direction of RL (right to left) by using scan slice thinkness 3 mm, slice gap: 0mm, field of view (FOV): $450{\times}450mm^2$, repetition time (TR): 5000 ms, echo time (TE): 73/118 ms, Matrix: $126{\times}126$, slice number: 15, scan time: 9 min 45sec, number of excitations (NEX): 3, phase encoding as a diffusion-weighted imaging parameter. In order to scan, we set b-value to $0s/mm^2$, $400s/mm^2$, and $1,400s/mm^2$, and obtained T2 fat saturation image. Then we did a comparative analysis on the differences between image distortion and signal intensity depending on the location of X axial based on iso-center of patient's table. We used "Image J" as a comparative analysis programme, and used SPSS v18.0 as a statistic programme. There was not much difference between image distortion and signal intensity on fat and water from T2 fat saturation image. But, the average value depends on the location of X axial was statistically significant (p < 0.05). From DWI image, when b-value was 0 and 400, there was no significant difference up to $2^{nd}$ columns right to left from the core of patient's table, however, there was a decline in signal intensity and image distortion from the $3^{rd}$ columns and they started to decrease rapidly at the $4^{th}$ columns. When b-value was 1,400, there was not much difference between the $1^{st}$ row right to left from the core of patient's table, however, image distortion started to appear from the $2^{nd}$ columns with no change in signal intensity, the signal was getting decreased from the $3^{rd}$ columns, and both signal intensity and image distortion started to get decreased rapidly. At this moment, the reagent bottles from outside out of 11 reagent bottles were not verified from the image, and only 9 reagent bottles were verified. However, it was not possible to verify anything from the $5^{th}$ columns. But, the average value depends on the location of X axial was statistically significant. On T2 FS image, there was a significant decline in image distortion and signal intensity over 180mm from the core of patient's table. On diffusion-weighted image, there was a significant decline in image distortion and signal intensity over 90 mm, and they became unverifiable over 180 mm. Therefore, we should make an image that has a diagnostic value from examinations that are hard to locate patient's position.

Comparison of Growth, Milk Yield and Draughtability of Murrah-Philippine Crossbred and Philippine Native Buffaloes

  • Salas, R.C.D.;van der Lende, T.;Udo, H.M.J.;Mamuad, F.V.;Garillo, E.P.;Cruz, L.C.
    • Asian-Australasian Journal of Animal Sciences
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    • v.13 no.5
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    • pp.580-586
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    • 2000
  • Data collected between 1981 and 1991 at the Philippine Carabao Center at Central Luzon State University (PCC-CLSU) were used for the comparison of growth, milk yield and draughtability of Murrah-Philippine crossbred and Philippine native buffaloes. Body weights and body measurements were available at 3-month intervals from birth to 36 months of age for a total of 34 $Murrah{\times}Philippine$ native buffalo F1 crossbreds (CBB; 21 cows, 13 bulls) and 32 Philippine native buffaloes (PNB; 16 cows, 16 bulls). Lactation records were available for 14 CBB and 19 PNB cows. Data for draughtability under wet and dry ploughing conditions were available for 4 CBB and 4 PNB steers. The results indicate that crossbreds grow faster (0-9 months of age: cows $442{\pm}19$ vs. $301{\pm}21g/day$, bulls $305{\pm}23$ vs. $296{\pm}21g/day$; 9-36 months of age: cows $227{\pm}10$ vs. $147{\pm}12g/day$, bulls $282{\pm}13$ vs. $138{\pm}12g/day$), mature earlier and produce more milk (1st lactation: $1139{\pm}153$ vs. $450{\pm}112kg$; 2nd lactation: $1115{\pm}132$ vs. $488{\pm}136kg$) than native buffaloes, but have a poorer draughtability (wet ploughing; force as % of body weight $8.8{\pm}0.2$ vs. $12.2{\pm}0.6$; dry ploughing: cut depth $10.98{\pm}0.25$ vs. $11.92{\pm}0.13cm$, velocity $0.50{\pm}0.03$ vs. $0.60{\pm}0.02m/sec$, force as % of body weight $9.0{\pm}0.6$ vs. $11.3{\pm}0.7$). The correlation coefficients between body weight and body measurements at birth and at 3-month intervals indicate that heart girth has a relatively high correlation with body weight, especially in crossbreds. It is concluded that in Philippine smallholder farming systems in which meat and milk production are secondary to draught power, the native buffalo is preferable from the point of view of input needed to maintain the number of animals kept for a required draught force.