• Title/Summary/Keyword: hepatic

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Alteration of Hepatic 3'-Phosphoadenosine 5'-phosphosulfate and Sulfate in ICR Mice by Xenobiotics that are Sulfated

  • Kim, Hyo-Jung;Oh, Mi-Hyune;Sunwoo, Yu-Sin;Seo, Kyung-Won;Park, In-Won;Moon, Byung-Won
    • Biomolecules & Therapeutics
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    • v.3 no.1
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    • pp.85-90
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    • 1995
  • Phenol, acetaminophen (AA) and salicylamide are all known to be sulfated in rats and mice. We have previously demonstrated that capacity-limited sulfation of xenobiotics in rats is due to the reduced availability of hepatic 3'-phosphoadenosine 5'-phosphosulfate (PAPS), the cosubstrate for sulfation, which in turn is limited by the availability of its precursor, inorganic sulfate. Because species differences have been reported in the extent of sulfation, this study was conducted to determine whether these xenobiotics lower hepatic PAPS and sulfate in ICR mice. All three substrates decreased serum sulfate concentrations in a dose- and time-dependent manner. However, contrary to the observations in rats, phenol markedly increased hepatic PAPS concentrations in a dose-dependent manner, 1 hr after ip injection of 0∼4 mmol/kg. Following ip injection of 4 mmol/kg phenol, hepatic PAPS concentraions were enhanced 2∼3 fold, 0.5-2 hr after dosing and returned to control values 3 hr after dosing, whereas AA and salicylamide had little effect on hepatic PAPS concentraions. In summary, these studies demonstrate that phenol markedly enhances hepatic PAPS concentrations in mice, whereas hepatic PAPS levels are not affected by AA and salicylamide. Our data suggest that 1) hepatic sulfation for high dosages of xenobiotics in ICR mice is not limited by the availability of cosubstrate and 2) there are significant species differences in the regulation of PAPS between rats and mice.

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Korean pine nut oil replacement decreases intestinal lipid uptake while improves hepatic lipid metabolism in mice

  • Zhu, Shuang;Park, Soyoung;Lim, Yeseo;Shin, Sunhye;Han, Sung Nim
    • Nutrition Research and Practice
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    • v.10 no.5
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    • pp.477-486
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    • 2016
  • BACKGROUND/OBJECTIVES: Consumption of pine nut oil (PNO) was shown to reduce weight gain and attenuate hepatic steatosis in mice fed a high-fat diet (HFD). The aim of this study was to examine the effects of PNO on both intestinal and hepatic lipid metabolism in mice fed control or HFD. MATERIALS/METHODS: Five-week-old C57BL/6 mice were fed control diets containing 10% energy fat from either Soybean Oil (SBO) or PNO, or HFD containing 15% energy fat from lard and 30% energy fat from SBO or PNO for 12 weeks. Expression of genes related to intestinal fatty acid (FA) uptake and channeling (Cd36, Fatp4, Acsl5, Acbp), intestinal chylomicron synthesis (Mtp, ApoB48, ApoA4), hepatic lipid uptake and channeling (Lrp1, Fatp5, Acsl1, Acbp), hepatic triacylglycerol (TAG) lipolysis and FA oxidation (Atgl, Cpt1a, Acadl, Ehhadh, Acaa1), as well as very low-density lipoprotein (VLDL) assembly (ApoB100) were determined by real-time PCR. RESULTS: In intestine, significantly lower Cd36 mRNA expression (P<0.05) and a tendency of lower ApoA4 mRNA levels (P = 0.07) was observed in PNO-fed mice, indicating that PNO consumption may decrease intestinal FA uptake and chylomicron assembly. PNO consumption tended to result in higher hepatic mRNA levels of Atgl (P = 0.08) and Cpt1a (P = 0.05). Significantly higher hepatic mRNA levels of Acadl and ApoB100 were detected in mice fed PNO diet (P<0.05). These results suggest that PNO could increase hepatic TAG metabolism; mitochondrial fatty acid oxidation and VLDL assembly. CONCLUSIONS: PNO replacement in the diet might function in prevention of excessive lipid uptake by intestine and improve hepatic lipid metabolism in both control diet and HFD fed mice.

Inhibitory Effect of Injinchunggantang(Yinchenqinggan-tang) on Hepatic Sclerosis (인진청간탕(茵蔯淸肝湯)이 간보호(肝保護) 및 섬유화(纖維化) 억제(抑制)에 미치는 영향(影響))

  • Seung Hyun-Suk;Lee Jang-Hoon;Woo Hong-Jung;Kim Young-Chul
    • The Journal of Internal Korean Medicine
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    • v.24 no.1
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    • pp.21-32
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    • 2003
  • Objective : The aim of this study is to investigate the inhibitory effect of Injinchunggantang on hepatic sclerosis induced by $CCl_4$. Methods : Weight, liver function test and complete blood cell count, gross findings, and findings on liver tissue of the past(Hematoxylin & Eosin stain, Masson-Trichrome stain) were studied. Results : When it comes to the change of rats' body weight, The $CCl_{4^+}$Injinchunggantang group lost far less weight than The $CCl_{4^-}$only group. In the liver function test, which is focused on various areas such as total cholesterol, alkaline phosphotase, albumin, aspartate transaminase, alanine transaminase, The $CCl_{4^+}$Injinchunggantang group was much more closer to normal limit than the $CCl_4$ only group. In the complete blood cell count, including white blood cell, red blood cell, hemoglobin, hematocrite, platelet, The $CCl_{4^+}$Injinchunggantang group significantly closer to normal limit than $CCl_{4^-}$only group. In the gross findings of hepatic fibrosis models, Injinchunggantang showed inhibitory effect on hepatic fibrosis in the order. In the past findings of hepatic fibrosis models in Hematoxylin & Eosin, Masson-Trichrome staining, the liver in $CCl_{4^-}$only group showed atrophy and necrotic change with white nodules, whereas that of $CCl_{4^+}$Injinchunggantang group showed lesser significant change with the well_preserved tone of the tissue. In the extent of the inhibition of the hepatic fibrosis, the Injinchunggantang group showed statistically significant inhibitory effect(p<0.05) in the sclerosis model. Conclusions : These results show that Injinchunggantang have inhibitory effect on hepatic sclerosis induced by $CCl_4$ and further ultimately prevent liver cirrhosis. To obtain more credible results in this experiment, the invention of a new experimental model more similar to human hepatic sclerosis is still needed.

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Clinical Significance of the $^{99m}Tc-HIDA$ Cholescintigraphy in the Neonatal Jaundice (신생아 황달에서 $^{99m}Tc-HIDA$ 스캔의 임상적 의의)

  • Park, Nan-Jea;Kwon, In-Soon;Kwon, Jung-Sik;Kim, Myung-Duk;Lee, Myung-Chul;Cho, Bo-Yeon;Koh, Chang-Soon
    • The Korean Journal of Nuclear Medicine
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    • v.17 no.1
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    • pp.71-78
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    • 1983
  • Twenty-nine patients with neonatal jaundice were evaluated with $^{99m}Tc-HIDA$ cholescin-tigraphy to elucidate its clinical applicability. Scintigraphic results were interpreted by the degree of early hepatic uptake and the presence or absence of radioactivity in the G-I tract. The results are as follows; I) In 18 patents with neonatal hepatitis; 8 of 11 patients with decreased hepatic uptake and all 5 patients with good hepatic uptake showed G-I radioactivity. But, the 2 remainders with poor hepatic extraction were not available for evaluation of neonatal jaundice due to patient's poor hepatic function. 2) In 9 patients, confirmed as biliary obstruction; all showed no G-I radioactivity but 3 of the 9 showed poor hepatic extraction on scan and they were not available for evaluation. 3) All the 2 patients with postoperative cholangitis showed G-I radioactivity on $^{99m}Tc-HIDA$ scan. 4) Relationship between histopathologic findings and $^{99m}Tc-HIDA$ scan; Among 5 patients with biliary cirrhosis 3 showed poor hepatic extraction, the remainders showed decreased and good hepatic uptake respectively. But, the 2 portal fibrosis without cirrhosis and 4 cholestasis showed decreased (4) or good hepatic uptake (2).

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The Blood Disappearance Rate of $^{198}Au$-Colloid and Changes of Hepatic Blood Flow During Position Change in Normal Persons and in Patients with Various Hepatic Diseases (정상인(正常人) 및 각종(各種) 간질환(肝疾患) 환자(患者)에서 $^{198}Au$교질(膠質)의 혈중소실율치(血中消失率値)와 체위변동(體位變動)에 따른 간혈류량변화(肝血流量變化)에 관한 연구(硏究))

  • Cho, Bo-Yeon;Hong, Kee-Suck;Koh, Chang-Sun;Lee, Mun-Ho
    • The Korean Journal of Nuclear Medicine
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    • v.11 no.1
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    • pp.33-37
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    • 1977
  • To evaluate the diagnostic significance of the blood disappearance rate of $^{198}Au$-colloid and to evaluate the change of hepatic blood flow during position change from supine to erect, we measured the half time of blood disappearance rate of $^{198}Au$-colloid using external counting method in 94 normal persons and in 77 patients with various hepatic diseases. The results obtained were as follows: 1. In normal control, the mean blood disappearance half time of $^{198}Au$-colloid in supine position was $2.7{\pm}0.4$ minutes. There was no significant difference of hepatic blood flow in age and sex. 2. In acute hepatitis, chronic hepatitis and hepatic cirrhosis, the mean blood disappearance half times in supine position were $3.0{\pm}0.45,\;3.5{\pm}0.74,\;7.2{\pm}3.6$ minutes respectively. The hepatic blood flow of the patients with chronic hepatitis and hepatic cirrhosis were significantly decreased than that of normal control. 3. In the normal control and acute hepatitis, the decreaces of the hepatic blood flow during the position change from supine to erect were 27.7% and 22.6% respectively.

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Protective Effect of 6 Food Mixed-Extract on the CCl4-Induced Hepatic Damage in Rats (6종 식품의 혼합추출물이 사염화탄소로 유도된 흰쥐 간 손상에 미치는 보호효과)

  • Hwangbo, Mi-Hyang;Yea, Chun-Jung
    • The Korean Journal of Food And Nutrition
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    • v.31 no.6
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    • pp.828-835
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    • 2018
  • The objective of this study was to examine the biochemical parameters of hepatic function such as serum level of ALT (alanine aminotransferase), AST (aspartate aminotransferase), ALP (alkaline phosphatase), LDH (lactate dehydrogenase), and content of TG (triglyceride) and cholesterol, and tissue immunological changes of the $CCl_4$-treated rats with administration of the mixed sample extract (MSE). The liver weight in $CCl_4$-administered experimental control group (EC) was slightly higher than that of normal control (NC) group. Hepatic damage parameters (ALT, AST, ALP, LDH & TG) in serum of the EC group were significantly higher than those in serum of the NC and silymarin-treated positive control (PC) group. On the other hand, these hepatic damage parameters of MSE-treated experimental (E1 & E2) groups were significantly lower than those of EC group. The number of WBC, neutrophils, lymphocytes and platelets, and the contents of hemoglobin, and hematocrit in EC group were significantly higher than those of NC group. However, the number of WBC and lymphocytes in E1 and E2 groups were significantly lower than those of EC group. Also, the collagen developmental areas in the liver of NC and PC groups by hepatic immuno-histological findings were found slightly positive. Whereas, hepatic fibrous developmental tissue of EC group was strongly positive brown color band, those of E1 & E2 groups were decreased. Therefore, it was concluded that the induction of hepatic fibrous tissue activation had a preventive effect of MSE against the $CCl_4$-induced hepatic damage in rats. However, further study is needed in this filed.

ALTERATION OF HEPATIC 3′-PHOSPHOADENOSINE 5′_ PHOSPHOSULFATE(PAPS) AND SULFATE IN ICR MICE BY XENOBIOTICS THAT ARE SULFATED

  • Kim, H.J.;Oh, M.H.;Y.S.Sunwoo;Soe, K.W.;Moon, B.W.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.337-337
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    • 1994
  • Phenol, acetaminophen(AA) and salicylamide are all known to be sulfated in rats and mioe. We have previously demonstrated that capacity-limited sulfation of xenobiotics in rats is due to the reduced availability of hepatic PAPS, the co-substrate for sulfation, which in turn is limited by the availability of its precursor, inorganic sulfate. Because species differences have been reported in the extent of sulfation, this study was conducted to determine whether these xenobiotics lower hepatic PAPS and sulfate in ICR mice. All three substrates decreased serum sulfate concentrations in a dose-and time-dependent manner. However. contrary to the observations in rats, phenol markedly increased hepatic PAPS concentraions in a dose-dependent manner, 1 hr after ip injection of 0-4 mmol/kg. Following ip injection of 2 or4 mmol/kg phenol, hepatic PAPS concentraions were enhanced 2-3 fold, 0.52 hr arter dosing and returned to control values 3 hr after dosing, whereas AA and salicylamide had little effect on hepatic PAPS concentrations. In summary. these studies demonstrate that phenol markedly enhances hepatic PAPS concentrations in mice, whereas hepatic PAPS levels are not affected by AA and salicylamide. Our data suggest that 1) hepatic sulfation for high dosages of xenobiotics in ICR mice is not limiod by the availability of co-substrate, and 2) there are significant species differences in the regulation of PAPS between rats and mice.

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Influences of Guanethidine and ${\alpha}$-Methyl-para-tyrosine on the hepatotoxicity of Carbon tetrachloride ($CCL_4$의 간장독작용(肝臟毒作用)에 미치는 Guanethidine과 ${\alpha}$-Methyl-paratyrosine 의 영향(影響))

  • Kim, So-Kyung;Kim, Yang-Sook;Chun, Boe-Gwun
    • The Korean Journal of Pharmacology
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    • v.17 no.1 s.28
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    • pp.33-39
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    • 1981
  • In this paper, the influences of adrenergic neuronal blockades of different mode: guanethidine and ${\alpha}$-methyl-para-tyrosine on the changes induced by carbon tetrachloride $(CCl_4)$ of hepatic total lipid, glycogen, and lipid peroxide contents and serum lactic dehydrogenase activity were investigated in male mice. The results obtained were summarized as follows: 1) The hepatic total lipid and lipid peroxide contents and serum lactic dehydrogenase activity were markedly increased by $CCl_4$, but hepatic glycogen content were decreased. 2) The hepatic total lipid and lipid peroxide contents and serum lactic dehydrogenase activity were not significantly changed by guanethidine(20mg/kg) or ${\alpha}$-methyl-para-tyrosine (5 mg/kg) injection. 3) The increase of hepatic total lipid induced by $CCl_4$ was inhibited by the pretreatment of guanethidine or ${\alpha}$-methyl-para-tyrosine, and the increase of hepatic lipid peroxide content induced by $CCl_4$ was slightly inhibited by them. But the decrease of hepatic glycogen content and the increase of serum lactic dehydrogenase activity induced by $CCl_4$ were not affected by them.

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Development of Apoptosis Model and Bioimmune Responses and Morphological Characterization in Experimental Animal II. Activities of Serum Hepatic Enzyme and Histological Findings between Apoptosis and Hepatic Tumorigenesis (실험동물에서 apoptosis의 모델개발과 생체면역반응 및 형태학적 특징 II. Apoptosis 및 hepatic tumorigenesis 과정에서의 혈청 간 효소활성치 및 조직소견)

  • 강정부;하우송;곽수동;김지경
    • Journal of Veterinary Clinics
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    • v.16 no.1
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    • pp.108-117
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    • 1999
  • Hepatic tumorigenesis was induced by ad libitum feeding of diethylnitrosamine (DEN) only. We could also observe hepatic tumor induction in 100% of DEN treated rats without any other cocarcinogen. The liver specific enzyme activities (AST, ALT, ALP, ${\gamma}$-GTP) were significantly increased (P<0.05) in all treated groups compared to control and induced apoptosis groups. In histopathological analysis, the altered foci, hyperplastic nodules, neoplastic nodules, adenomas and carcinomas were observed in liver tumors induced by administration of DEN in rats. Lipopolysaccharide-induced apoptosis in D-galactosamine sensitized mice was investigated in hepatocytes in vivo. Typical morphological changes of apoptosis were detectable in liver 12 hr and 24 hr after the injection of Lipopolysaccharide (5 $\mu\textrm{g}$) and D-galactosamine (20 mg) to mice. It was suggested that organ specific enzyme activities and morphological findings might be very useful for understanding the role of hepatic tumorigenesis including the apoptotic cell death.

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Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on Acetaminophen-Induced Hepatic Damage in ICR Mice

  • Yi, Ruo-Kun;Song, Jia-Le;Lim, Yaung-Iee;Kim, Yong-Kyu;Park, Kun-Young
    • Preventive Nutrition and Food Science
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    • v.20 no.1
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    • pp.52-59
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    • 2015
  • This study was to investigate the preventive effect of taemyeongcheong (TMC, a Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC pretreatment also increased the hepatic levels of hepatic catalase, superoxide dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of the inflammatory cytokines tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA levels of TNF-${\alpha}$, IL-$1{\beta}$, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and 88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological observations suggested TMC pretreatment dose-dependently prevented APAP-induced hepatocyte damage. These results suggest that TMC could be used as a functional health drink to prevent hepatic damage.